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ANNUAL REPORT 2015 - 2016

USA Mitchell Cancer Institute Annual Report

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“The next several years offer us a unique opportunity to rise to become a world-class academic cancer center located on the beautiful Gulf Coast.” – Michael A. Finan, M.D.

Message from the Director Greetings, At USA Mitchell Cancer Institute, we continue to embrace growth and change as we advance our mission to vanquish cancer through transformative research, education and health care. This Annual Report provides a glimpse into new discoveries taking place in our research labs and highlights the people behind them. It introduces you to faculty members who are shaping key departments such as Radiation Oncology and Genetic Counseling. The report also includes an addendum of scholarly publications, demonstrating our drive to serve as the leading academic cancer institute in the region. As I meet with groups throughout the community, I am often asked, “What sets the Mitchell Cancer Institute apart in the field of health care?” The answer is simple: At MCI, we are not only cancer treatment providers. We are cancer researchers, professors, postdoctoral students and grant recipients. We are cancer caregivers, patient navigators and community transformers. Being part of an academic cancer institute requires that we embrace a variety of roles as we strive to improve the health of all people in our region. We believe that each experiment at the bench and each clinical trial bring us one step closer to a better understanding of cancer and new treatments for patients. This message echoes our country’s call for a “moonshot” to “cure cancer as we know it.” At MCI, we are proud to join the ranks of other academic cancer centers across the nation in answering that call. We invite you to join us in our mission as we serve the people of the upper Gulf Coast corridor. Sincerely,

Michael A. Finan, M.D. Director USA Mitchell Cancer Institute Annual Report

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Table of Contents Basic and Translational Sciences Published Journal Articles, Book Chapters, and Patents................................................................................. 2 Published Abstracts............................................................................................................................................ 8 Published Books.................................................................................................................................................14 Invited Presentations.........................................................................................................................................14 National Professional Recognition....................................................................................................................17 Brief Summary of Activities and Progress.......................................................................................................20

Gynecologic Oncology Published Journal Articles, Book Chapters and Patents................................................................................ 29 Abstracts (Presented at National Conferences)..............................................................................................31 Invited Presentations........................................................................................................................................34 National Professional Recognition...................................................................................................................34 Brief Summary of Activities and Progress ...................................................................................................... 35

Medical Oncology Published Journal Articles, Book Chapters, and Patents............................................................................... 38 Published Abstracts.......................................................................................................................................... 38 Invited Presentations........................................................................................................................................ 39 National Professional Recognition................................................................................................................... 39 Brief Summary of Activities and Progress....................................................................................................... 39

Radiation Oncology Published Journal Articles, Book Chapters, and Patents...............................................................................43 Published Abstracts..........................................................................................................................................43 National Professional Recognition...................................................................................................................44 Brief Summary of Activities and Progress.......................................................................................................44


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Summary of Scholarly Activities Basic and Translational Sciences


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“Cancer has touched all of us in some way. I decided I wanted to study cancer (either be an oncologist or a researcher) when my grandpa was diagnosed with multiple myeloma. I was young and had no idea what it meant, but watching him suffer made me realize that something needed to be done.” – Aishwarya Prakash, Ph.D., Assistant Professor of Oncologic Sciences

During 2016, we recruited new cancer researchers such as Dr. Aishwarya Prakash, left, and Dr. Marie Migaud, bringing the number of principal investigators to 15. We continue to make progress toward becoming an NCI-Designated Comprehensive Cancer Center with the University of Alabama at Birmingham by 2020. In addition, we established our Cancer Health Care Disparities Research Program to focus our research on overcoming the health disparities we see in our communities and across our region. Dr. Ajay Singh, professor of Oncologic Sciences, was named director of this important program. USA Mitchell Cancer Institute Annual Report

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I. PUBLISHED JOURNAL ARTICLES, BOOK CHAPTERS, AND PATENTS

Abadi A, Piazza GA. Mining ZINC database to discover potential phosphodiesterase 9 inhibitors using structure-based drug design approach. 2016 Published online, Medicinal Chemistry. PMID:26648332. Abdel-Rahman HM, Abdel-Aziz M, Tinsley HN, Gary BD, Canzoneri JC, Piazza GA. Design and synthesis of substituted pyridazinone-1-acetylhydrazones as novel phosphodiesterase 4 inhibitors. Arch Pharm Chem. Life Sci. 2016 348:1–8. PMID: 26686665. Ahmad A. Epigenetics in personalized management of lung cancer. Adv Exp Med Biol. 2016 890:111-22. Ali A, Ahmad A. Modulation of key signaling pathways in cancer cells by dietary factors. In: Ullah, MF, Ahmad, A, editors. Critical Dietary Factors in Cancer Chemoprevention. Springer; 2016 Chapter 13, p. 273-84. Arif H, Rehmani N, Farhan M, Ahmad A, Hadi SM. mobilization of copper ions by flavonoids in human peripheral lymphocytes leads to oxidative DNA breakage: A structure activity study. Int J Mol Sci. 2015; 16(11):26754-69. Arora S, Tyagi N, Bhardwaj A, Rusu L, Palanki P, Vig K, Singh SR, Singh AP, Palanki S, Miller ME, Carter JE, Singh S. Silver nanoparticles protect human keratinocytes against UVB radiation-induced DNA damage and apoptosis: potential for prevention of skin carcinogenesis. Nanomedicine. 2015; 11(5):1265–75. Azim S, Zubair H, Srivastava SK, Bhardwaj A, Zubair A, Ahmad A, Singh S, Khushman M, Singh AP. Deep sequencing and in silico analyses identify MYB-regulated gene networks and signaling pathways in pancreatic cancer. Sci Rep. 2016; 6:28446. doi: 10.1038/srep28446. Bhardwaj A, Srivastava SK, Singh S, Tyagi N, Arora S, Carter JE, Khushman M, Singh AP. myb promotes desmoplasia in pancreatic cancer through direct transcriptional up-regulation and cooperative action of sonic hedgehog and adrenomedullin. J Biol Chem. 2016; 291(31):16263-70. Chandran UR, Luthra S, Santana-Santos L, Mao P, Kim S-H, Minata M, Li J, Benos PV, DeWang M, Hu B, Cheng SY, Nakano I, Sobol RW. Gene expression profiling distinguishes proneural glioma stem cells from mesenchymal glioma stem cells. Genomics Data. 2015; 5:333-6; PubMed PMID: 26251826; PubMed Central PMCID: 4523279. Clark DW, Tripathi K, Dorsman JC, Palle K. FANCJ deficiency compromises the stability of FANCD2/ FANCI complex and promotes their degradation in a Caspase-3 mediated mechanism. Oncotarget. 2015; 6(30):28816-32. PMID:26336824. Daniel CL, Gilreath K, Keyes D. Colorectal cancer disparities beyond biology: Screening, treatment, access. Frontiers in Bioscience. 2017; 22:465-78. Daniel CL, Emmons KM, Fasciano K, Nevidjon B, Fuemmeler BF, Demark-Wahnefried W. Needs and lifestyle challenges of adolescents and young adults with cancer: summary of an Institute of Medicine workshop. Clinical Journal of Oncologic Nursing. 2015; 19(6):675-81.


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Deshmukh SK, Srivastava SK, Bhardwaj A, Singh AP, Tyagi N, Marimuthu S, Dyess DL, Dal Zotto V, Carter JE, Singh S. Resistin and interleukin-6 exhibit racially-disparate expression in breast cancer patients, display molecular association and promote growth and aggressiveness of tumor cells through STAT3 activation. Oncotarget. 2015; 6(13):11231-41. Fajardo A, Piazza GA. Chemoprevention in gastroenterological physiology and disease: Antiinflammatory approaches for colorectal cancer chemoprevention. American Journal of Physiology Gastrointestinal and Liver Physiology. 2015; 309:G59-70. doi 10.1152. PMID: 26021807. Farhan M, Khan HY, Oves M, Al-Harrasi A, Rehmani N, Arif H, Hadi SM, Ahmad A. cancer therapy by catechins involves redox cycling of copper ions and generation of reactive oxygen species. Toxins (Basel). 2016; 8(2):37. Gassman NR, Coskun E, Jaruga P, Dizdaroglu M, Wilson SH. Combined effects of high-dose bisphenol A and oxidizing agent (KBrO3) on cellular microenvironment, gene expression, and chromatin structure of Ku70-deficient mouse embryonic fibroblasts. Environ Health Perspect. 2016; 124(8):1241-52. Grabacka MM, Wilk A, Antonczyk A, Banks P, Walczyk-Tytko E, Dean M, Pierzchalska M, Reiss K. Fenofibrate induces ketone body production in melanoma and glioblastoma cells. Front Endocrinol (Lausanne). 2016; 7:5. doi: 10.3389/fendo. 2016.00005. eCollection 2016. Huang J, Eilbeck K, Smith B, Blake JA, Dou D, Huang W, Natale DA, Ruttenberg A, Huan J, Zimmermann MT, Jiang G, Lin Y, Wu B, Strachan HJ, He Y, Zhang S, Wang X, Liu Z, Borchert GM, Tan M. The Non-Coding RNA Ontology (NCRO): A comprehensive resource for the unification of non-coding RNA biology. J Biomed Semantics. 2016; 7:24. PubMed PMID: 27152146; PubMed Central PMCID: PMC4857245. Huang J, Gutierrez F, Strachan HJ, Dou D, Huang W, Smith B, Blake JA, Eilbeck K, Natale DA, Lin Y, Wu B, Silva N, Wang X, Liu Z, Borchert GM, Tan M, Ruttenberg A. OmniSearch: A semantic search system based on the Ontology for MIcroRNA Target (OMIT) for microRNA-target gene interaction data. J Biomed Semantics. 2016; 7:25. PubMed PMID: 27175225; PubMed Central PMCID: PMC4863347. Jin Y, Cai Q, Shenoy AK, Lim S, Zhang Y, Charles S, Tarrash M, Fu X, Kamarajugadda S, Trevino JG, Tan M, Lu J. Src drives the Warburg effect and therapy resistance by inactivating pyruvate dehydrogenase through tyrosine-289 phosphorylation. Oncotarget. 2016; 7(18):25113-24. doi: 10.18632/oncotarget.7159. [Epub ahead of print] PubMed PMID: 26848621. Kadri F, Pacifici M, Wilk A, Parker-Struckhoff A, Del Valle L, Hauser KF, Knapp PE, Parsons C, Jeansonne D, Lassak A, Peruzzi F. HIV-1-Tat protein inhibits SC35-mediated tau exon 10 inclusion through upregulation of DYRK1A kinase. J Biol Chem. 2015; 290(52):30931-46. Khan MA, Srivastava SK, Bhardwaj A, Singh S, Arora S, Zubair H, Carter JE, Singh AP. Gemcitabine triggers angiogenesis-promoting molecular signals in pancreatic cancer cells: therapeutic implications. Oncotarget. 2016; 6(36):39140-50. Kim JH, Shinde DN, Reijnders MR, Hauser NS, Belmonte RL, Wilson GR, Bosch DG, Bubulya PA, Shashi V, Petrovski S, Stone JK, Park EY, Veltman JA, Sinnema M, Stumpel CT, Draaisma JM, Nicolai J, University of Washington Center for Mendelian Genomics, Yntema HG, Lindstrom K, de Vries BB, Jewett T, Santoro SL, Vogt J, The Deciphering Developmental Disorders Study, Bachman KK, Seeley AH, Krokosky A, Turner C, Rohena L, Hempel M, Kortüm F, Lessel D, Neu A, Strom TM, Wieczorek D, Bramswig N, Laccone FA, Behunova J, Rehder H, Gordon CT, Rio M, Romana S, Tang S, El-Khechen D, Cho MT, McWalter


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K, Douglas G, Baskin B, Begtrup A, Funari T, Schoch K, Stegmann AP, Stevens SJ, Zhang DE, Traver D, Yao X, MacArthur DG, Brunner HG, Mancini GM, Myers RM, Owen LB, Lim ST, Stachura DL, Vissers LE, Ahn EY. De novo mutations in SON disrupt RNA-splicing of genes essential for brain development and metabolism, causing an intellectual disability syndrome. Am J Hum Genet. 2016; 99(3):711-9. http:// dx.doi.org/10.1016/j.ajhg.2016.06.029. Published online August 18. Kim JH, Baddoo MC, Park EY, Stone JK, Park H, Butler TW, Huang G, Yan X, Pauli-Behn F, Myers RM, Tan M, Flemington EK, Lim ST, Ahn EY. SON and its alternatively spliced isoforms control MLL complexmediated H3K4me3 and transcription of leukemia-associated genes. Mol Cell. 2016; 61:859-73. Klionsky DJ, Abdelmohsen K, Abe A, Abedin MJ, Abeliovich H, Tan M, et al (more than 500 names). Guidelines for the use and interpretation of assays for monitoring autophagy (3rd edition). Autophagy. 2016; 12(1):1-222. PubMed PMID: 26799652; PubMed Central PMCID: PMC4835977. Kothayer H, Spencer S, Tripathi K, Westwell AD, Palle K. Synthesis and in vitro anticancer evaluation of some 4,6-diamino1,3,5triazine-2-carbohydrazides as Rad6 Ubiquitin conjugating enzyme inhibitors. Bioorganic and Medicinal Chemistry Letters. 2016; 26(8):2030-4. PMID: 26965855; PMCID: PMC4808444. Lee K, Lindsey A, Li N, Gary B, Andrews J, Keeton A, Piazza GA. β-catenin nuclear translocation in colorectal cancer cells is suppressed by PDE10A inhibition, cGMP elevation, and activation of PKG. Oncotarget. 2016; 7:5353-65. PMID: 26713600. Li N, Chen X, Zhu B, Ramírez-Alcántara V, Canzoneri JC, Lee K, Sigler S, Gary B, Li Y, Zhang W, Moyer MP, Salter EA, Wierzbicki A, Keeton A, Piazza GA. Suppression of β-catenin/TCF transcriptional activity and colon tumor cell growth by dual inhibition of PDE5 and 10. Oncotarget. 2015; 6:27403-15. PMID: 26299804. Lim S, Liu H, Madeira da Silva L, Arora R, Liu Z, Phillips JB, Schmitt DC, Vu T, McClellan S, Lin Y, Lin W, Piazza GA, Fodstad O, Tan M. Immunoregulatory protein B7-H3 reprograms glucose metabolism in cancer cells by ROS-mediated stabilization of HIF1α. Cancer Res. 2016; 76(8):2231-42. doi: 10.1158/0008-5472.CAN-15-1538. Epub 2016 Apr 5. PubMed PMID: 27197253; PubMed Central PMCID: PMC4874665. Lim S, Liu H, Madeira da Silva L, Arora R, Liu Z, Phillips JB, Schmitt DC, Vu T, McClellan S, Ling Y, Lin W, Piazza GA, Fodstad O, Tan M. The immunoregulatory protein B7-H3 regulates reprogramming of cancer cell glucose metabolism through reactive oxygen species mediated stabilization of HIF-1. Cancer Research. 2016; 15:2231-42. PMID:27197253. Lim S, Smith KR, Lim ST, Tian R, Lu J, Tan M. Regulation of mitochondrial functions by protein phosphorylation and dephosphorylation. Cell Biosci. 2016; 6:25. PubMed PMID: 27087918; PubMed Central PMCID: PMC4832502. Liu Y, Zhao R, Wang H, Luo Y, Wang X, Niu W, Zhou Y, Wen Q, Fan S, Li X, Xiong W, Ma J, Li X, Tan M, Li G, Zhou M. miR-141 is involved in BRD7-mediated cell proliferation and tumor formation through suppression of the PTEN/AKT pathway in nasopharyngeal carcinoma. Cell Death Dis. 2016; 7:e2156. doi: 10.1038/cddis.2016.64. PubMed PMID:27010857; PubMed Central PMCID: PMC4823963. Ma R, Yi B, Piazza GA, Xi Y. Mechanistic role of microRNA in cancer chemoprevention by nonsteroidal anti-inflammatory drugs. Curr Pharmacol Rep. 2015; 1:154-60. PMID: 26213681.


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McClellan S, Slamecka J, Howze P, Thompson L, Finan M, Rocconi R, Owen L. mRNA detection in living cells: A next generation cancer stem cell identification technique. Methods. 2015; 82:47-54. Epub 2015 Apr 25. PMID: 25920950. Nunes-Xavier CE, Karlsen KF, Tekle C, Pedersen C, Øyjord T, Hongisto V, Nesland JM, Tan M, Sahlberg KK, Fodstad Ø. Decreased expression of B7-H3 reduces the glycolytic capacity and sensitizes breast cancer cells to AKT/mTOR inhibitors. Oncotarget. 2016; 7(6):6891-901. doi: 10.18632/oncotarget.6902. PubMed PMID: 26771843; PubMed Central PMCID: PMC4872756. Palle K, Mani C, Tripathi K, Athar M. Aberrant GLI1 activation in DNA damage response, carcinogenesis and chemoresistance. Cancers. 2015; 7:2330-52. (invited review), PMID: 26633513; PMCID: PMC4695894. Patel G, Patton M, Singh S, Khushman M, Singh AP. Pancreatic cancer exosomes: shedding-off for a meaningful journey. Pancreatic disorders & Ther. 2016; 6(2):e148. Prakash A, Cao VB, Doublié S. Phosphorylation sites identified in NEIL1 are sites for the JNK1 kinase. Plos One. 2016; 11(8):e0157860. Co-Corresponding Author. Rani V, Deep G, Singh RK, Palle K, Yadav UCS. Oxidative stress in metabolic disorders: Pathogenesis, prevention, and therapeutics. Life Sciences. 2016; 148:183-93. PMID: 26851532 (Invited review). Rocker JM, Tan M, Thompson LW, Contreras CM, Pannell LK. Comparative proteomic analysis of wholegut lavage fluid and pancreatic juice reveals a less invasive method of sampling pancreatic secretions. Clin Trans Gastroenterol. 2016; 7:174-81. PMID: 27228405. Rezk MS, Abdel-Halim M, Keeton AB, Franklin D, Boeckler FM, Engel M, Hartmann RW, Zhang Y, Piazza GA, Abadi AH. Synthesis and optimization of new 3,6-disubstituted indole derivatives and their evaluation as anticancer agents targeting the MDM2/MDMx complex. Chem Pharm Bull. 2015; 64:34– 41. PMID: 26726742. Sawant A, Kothandapani A, Zhitkovich A, Sobol RW, Patrick SM Role of mismatch repair proteins in the processing of cisplatin interstrand cross-links. DNA Repair. 2015; 35:126-36; PubMed PMID: 26519826; PubMed Central PMCID:4651805. Schmitt D, Andrews J, Tan M. Determination of breast cancer cell migratory ability. Methods Mol Biol. 2016; 1406:171-80. PubMed PMID: 26820954. Shen JP, Srivas R, Gross A, Li J, Jaehnig EJ, Sun SM, Bojorquez-Gomez A, Licon K, Sivaganesh V, Xu JL, Klepper K, Yeerna H, Pekin D, Qiu CP, Attikum H, Sobol RW, Ideker T. Chemogenetic profiling identifies RAD17 as synthetically lethal with checkpoint kinase inhibition. 2015 Oncotarget. 2015; 6(34):35755-69; PubMed PMID:26437225; PubMed Central PMCID:4742139. Slamecka J, Salimova L, McClellan S, van Kelle M, Kehl D, Laurini J, Cinelli P, Owen L, Hoerstrup SP, Weber B. Non-integrating episomal plasmid-based reprogramming of human amniotic fluid stem cells into induced pluripotent stem cells in chemically defined conditions. Cell Cycle. 2016; 15(2):234-49,. PMID: 26654216. Somasagara RR, Tripathi K, Spencer SM, Clark DW, Barnett R, Bachaboina L, Scalici J, Rocconi RP, Piazza GA, Palle K. Rad6 upregulation promotes stem cell-like characteristics and platinum resistance in ovarian cancer. Biochem Biophy Res Comm. 2016; 469:449-55. PMID: 26679603.


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Somasagara RS, Tripathi K, Spencer SM, Clark DW, Barnett R, Bachaboina L, Scalici J, Rocconi RP, Piazza GA, Palle K. Rad6 upregulation promotes stem cell-like characteristics and platinum resistance in ovarian cancer. Biochem Biophy Res Commun. 2016; 469;449-55. PMID: 26679603; PMCID: PMC4715924. Srivas R, Shen JP, Yang CC, Sun SM, Li J, Gross AM, Jensen J, Licon K, Bojorquez-Gomez A, Klepper K, Huang J, Pekin D, Xu JL, Yeerna H, Sivaganesh V, Kollenstart L, van Attikum H, Aza-Blanc P, Sobol RW, Ideker T. A network of conserved synthetic lethal interactions for exploration of precision cancer therapy. Molecular Cell. 2016; 63(3):514-25; PubMed PMID:27453043; PubMed Central PMCID: n/a. Srivastava SK, Bhardwaj A, Singh S, Arora S, Azim S, Tyagi N, Carter JE, Wang B, Singh AP. MYB is a novel regulator of pancreatic tumor growth and metastasis. Br J Cancer. 2015; 113(12):1694-703. Srivastava SK, Bhardwaj A, Arora S, Azim S, Tyagi N, Singh S, Andrews J, McClellan, S, Wang B, Singh AP. MicroRNA-345 induces apoptosis in pancreatic cancer cells through potentiation of caspase -dependent and -independent pathways. Br J Cancer. 2015; 113(4):660-8. Srivastava SK, Bhardwaj A, Arora S, Tyagi N, Singh AP, Carter JE, Scammell JG, Fodstad Ø, Singh S. Interleukin-8 is a key mediator of fkbp51- induced melanoma growth, angiogenesis and metastasis. Br J Cancer. 2015; 112(11):1772-81. Srivastava SK, Arora S, Averett C, Singh S, Singh AP. Modulation of microRNAs by phytochemicals in cancer: Underlying mechanisms and translational significance. Biomed Res Int. 2015; 2015:848710. Tang X, Jin L, Cao P, Cao K, Huang C, Luo Y, Ma J, Shen S, Tan M, Li X, Zhou M. MicroRNA-16 sensitizes breast cancer cells to paclitaxel through suppression of IKBKB expression. Oncotarget. 2016; 7(17):23668-83. doi:10.18632/oncotarget.8056. PubMed PMID: 26993770. Tripathi K, Hussein UK, Anupalli R, Barnett R, Bachaboina L, Scalici J, Rocconi RP, Owen LB, Piazza GA, Palle K. Allyl isothiocynate induces replication-associated DNA damage response in NSCLC cells and sensitizes to ionizing radiation. Oncotarget. 2015; 6:5237-52. PMID: 25742788. Tripathi K, Hussein UK, Anupalli R, Barnett R, Bachaboina L, Scalici J, Rocconi RP, Owen LB, Piazza GA, Palle K. Allyl isothiocyanate induces replication-associated DNA damage response in NSCLC cells and sensitizes to ionizing radiation. Oncotarget. 2015; 6(7):5237-52; PMID: PMID:25742788; PMCID: PMC4467145. Tripathi K, Mani C, Clark D, Barnett R, Palle K. Rad18 is required for functional interactions between FANCD2, BRCA2, and Rad51 to repair DNA topoisomerase 1-poisons induced lesions and promote fork recovery. Oncotarget. 2016; 7(11):12537-53. PMID: 26871286. Tyagi N, Bhardwaj A, Srivastava SK, Arora S, Marimuthu S, Deshmukh SK, Singh AP, Carter JE, Singh S. Development and characterization of a novel in vitro progression model for UVB-induced skin carcinogenesis. Sci Rep. 2015; 5:13894. Tyagi N, Marimuthu, S, Bhardwaj A, Deshmukh SK, Srivastava SK, Singh AP, McClellan S, Carter JE, Singh S. p-21 activated kinase 4 (PAK4) maintains stem cell-like phenotypes in pancreatic cancer cells through activation of STAT3 signaling. Cancer Lett. 2016; 370(2):260-7. Wang H, Zhao R, Guo C, Jiang S, Yang J, Xu Y, Liu Y, Fan L, Xiong W, Ma J, Peng S, Zeng Z, Zhou Y, Li X, Li Z, Li X, Schmitt DC, Tan M, Li G, Zhou M. Knockout of BRD7 results in impaired spermatogenesis and male infertility. Sci Rep. 2016; 6:21776. doi: 10.1038/srep21776. PubMed PMID:26878912; PubMed Central PMCID: PMC4754950. USA Mitchell Cancer Institute Annual Report

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Wang J, Qian W, Li J, Santana-Santos L, Shuda M, Sobol RW, Van Houten B. A novel strategy for targeted killing of tumor cells: induction of multipolar acentrosomal miotic spindles with a quinazolinone derivative mdivi-1. Mol Oncol. 2015; 9(2):488-502. doi: 10.1016/j.molonc. 2014.10.002. Epub 2014 Oct 17. PubMed PMID: 25458053; PubMed Central PMCID: PMC4305024. Wendell SG, Golin-Bisello F, Wenzel S, Sobol RW, Holguin F, Freeman BA. 15-hydroxyprostaglandin dehydrogenase generation of electrophilic lipid signaling mediators from hydroxy omega-3 fatty acids. J Biol Chem. 2015; 290(9):5868-80. pii: jbc.M114.635151. PubMed PMID: 25586183; PubMed Central PMCID: PMC4342494. Whitt J, Keeton A, Sklar L, Chen X, Piazza GA. Sulindac sulfide selectively increases sensitivity of ABCC1 expressing tumor cells to doxorubicin and glutathione depletion. Published online, J Biomed Res. 2016. doi:10.7555/JBR.30.20150108. Xin W, Feinstein WP, Ochoa CD, Britain AL, Zhu B, Richter W, Leavesley SJ, Rich TC. Estimating the magnitude of near-membrane PDE4 activity in living cells. Am J Physiol Cell Physiol. 2015; 309:C415-24. Yi B, Chang B, Feng X, Ma R, Piazza GA, Xi Y. A novel sulindac derivative inhibits breast cancer metastasis through suppression of TGFβ/miR-21 signaling. Oncotarget. 2016; 16:7979-92. PMID:26769851. Yuzefovych LV, Kahn AG, Schuler MA, Eide L, Arora R, Wilson GL, Tan M, Rachek LI. Mitochondrial DNA repair through OGG1 activity attenuates breast cancer progression and metastasis. Cancer Res. 2016; 76(1):30-4. PubMed PMID: 26586787; NIHMSID: NIHMS734184; PubMed Central PMCID: PMC4703513. Zea AH, Stewart T, Ascani J, Tate DJ, Finkel-Jimenez B, Wilk A, Reiss K, Smoyer WE, Aviles DH. Activation of the IL-2 receptor in podocytes: A potential mechanism for podocyte injury in idiopathic nephrotic syndrome? PLoS One. 2016; 11(7):e0157907. doi:10.1371/journal.pone.0157907. eCollection 2016. Zeng Z, Fan S, Zhang X, Li S, Zhou M, Xiong W, Tan M, Zhang W, Li G. Epstein-Barr virus-encoded small RNA 1 (EBER-1) could predict good prognosis in nasopharyngeal carcinoma. Clin Transl Oncol. 2016; 18(2):206-11. PubMed PMID: 26260913. Zhao R, Liu Y, Wang H, Yang J, Niu W, Fan S, Xiong W, Ma J, Li X, Phillips JB, Tan M, Qiu Y, Li G, Zhou M. BRD7 plays an anti-inflammatory role during early acute inflammation by inhibiting activation of the NF-кB signaling pathway. Cell Mol Immunol. 2016. doi:10.1038/cmi.2016.31. PubMed PMID: 27374794. Zubair H, Azim S, Khan HY, Ullah MF, Wu D, Singh AP, Hadi SM, Ahmad A. Mobilization of intracellular copper by gossypol and apogossypolone leads to reactive oxygen species-mediated cell death: Putative anticancer mechanism. Int J Mol Sci. 2016; 17(5)pii: E973.


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Published Book Chapters Keeton AB, Piazza GA. Search for Inhibitors of Ras-Driven Cancers. In: Azmi A, Conquering RAS. Cambridge: Elsevier Inc. August 2016. Khan MA, Zubair H, Srivastava SK, Singh S, Singh AP. Insights into the Role of microRNAs in Pancreatic Cancer Pathogenesis: Potential for Diagnosis, Prognosis, and Therapy. In: Gaetano Santulli, editor. microRNA: Cancer. New York; Springer Publications; 2015. Chapter 5, p. 71-87. Zubair H, Azim S, Srivastava SK, Bhardwaj A, Marimuthu S, Patton MC, Singh S, Singh AP. In: Saura C Sahu, editor. microRNA: Stem Cells in Toxicology and Medicine. : Wiley Publications; 2016. Chapter 20, p. 375-413

Patents Piazza GA, Chen X, Keeton AB, Boyd MR. Indenyl compounds, pharmaceutical compositions, and medical uses thereof. U.S. Patent Application No. 14/571617, Published 2016. Piazza GA, Chen X, Keeton AB, Boyd MR. Methods of treating or preventing Ras-mediated diseases. U.S. Patent Application No. 14/571,690, Published 2016. Piazza GA, Chen X, Keeton AB, Boyd MR. Ras-inhibiting indenyl acetamide compounds, compositions, and uses. PCT/U.S. Patent Application No. 14/70511, Published 2016. Piazza GA, Chen X, Keeton AB, Boyd MR. Compounds, compositions, and methods of treating Rasmediated diseases. U.S. Patent Application No. 62/092,491, Published 2016. Piazza GA, Chen X, Keeton AB, Boyd MR. Ras inhibitory indole compound, composition, and method of treatment. U.S. Patent Application No. 62/092,498, Published 2016.

II. PUBLISHED ABSTRACTS Andrews J, Dey N, Wilk A, Sobol RW. PARP1-Mediated Nuclear to Mitochondrial Communication. (2015) Environmental and Molecular Mutagenesis; v56, S60-S60. Arora S, Tyagi N, Srivastava SK, Carter JE, Singh AP, Singh S. Preclinical evaluation of chemopreventive efficacy of silver nanoparticles against ultraviolet radiation-induced skin carcinogenesis. NanoBio Summit, University of Alabama at Birmingham; 2015, Oct 15 -16. Averett C, Bhardwaj A, Arora S, Srivastava SK, Carter JE, Singh S, Singh AP. Studies on the Anticancer Activities of Honokiol in Pancreatic Cancer. Fourth AACR International Conference on Frontiers in Basic Cancer Research, October 23-26, 2015, Philadelphia, PA.


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Bhardwaj A, Srivastava SK, Tyagi N, Arora S, Singh S, Carter JE, Singh AP. MYB promotes pancreatic tumor associated-desmoplasia by up-regulating Sonic hedgehog and adrenomedullin. Cancer Res. 2016; 76:722. Clark JE, Fang Q, Zeng X, Yates NA, Sobol RW. Differentiating Pol beta and Pol beta/XRCC1 Repair Protein Complexes Using a Promiscuous Biotin Ligase Fusion System. 2015 Environmental and Molecular Mutagenesis; v56 S65-S65. Clark DW, Tripathi K, Mani C, Palle K. FANCJ/BRIP1 is important for eliciting DNA damage responses and repair of DNA topoisomerase I poisons induced replication-associated DNA damage. DNA Topoisomerases in Biology & Medicine Gordon Research Conference. August 7-12, 2016, Sunday River, Newry, ME. Colomb WD, Tan M, Tang W, Ambs S, Yates C. Abstract P5-08-38: Low lactate dehydrogenase B expression correlates with decreased distant-metastasis free- and recurrence-free survival postchemotherapy in basal-like breast cancer. Cancer Res February 2016, 76(4 Suppl) P5-08-38-P5-08-38; DOI:10.1158/1538-7445.SABCS15-P5-08-38. Daniel CL, Otto JJ, Rocker JM, Schambeau LN, Pannell LK. Glycopeptide Analysis Using Parallel DataDependent Acquisition at Varied Normalized Collision Energies. Proceedings of the American Society for Mass Spectrometry Annual Meeting; June 5-9, 2016, San Antonio, TX. Desai S, Tan M. Abstract B55: Role of HSF1 in chemotherapy-induced autophagy and endoplasmic reticulum stress response in breast cancer. Molecular Cancer Research 14(1 Suppl):B55-B55, January 2016. DOI: 10.1158/1557-3125.METCA15-B55. Fang Q, Brown AR, Wang X, Sobol RW. Altered Mechanisms of Stability for Somatic Mutants of DNA Polymerase beta. 2015 Environmental and Molecular Mutagenesis; v56, S59-S59. Gassman NR, Coskun E, Jaruga P, Dizdaroglu M, Wilson SH. BPA alters cellular microenvironment to promote cell survival after oxidative stress. In: 2016 Annual Meeting Abstract Supplement, Society of Toxicology, 2016. Abstract no. 1390. Huang J, Eilbeck K, Blake JA, Dou D, Natale A, Ruttenberg A, Smith B, Zimmermann MT, Jiang G, Lin Y, Wu BH, Yongqun Z, Shaojie W, Xiaowei Z, Zixing L, Tan M. Conference Paper: A domain ontology for the Non-Coding RNA field. November 2015 Conference: 2015 IEEE International Conference on Bioinformatics and Biomedicine (BIBM), DOI: 10.1109/BIBM.2015.7359755. Kay J, Saki M, Sharma N, Prakash A. A two-prong approach to obtaining constructs of NEIL2 for downstream crystallization applications. College of Medicine Summer Medical Student Research Program; July 28, 2016, Mobile, AL. Keeton AB, Zhu BL, Canzoneri K, Joshua C, Sigler SC, Lindsey AS, Ramirez-Alcantara V, Barnes L, Mattox TE, McConnell K, Berry KL, Valiyaveettil J, Chen X, Boyd MR, Piazza GA. Discovery and in vitro and in vivo characterization of a novel, small-molecule Ras inhibitor class. Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; Apr 16-20, 2016, New Orleans, LA. Abstract 326. Khan MA, Srivastava SK, Bhardwaj A, Singh S, Carter JE, Singh AP. Gemcitabine triggers angiogenesispromoting molecular signals in pancreatic cancer cells: Therapeutic implications. Cancer Res 2015; 75:4182.


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Khushman M, Bhardwaj A, Patel GK, Laurini JA, Roveda R, Tan M, Singh S, Taylor W, Singh AP. The Pattern of Exosomal Marker (CD63) Expression Using Immunohistochemistry (IHC) in Malignant and Non-malignant (normal, inflammatory and pre-malignant) Ductal Cells in Resected Pancreatic Tissues. 2016 Pancreatic Cancer: Advances in Science and Clinical Care May 12-15, 2016, Orlando, FL. Khushman M, Hosein PJ, Cameron D, Clarkson DR, Butler TW, Vu MA, Norden CW, Baliem W, Jones V, Bhadkamkar S, Nelson C, Lee F, Singh AP, Taylor WR (2016) Germline pharmacogenomics in patients with dihydropyrimidine dehydrogenase (DPD) deficiency. ASCO 2016 Gastrointestinal Cancers Symposium January 21-23, 2016. Khushman M, Patel GK, Bhardwaj A, Srivastava SK, Khan MA, Singh S, Brandt B, Taylor WR, Singh AP. The Role of Exosomes in Promoting Acquired Resistance to Gemcitabine and Nanoparticle AlbuminBound (NAB) Paclitaxel in Pancreatic Ductal Adenocarcinoma Cells. 2016; ASCO Annual Meeting, June 3-7 June 2016, Chicago, IL. Kim JH, Butler TW, Ahn EY. SON and its alternatively spliced isoforms control MLL complex-mediated H3K4me3 and transcription of leukemia-associated genes. Blood 2015; 126:2426. Kim JH, Park EY, Stone JK, Butler TW, Ahn EY. SON and its splice variants regulate MLL1/2 complexmediated H3K4me3 and transcription of leukemia-associated genes. Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; Apr 16-20, 2016, New Orleans, LA. Cancer Research 2016; 76(14 Supplement):1978. Abstract no. 1978. Lassak A, Wyczechowska D, Wilk A, Zapata A, Dean M, Del Valle L, Sarkaria JN, Ochoa A, Peruzzi F, Reiss K. IRS-1/LC3 nuclear structures and glioblastoma drug resistance. Cancer Research. 2016; 76(14 Suppl):2520. Abstract no. 2520. Laurini AJ, Khushman M, Bhardwaj A, Patel GK, Roveda KP, Tan M, Singh S, Taylor W, Singh AP. Exosomal Markers (CD63 and CD9) Expression by Immunohistochemistry (IHC) in Pancreatectomy Specimens (PS). XXXI International Congress of the IAP and 28th Congress of the ESP, Cologne, Germany, Sept 25-29, 2016. Lee K, Chen X, Valiyaveettil J, Lindsey AS, Andrews J, Ramirez-Alcantara V, Keeton AB, Piazza GA. Clapper M, Chang W-C. Novel non-COX inhibitory sulindac derivative with PDE10 inhibitory activity reduces incidence and multiplicity of colon tumors in the APCmin mouse model. American Association for Cancer Research Colorectal Cancer: Conference: Sept 17-20, 2016, Tampa, FL. Lee KJ, Lindsey AS, Madeira da Silva L, Trinh A, Bernard G, Andrews J, Ramirez-Alcantara V, Keeton AB, Chang W-C, Clapper M, Piazza GA. Beta-catenin nuclear translocation in colorectal cancer cells is suppressed by PDE10A inhibition, cGMP elevation, and activation of PKG. Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; Apr 16-20, 2016, New Orleans, LA. Abstract 331. Li J, Svilar D, Inanc B, Gibson SP, Ferris RL, Vens C, Sobol RW. Quantitative, Real-time Analysis of Base Excision Repair Activity Using Lesion-Specific Molecular Beacons. (2015) Environmental and Molecular Mutagenesis; v56, S67-S67. Lim SL, Hao B, Barnes Luciana, Tan, M. Abstract 48: The immunoregulatory protein B7-H3 regulates reprogramming of cancer cell glucose metabolism through reactive oxygen species mediated stabilization of HIF-1α. Cancer Research 2016; 76(14 Suppl):48. DOI: 10.1158/1538-7445.AM2016-48.


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Lindsey AS, Lee K, Andrews J, Chang W-C, Ramirez-Alcantara V, Tan M, Clapper M, Piazza GA. PDE10A overexpression in colon cancer cells and tumors as compared to normal colonocytes and colon mucosa. American Association for Cancer Research Colorectal Cancer: Conference: Sept 17-20, 2016, Tampa FL. Lindsey A, Lee S, Zhu K, Arora R, Otali D, Ramirez-Alcantara V, Grizzle W, Piazza GA. PDE10A overexpression in cancer cells and tumors as compared to normal cells and tissues. Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; Apr 16-20, 2016, New Orleans, LA. Abstract 4736. Lormand J, Fouquerel E, Freudenthal B, Sobol RW, Myong S, Opresko PL. Investigating How Oxidative DNA Damage Influences Telomere Maintenance. 2015 Environmental and Molecular Mutagenesis; v56, S50-S50. Madeira da Silva L, Scalici JM, McClellan S, Laurini J, Cruthirds L, Kolev V, Li Y, Shapiro IM, Weaver D, Rocconi RP. Standard chemotherapy for ovarian cancer increases expression of cancer stem cell biomarkers which is predictive of survival. 47th Annual Meeting of the Society of Gynecologic Oncology; Mar 19-22, 2016, San Diego, CA. p. 48-49. Abstract no. 67. Mani C, Tripathi K, Vindgini A, Palle K. A novel nuclear role for trans-golgi network protein PACS-1 in suppression of replication stress in tumor cells. At the Intersection of DNA replication and Genome Maintenance: from Mechanism to Therapy. June 27-July 1, 2016, Trieste, Italy. Nunes-Xavier CE. Karlsen KF, Øyjord T, Tan M, Fodstad, Ø. Abstract 4133: Suppressed B7-H3 expression reduces glycolytic capacity and sensitizes tumor cells to anti-cancer agents. Cancer Res. 2016; 76(14 Suppl):4133. DOI:10.1158/1538-7445. Omar Y, Arora S, Tyagi N, Srivastava SK, Rusu L, Tambe DT, Palanki S, Singh AP, Carter JE, Singh S. Comparative study on the protective efficacy of silver, zinc oxide and titanium dioxide nanoparticles in human keratinocytes against UVB radiation-induced DNA damage. NanoBio Summit, University of Alabama at Birmingham; Oct 15-16, 2015. Otto JJ, Daniel CL, Schambeau LN, Rocker JM, Pannell LK. Quantitation of Immunoglbulin Alpha from Whole Gut Lavage Fluid Using the Thermo Q-Exactive Plus. Proceedings of the American Society for Mass Spectrometry Annual Meeting; June 5-9, 2016, San Antonio, TX. Patel M, Bachaboina L, da Silva LM, Bae Sejong, Rocconi RP, Palle K, Scalici JM. The Good, the bad, and the Ugly: Estrogen Metabolism and Endometrial Cancer Risk. Society for Gynecological Oncology 2016. Patel GK, Bhardwaj A, Srivastava SK, Khan MA, Singh S, Khushman M, Singh AP. Chemotherapyinduced exosomal secretion promotes chemoresistance in pancreatic cancer cells. Cancer Res 2016; 76:2116. Pednekar V, Gassman NR. Effects of low-dose BPA on cellular microenvironment: a comparative study of normal and human cancer cells. In: 47th Annual Meeting Program, Environmental Mutagenesis and Genomics Society, Sept 24-28, 2016, Kansas City, MO. Abstract no. 63. Phillips J, Kim JH, Lim S, Ahn E, Tan M. Abstract 1996: Regulation of RNA splicing of the ErbB family receptors by the splicing cofactor SON. Cancer Res 2016; 76(14 Supplement):1996. DOI:10.1158/15387445.


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Phillips J, Kim JH, Lim S, Ahn EY, Tan M. Regulation of RNA splicing of the ErbB family receptors by the splicing cofactor SON. Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; Apr 16-20, 2016, New Orleans, LA: AACR; Cancer Res 2016; 76(14 Suppl):1996. Abstract no. 1996. Piazza GA, Zhu B, Lee K, Canzoneri J, Sigler S, Lindsey, Ramirez-Alcantara V, Barnes L, Mullins H, Trinh A, Berry K, Valiyaveettil J, Keeton AB, Xi C, Boyd MR. Novel drug development candidate potently and selectively inhibits growth of tumor cells harboring activated Ras. Proceedings of AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics; Nov. 6-9, 2015, Boston, MA. Prakash A, Moharana K, Averill A, Wallace S, Doublié S. Destabilization of the PCNA trimer mediated by interaction with NEIL1 and DNA. Gordon Research Conference Mutagenesis; June 5–10, 2016, Girona, Spain. p. 11. Abstract no. 42. Ramirez-Alcantara V, Keeton AB, Zhu B, Lee K, Canzoneri J, Lindsey AS, Madeira da Silva Barnes L, Berry K, Valiyaveettil J, Chen X, Boyd MR, Piazza GA. DC070-547, a novel Ras inhibitor potently and selectivity inhibits colon tumor growth in vitro and in vivo. American Association for Cancer Research Colorectal Cancer: Conference: Sept 17-20, 2016, Tampa FL. Rocker JM, Schambeau LN, Pannell LK. Challenges and Solutions When Using OpenMS LFQProfiler Node in Proteome Discoverer 2.1 for Feature Comparisons in Very Large Datasets. Proceedings of the American Society for Mass Spectrometry Annual Meeting; June 5-9, 2016, San Antonio, TX. Ross JG, Braswell KV, Scalici JM, Madeira da Silva L, Mujica F, Stutsman S, Nicolson W, Harmon MD, Boudreau S, Wang B, Finan MA, Rocconi RP. Unraveling the etiology of ovarian cancer racial disparity in the Deep South: Is it nature or nurture? 47th Annual Meeting of the Society of Gynecologic Oncology; Mar 19-22, 2016, San Diego, CA. p. 192-193. Abstract no. 268. Saki M, Makino H, Tomimatsu N, Ding L, Story MD, Burma S, Nirodi C: Activating mutations in EGFR abrogate hypoxia-associated radiation resistance in non-small cell lung cancer. Cancer Res. 2016; 76(14 Suppl):523. Scalici JM, Ross JG, Madeira da Silva L, Nicolson W, Harmon MD, Boudreau S, Wang B, Finan MA, Rocconi RP. Evaluating racial molecular complexity in gynecologic cancers. 47th Annual Meeting of the Society of Gynecologic Oncology; Mar 19-22, 2016, San Diego, CA. p. 198. Abstract no. 275. Spencer SM, Somasagara RR, Tripathi K, Bachaboina L, Scalici J, Rocconi RP, Palle K. Rad6 inhibition sensitizes ovarian cancer cells to platinum drugs by attenuating activation of multiple DNA repair networks. Society for Gynecological Oncology 2016. Stone J K, Kim JH, Tan M, Ahn E. Abstract 1835: NFATC1 regulates the long non-coding RNA MALAT1 in breast cancer. Cancer Res July 2016, 76(14 Suppl): 1835; DOI:10.1158/1538-7445. Stone JK, Kim JH, Tan M, Ahn EY. NFATC1 regulates the long non-coding RNA MALAT1 in breast cancer. Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; Apr 16202016, New Orleans, LA: AACR; Cancer Res. 2016; 76(14 Suppl):1835. Abstract no.1835. Spencer SM, Somasagara R, Tripathi K, Clark DW, Kothayer H, Westwell A, Rocconi RP, Palle K. Preclinical evaluation of Rad6 inhibition to overcome platinum resistance in ovarian cancer. AACR Annual Meeting, April 16-20, 2016, New Orleans, LA. Srivastava SK, Singh S, Carter JR, Da Silva ML, Scalici JM, Rocconi RP, Singh AP. MYB: a novel player in pathobiology of ovarian cancer. Gynecol Oncol. 2016; 141:154–5. USA Mitchell Cancer Institute Annual Report

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Srivastava SK, Singh S, Bhardwaj A, Carter JE, Rocconi RP, Scalici J, Singh AP. Multiple functional implications of MYB in ovarian cancer. Cancer Res 2016;76: 1989. Azim S, Srivastava SK, Bhardwaj A, Zubair H, Khan MA, Singh S, Singh AP. Myb-regulated gene networks and signaling pathways in pancreatic cancer. Cancer Res 2016; 76:1519. Tyagi N, Bhardwaj A, Marimuthu S, Srivastava SK, Deshmukh SK, Singh AP, McClellan S, Carter JE, Singh S. p21-activated kinase 4 (pak4) in pancreatic cancer: an emerging therapeutic target. USACOM 8th Annual Research Forum, Dec. 4, 2015, Mobile, AL. Wilk AM, Johnston B, Fouquerel E, Cooper SJ, Sobol RW. Hyperactivation of Poly (ADP-ribose) Polymerase 1 (PARP1) Triggers Global Metabolic Alterations in a Cellular Model of Glioblastoma. (2015) Environmental and Molecular Mutagenesis; v56, S61-S61. Wilk A, Fouquerel E, Schambeau L, Johnston B, Andrews JF, Cooper SJ, Pannell L, Brenner C, Sobol RW. Hyper activation of poly(ADP-ribose) polymerase 1 initiates large-scale metabolic changes in a cellular model of glioblastoma. Cancer Research. 2016; 76(14 Suppl):5280. Woodgate SR, Whittaker C, George J, Schamus-Haynes S, Sobol RW, 96-Well CometChip validation for simultaneous treatment and measurement of DNA damage in a single platform. Cancer Research 2015; 74(19 Suppl):2379. Zou HY, Na P, Hui Z, Dan Y, Ruping C, Haijun C, Guoshuai W, Lili Y, Zhengduo C, Haiying X, Grace Z, Yingchao A, Ritu, Ming, T. Wei, Yongchang Zhou Jia, Shen, Qiang. Abstract 329: Reprogramming glucose metabolism and energy production with a small molecule HJC0152 suppresses breast cancer development and progression to metastasis. Cancer Res 2016; 76(14 Suppl):329. DOI:10.1158/1538-7445. Zhu B, Chen X, Ramirez-Alcantara V, Lee K, Valiyaveettil J, Canzoneri J, Sigler S, Berry K, Lindsey A, Keeton A, Boyd, MR, Piazza GA. A novel Ras inhibitor potently and selectively suppresses lung tumor cell growth by blocking Ras-Raf binding. Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; Apr 16-20, 2016, New Orleans, LA. Abstract 1238. USA Mitchell Cancer Institute Annual Report

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III. PUBLISHED BOOKS Ahmad A, Gadgeel S. Lung Cancer and Personalized Medicine: Current Knowledge and Therapies. Springer 2016. 228 p. Ahmad A, Gadgeel S. Lung Cancer and Personalized Medicine: Novel Therapies and Clinical Management. Springer 2016. 231 p. Ullah MF, Ahmad A. Critical Dietary Factors in Cancer Chemoprevention. Springer 2016. 373 p.

IV. INVITED PRESENTATIONS Ahn EY. Invited Speaker. Regulation of the MLL complex by SON and its isoforms. Workshop on Myeloid development, American Society of Hematology Annual Meeting; Dec 4, 2015; Orlando, FL. Ahn EY. Invited Speaker. Good SON for Healthy Daughters: The role of SON in leukemia and normal development. Cell and Molecular Biology Seminar Series, College of Medicine, University of South Alabama; Apr 6, 2016; Mobile AL. Ahn EY. Invited Speaker. SON-mediated gene expression in leukemia, hematopoiesis and neurodevelopment. UAB Department of Medicine Hematology/Oncology Research Conference; Aug 15, 2016; Birmingham, AL. Daniel CL. Invited speaker. Protecting the skin you’re in. Distinguished Young Women Annual National Finals Life Skills Session; Jun 13, 2016; Mobile, AL. Daniel CL. Invited speaker. Melanoma and skin cancer: Effects on the Gulf Coast. University of South Alabama Mitchell Cancer Institute’s Hope Cup Educational Session; May 12, 2016; Mobile, AL. Daniel CL. Invited speaker. Thriving Post-Cancer: Survivorship. University of South Alabama School of Continuing Education and Special Programs: Generational Resilience Conference; Oct 29, 2015; Mobile, AL. Gassman, NR. Invited speaker. Bisphenol A and UV exposure examining co-exposure effects in skin. As part of the University of Alabamam at Birmingham, Clinical and Translational Science Training Program; Jun 8, 2016; Birmingham, AL. Palle K, Invited Speaker. FANCJ regulates the stability of FANCD2/FANCI proteins and protects them from proteasome and caspase-3 dependent degradation. NIH-DNA repair video conference; Nov 17, 2015. Palle K, Invited Speaker. Regulation of multiple tumor suppressor pathways by Rad18 mediated ubiquiting signaling in response to carcinogens and chemotherapeutics. USA-MCI Data-In-Progress Seminar; Aug 25, 2015; Mobile, AL. Pannell LK. Invited speaker, University of Alabama-Birmingham, Developing pancreatic cancer biomarkers from GLF using microarrays; July 2016; Birmingham, AL.


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Piazza GA. Invited speaker. Seminar topic: Novel anticancer targets and clinical candidates by chemical modification of Sulindac: Beijing Technology and Business University, Nov 16, 2015, Beijing, China Changzhou University, Nov 17, 2015, Changzhou China Zhejiang University, Nov 20, 2015, Hangzhou, China Jinan University, Nov 25, 2015, Guangzhou, China Sun Yat-Sen University, Nov 25, 2015, Guangzhou, China University of Minnesota, Jan 26, 2016 Minneapolis, Minnesota Hormel Research Institute, Jan 27, 2016 Austin, Minnesota MD Anderson Cancer Center, June 2, 2016 Houston, Texas Singh AP. Invited speaker. Understanding and overcoming chemoresistance in pancreatic cancer. Institute of Cancer Research; 2016; Sutton, United Kingdom. Singh AP. Invited speaker. Understanding and overcoming chemoresistance in pancreatic cancer. 10th Global Annual Oncologists Meeting; 2016; Cologne, Germany. Singh AP. Invited speaker. Myb in prostate cancer racial disparity: potential significance as a biomarker and therapeutic target. NCI-sponsored Grantee’s Meeting, 8th AACR Conference on The Science of Cancer Health Disparities in Ethnic Minorities and the Medically Underserved; 2015; Atlanta, GA. Singh AP. Invited speaker. Targeting tumor-stromal cross-talk for pancreatic cancer therapy- Grand Rounds Seminar, Cancer Research Institute, University of North Texas Health Science Center; 2015; Fort Worth, TX. Singh AP. Invited speaker. MYB- a potential molecular determinant of prostate cancer racial disparity. Department of Biology, University of the District of Columbia; 2015; Washington, DC. Singh S. Invited speaker. Behind the Wall of Hope: Understanding Breast Cancer on the Bench. Breast Friends Forever, University of South Alabama; Oct 2015; Mobile, AL. Singh S. Invited speaker. Inflammatory Tumor Micro-Environment and Breast Cancer Racial Disparity: Is There a Link? College of Medicine, University of South Alabama; Apr 2015; Mobile, AL. Sobol RW. Invited speaker. Regulation of Base Excision Repair by Post-Translational Modification. Oregon Institute of Occupational Health Sciences, Oregon Health & Science University; June 1, 2016; Portland OR. Sobol RW. Invited speaker. Cellular mechanisms of repair and response to oxidized nucleotide. Symposium-Frontiers in DNA damage and repair (May 24, 8 am -12 pm) American Society for Photobiology Annual Meeting; May 21-26, 2016; Tampa, FL. Sobol RW. Invited speaker. Next Generation High Capacity DNA Damage Detection Assay for Chemotherapy and Genotoxic Compound Screening AACR Annual Meeting; May 17-19, 2016; New Orleans, LA. Sobol RW. Invited speaker. Base excision repair, ADP-ribosylation and NAD metabolism converge for genome maintenance. Department of Chemistry and Biochemistry, Florida International University; Feb 26, 2016; Miami, FL.


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Sobol RW. Invited speaker. Protein complexes and ubiquitylation regulates base excision repair protein stability. UConn Health Center; Feb 24, 2016; Farmington, CT. Sobol RW. Invited speaker. Base excision repair, ADP-ribosylation and NAD metabolism: A convergence of processes to maintain the genome. University of Alabama, Birmingham, Microbiology Seminar Series; Nov 3, 2015; Birmingham, AL. Sobol RW. Invited speaker. Base excision repair, ADP-ribosylation and NAD metabolism: A convergence of processes to maintain the genome. Oncoveda Cancer Research Center; Oct 21, 2015; Hamilton, NJ. Tan, Ming. Invited Speaker. Reprogram cancer cell glucose metabolism by immunoregulatory protein B7-H3. Cellular & Molecular Biology Journal Club/Research Seminar Series, University of South Alabama; Dec 9, 2015; Mobile, AL. Wilk A. Invited speaker and leader. PARP1 mediated nucleus to mitochondria communication. XF Advanced Cell Metabolism Workshop at MD Anderson Cancer Center; Oct 27-29, 2015; Houston, TX. Wilk A. Invited speaker and leader. Fenofibrate-Induced Metabolic Catastrophe and Cell Death in Glioblastoma. XF Advanced Cell Metabolism Workshop at MD Anderson Cancer Center; Oct 27-29, 2015; Houston, TX.


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V. NATIONAL PROFESSIONAL RECOGNITION Ahmad, Amir Ph.D. Member, Scientific and Organizing Committee, International Conference on Cancer Immunology and Immunotherapy; July 28-30, 2016; Melbourne, Australia. Barnes-Madeira da Silva, Luciana: Committee Member, University of South Alabama College of Medicine Research Forum; Reviewer: PLOS One, Biological Chemistry, Journal of Ovarian Research, Cancer Letters. Gassman, Natalie Ph.D. Full Member, Society of Toxicology; New Investigator Chair for EMGS 2017 Annual Meeting; Editorial Boards: Cancer and Oncology Research, and Integrative Cancer Biology and Oncology Research; Reviewer: DNA Repair, PLoS One, Toxicology Letters. Nirodi, Chaitanya Ph.D. External Doctoral Thesis Examiner, McGill University, Montreal, Canada, Characterization of the cellular and molecular response of Non-Small Cell Lung Adenocarcinoma to stereotactic ablative radiotherapy. Owen, Laurie Ph.D. Member, Mid-South Board American Cancer Society; Member, BioAlabama Board; Member, External Advisory Board University of Texas M.D. Anderson Melanoma SPORE grant. Palle, Kumar Ph.D. served in NIH study section BMCT review panel/rooster, February 11-12, 2016;Reviewed Grants for Fanconi Anemia Research Fund grants, October, 2015;Reviewed Grants for Michigan Regional Comprehensive Metabolomics Resource Core (MRC2) Pilot/Feasibility Grant Program. 2015 funding cycle.;External Faculty Mentoring Committee Member, La Univesidad Metropolitana, San Juan, Puerto Rico (2013 - present);Elected Member of University of South Alabamafaculty senate, (2015- present); Served as Guest Editor – Oxidative Medicine and Cellular LongevitySpecial Issue on “Oxidative Stress in Metabolic Disorders: Pathogenesis, Prevention and Therapeutics” (2015). Serving as an Editorial Board Member of PLOS One (Academic editor) Journal (2014-present). Pannell, Lewis Ph.D. Participated in NIH Study sections during the past twelve months with NCI, NIAID, NIDDK and CSR. Associate member of the NIH Early Detection Research Network for Gastrointestinal Cancers; Associate member of the NIH Early Detection Research Network for Breast and Gynecologic Cancers. Piazza, Gary Ph.D. Study section, Veterans Administration, 2016; Study section, Department of Defense Congressionally Directed Medical Research Programs, 2016; Study section, NCI, R03 grants, 2016; Study section/full member, Chemical and Dietary Prevention Study Section, 2012-2015; Study section/ Chairperson, NCI Omnibus R03 & R21 Study Section, March 2015, Oct 2015; Study section, High Throughput Screening R21 & R01 Study Section, March 2015, Oct 2015; Study section, Department of Defense Congressionally Directed Medical Research Programs, 2015 Member, American Association of Cancer Research (Since 1996) Member, American Society for Pharmacology and Experimental Therapeutics (Since 2015). Prakash, Aishwarya Ph.D. Poster session judge, the Sealy Center for Structural Biology Symposium; Chair, Gordon Research Seminar in DNA repair and Mutagenesis.


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Singh, Seema Ph.D. NIH research proposal (R01-Molecular causes and mechanistic underpinning of breast cancer racial disparity) ranked at 3.0 percentile in scientific merit review. 2016; Mentor and Committee Member: Graduate Committee of Ahmad Al-Ghandhban. Basic Medical Science, University of South Alabama, 2016; Committee Member: Graduate Committee of Mary Patton. Basic Medical Science, University of South Alabama. Major Professor: Dr. Ajay Singh, 2016;Organizing Committee Member: University of South Alabama Research Forum, USA, Mobile, Alabama, 2016; Organizing Committee Member: Oncologists 2016, Cologne, Germany, July 11-13, 2016; Moderator, Day 1 Session: Oncologists 2016, Cologne, Germany, July 11-13, 2016; Mentor and Committee Member: Undergraduate Research Thesis Honors Program, The Pat Capps Covey College of Allied Health, University of South Alabama. Undergraduate Student: Alicia Carrubba, 2016; Mentor and Committee Member: Undergraduate Research Thesis Honors Program, The Pat Capps Covey College of Allied Health, University of South Alabama. Undergraduate Student: Janice Smith, 2016; Panel Member (Scientist Reviewer): DOD- Peer Reviewed Cancer Research Program (PRCRP), 2015; Mentor and Committee Member: Undergraduate Research Thesis Honors Program, The Pat Capps Covey College of Allied Health, University of South Alabama. Undergraduate Student: Janice Smith, 2015; Moderator: Undergraduate Research Program Discussion Panel (University of South Alabama), 2015; Committee Member: Graduate Committee of Joe Otto. Basic Medical Science, University of South Alabama. Major Professor: Dr. Lew Pannel, 2015; Co-organizer: Monthly Pancreatic Cancer Research Focus (PCRF) group meeting at USAMCI, 2015- present.; Committee Member: Planning Committee of Think Pink Tea breast cancer awareness event, USA Mitchell Cancer Institute, Mobile, Alabama, 2016; Team Leader: Learn, Fight and Defeat Team of Making Strides of South Alabama, American Cancer Society Breast Cancer Strides Walk, USA Mitchell Cancer Institute, Mobile, Alabama, 2016; Volunteer: Cancer Survivor Day, USA Mitchell Cancer Institute, Mobile, Alabama, 2016; Organizing Member: ACS Chili Cook off, USA Mitchell Cancer Institute, Mobile, Alabama, 2016;Board Member: Breast Friends Forever, University of South Alabama, Mobile, USA, October, 2015- present; Team Leader: Learn, Fight and Defeat Team of Making Strides of South Alabama, American Cancer Society Breast Cancer Strides Walk, USA Mitchell Cancer Institute, Mobile, Alabama, 2015;Volunteer: Cancer Survivor Day, USA Mitchell Cancer Institute, Mobile, Alabama, 2015; Committee Member: Planning Committee of Think Pink Tea breast cancer awareness event, USA Mitchell Cancer Institute, Mobile, Alabama, 2015; Run way Model: “Think Pink Tea” Breast Cancer Awareness Event, USA Mitchell Cancer Institute, Mobile, Alabama, 2015; Committee Member & Head Chef: ACS Chili Cook off, USA Mitchell Cancer Institute, Mobile, Alabama, 2015. Sobol, Robert W. Ph.D.; 2013-present Study Section Member, Israel Cancer Research Fund (ICRF); 2013-2016 Councilor Environmental Mutagenesis and Genomics Society (EMGS); 2013-2016 Awards & Honors Committee member, Environmental Mutagenesis and Genomics Society (EMGS); 20132016 Nominating Committee member; Environmental Mutagenesis and Genomics Society (EMGS); 2015-Present Chair, DNA Mechanisms of Cancer Study Section American Cancer Society (ACS); 2016 Vice-President Elect and 2017 Program Chair Environmental Mutagenesis and Genomics Society (EMGS); 2016-2019 Committee member American Association for Cancer Research (AACR)Science Policy and Government Affairs Committee (SPGAC);2016-2020 Cancer Etiology (CE) Study Section, standing member, National Institutes of Health (NIH), (July 2016-June 2020);2017Co-organizer 6th EU-US Conference on Repair of Endogenous DNA Damage University of Udine, Italy (September 2428, 2017); 2017 President Elect and Program Chair, 2017 Annual Meeting, Environmental Mutagenesis and Genomics Society (EMGS), Raleigh, NC (September 8-13, 2017); 2015, Ad hoc reviewer, NIH Study Section; Cancer Health Disparities/Diversity in Basic Cancer Research, CDH (April 2015); 2015 Ad hoc reviewer, NIH Study Section; NIH Common Fund’s 4D Nucleome Program; Nucleomics Tools (U01) (RFARM-14-007) (June 2015); 2015;Ad hoc reviewer, NIH Study Section; Special emphasis panel, Scientific Review Group 2016/01 ZCA1 SRB-L (J1); (October 2015); 2015 Ad hoc reviewer, DoD Study Section; 2015 Lung Cancer Research Program, Cell and Molecular Biology, CMB; (November 2015); 2016 Ad hoc reviewer, NIEHS (NIH), P42 Superfund Research Program (August 2016); 2017/01 ZES1 LKB-K (S) 1; Superfund Hazardous Substance Research and Training Program; 2016 Ad hoc reviewer, 2016/10 ZES1 LWJ-D (TS) 1; Review of Time Sensitive R21s (Teleconference). USA Mitchell Cancer Institute Annual Report

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Tan, Ming Ph.D. Member, Study Sections: NIH Meeting 2016/01 ZRG1-OTC-X-55, R01 “Metabolic Reprogramming in Immunotherapy” 2016, DoD Breast Cancer Research Program CET-6 2016; Scientist Reviewer, The South African Medical Research Council (MRC) 2016; Editorial Boards: Scientific Reports (Nature Publishing Group), PLoS ONE, International Journal of Cell Biology, Chemotherapy (Open Access), Journal of Cancer Biology & Treatment, Journal of Cell Biology & cell metabolism; Reviewer: Cancer Research, Nature Communications, Science Translational Medicine, Oncotarget, Oncogene; Advisory Board Member: Cancer Carcinogenesis and Invasiveness Key Lab of the Chinese Ministry of Education; Guest Professor, University of Central South China. Wilk, Anna Ph.D. Anna Wilk, Ph.D. Reviewer: PLos One, Cancer Letters, Scientific Reports.


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VI. BRIEF SUMMARY OF ACTIVITIES AND PROGRESS Ahmad, Amir Ph.D. I joined as a Research Assistant Professor in the Health Disparities in Cancer Research Program in Feb 2016 and am working on understanding the epigenetic basis of lung cancer racial disparity. My other research projects are focused on understanding the mechanisms of drug resistance (erlotinib resistance in lung cancer and tamoxifen / herceptin resistance in breast cancer) and brain-metastasis of primary lung and breast cancers. Ahn, Erin Ph.D. During the current fiscal year, two peer-reviewed research papers were published in highly respected journals in the field of the molecular cancer biology and genetics. Four abstracts were published for the internationally recognized conferences, such as American Association for Cancer Research and American Society of Hematology Annual meetings. Several opportunities to present as an invited speaker has further opened close collaborations with USA College of Medicine and UAB as well as international research groups. Several projects are ongoing and planned for future publications and presentations in international meetings. Collaborations for leukemia and hematology research will be set with research groups in UAB during next fiscal year. Barnes-Madeira da Silva, Luciana PDE10A as novel molecular target for ovarian cancer chemoprevention and therapy. My main focus in the period of Oct/15 to Sep/16 has been on developing the project related to NIH R01 Supplemental Award 3R01CA155638-04S1 under Dr. Gary Piazza’s mentorship. I have been developing the ground work related to the characterization of PDE10A as a biomarker in human ovarian cancer, characterization of PDE10A oncogenic function in human ovarian cancer cell lines in vitro by using genetic approaches (siRNA/shRNA/CRISPR knockout) as well as small molecules that inhibit PDE10A, such as a known PDE10 inhibitor from Pfizer (Pf-2545920) and Dr. Piazza’s novel sulindac derivatives, including MCI-030. I expect to submit two manuscripts with results of this project in the next fiscal year. I am also submitting a proposal to the Exploratory Grant Award to Promote Workforce Diversity in Basic Cancer Research (R21) (PAR-15-053), due November 30, 2016. Novel sulindac derivatives that inhibit PDE10A as a chemoprevention agents in the spontaneous laying hen ovarian cancer model. This is a project headed by Dr. Jennifer Scalici in collaboration with Dr. Gary Piazza and Dr. Wallace Berry (Poultry Sciences at Auburn University) and Dr. Dale Buck Hales (Southern Illinois University School of Medicine). I have been supervising hen PK studies performed with sulindac and MCI-030. Dr. Scalici was invited and just submitted a full application for OCRP DoD Pilot Award to conduct a MTD and efficacy study comparing sulindac and MCI-030; my role in the project will be to perform the molecular characterization of the effects of these compounds. Novel active Ras-selective compounds for ovarian cancer treatment. I have been working in collaboration with Dr. Gary Piazza to test his novel “Ras compounds” in ovarian cancer intraperitoneal xenograft models, where we have already seen efficacy for MCI-059. In the next fiscal year I will be expanding in vivo experiments to confirm our results and also working on in vitro characterization of Ras activity in various ovarian cancer cell lines and signaling pathways inhibited by these compounds. I expect to submit an abstract to the 2017 AACR Annual Meeting in December, 2017, followed by a publication. Molecular basis for ovarian cancer health disparities. This is a project that Dr. Rodney Rocconi initiated with Hudson Alpha Institute and I have been supervising the selection of patient samples along with the Department of Pathology at USA. We recently submitted almost 100 clinical paraffin-embedded USA Mitchell Cancer Institute Annual Report

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ovarian tumor tissue cores for exome RNA sequencing and racial genetic admixture determination by MEGA DNA analysis at Hudson Alpha, half of which from African American patients and the other half from Caucasian patients. We expect to obtain sequencing data in the next 3 months, which will be an extremely valuable resource for us to evaluate potential molecular markers associated to race in our local patient population. Our hope is that this pilot project will provide preliminary data for an R01 proposal in ovarian cancer health disparities. Furthermore, this gene expression profile data will also provide a valuable platform for various collaborative projects that we have ongoing at MCI. Development of PDxChip ovarian cancer model. This is a project in collaboration with Dr. Robert Sobol that has been awarded the 2015 Alabama Institute of Medicine Stem Cell Research Grants Program. In the next fiscal year, I will be working with Dr. Sobol’s group to start developing ovarian cancer organoids using the PDxChip platform, in collaboration with Trevigen, Washington University in St. Louis and UAB. Our ultimate goal in this project is to compare the molecular profile and drug sensitivity of these organoids with primary tumors and PDx animal models of ovarian cancer to evaluate whether organoids could be developed as a cheaper/faster alternative to predict patient therapeutic outcomes. Role of cancer stem cells in chemotherapy resistance in ovarian cancer. In collaboration with Verastem, we showed that chemotherapy increases expression of a panel of cancer stem cell markers. This work has been presented by Dr. Jennifer Scalici as oral presentation at the 2016 SGO Meeting and we have a manuscript that will be submitted for publication within the next week. Investigating the role of the checkpoint blockade protein B7-H3 in ovarian cancer. I am Research Mentor for the undergraduate student Holly Taylor in the BMD 499 USA Biomedical Sciences Honors Program. Her Honors thesis is focused on evaluating the role of B7-H3 in ovarian cancer. So far, we have generated an ovarian cancer B7-H3 knockout cell line (OV-90 B7-H3ko) using CRISPR/Cas9 genome editing and we are in the process of characterizing this cell line in vitro, having completed basic screening assays where we verified decreased colony formation ability upon knockout of B7-H3, an increased sensitivity to carboplatin, as well as decreased STAT3 signaling pathway and metabolic componenets such as LDHA and PDK1. In the next fiscal year we are planning to expand our work with further in vitro characterization to include functional assays that measure cancer cell migration and invasion properties, metabolic profile, and to perform an in vivo experiment using the intraperitoneal xenograft model of ovarian cancer in nude mice. Holly Taylor is expected to complete this work by Spring/2017 when she will defend her Honors Thesis. In addition to her thesis work, I am also engaged in characterizing B7-H3 in clinical specimens of ovarian cancer patients to understand the clinical relevance of B7-H3. I will be I expect to submit our results for publication in the next fiscal year and will be seeking extramural funding for this project with Dr. Ming Tan’s collaboration. Bhardwaj, Arun Ph.D. During the current fiscal year, I made significant progress in multiple research projects to understand the molecular basis of cancer development and/or progression, identify putative targets for therapy, and develop novel therapeutic approaches against various cancer types in collaboration with Research and Clinical team members. Specifically, my pre-clinical studies revealed that co-inhibition of CXCL12/ CXCR4 and hedgehog pathway enhances chemo-therapeutic response in orthotopic mice model of pancreatic cancer. In addition, my investigations identified a novel role of MYB, an oncogenic transcription factor, in pancreatic tumor growth, metastasis, and desmoplasia. Daniel, Casey Ph.D. Elected Vice-Chair of Alabama Comprehensive Cancer Control Coalition, April 2016. Appointed Associate Scientist at University of Alabama at Birmingham (UAB) Comprehensive Cancer Center, March 2016. Appointed Adjunct Assistant Professor, Department of Health Behavior, School of Public Health at University of Alabama at Birmingham (UAB), February 2016.


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Fang, Qingming Ph.D. Project 1: TRIP12 governs DNA polymerase ß involvement in replication-associated base excision repair. The study shows that HSP90 regulates DNA repair via the interaction of the base excision repair proteins XRCC1 and DNA polymerase ß in a DNA damage and cell cycle context dependent manner. The data show that the interaction of Polß/XRCC1 is not required for the cellular response to DNA base damage while disruption of the interaction promotes ubiquitylation and proteolysis of Polß but not XRCC1. Reported Mule and CHIP are not involved and K206 and K244 residues located in c-terminal domain is targeted by ubiquitylation. It is unknown which E3 ligase(s) target Polß (Fang Q, Inanc B, et al. Nature Communications, 2014, 5: 5513). A novel strategy was designed to screen novel interactors of Polß and figure our which E3 ligases target Polß. With immunoprecipitation-differential mass spectrometry (IP-dMS) method, we identified that TRIP12 interacts with Polß independent of XRCC1. We discovered that TRIP12 only interacts with the C-domain of Polß and the HECT domain of TRIP12 only interacts with Polß free of XRCC1. The association of XRCC1 with Polß also greatly affects the interaction of TRIP12/Polß. Further we found that TRIP12 targets Polß for ubiquitylation and degradation in response to DNA damage and the deficiency of TRIP12 results in the accumulation of Polß in chromatin after DNA damage. These data show that TRIP12 governs Polß chromatin retention upon DNA damage and regulates localization and Polß involvement in late replication associated repair. This finding is very important and novel. We plan to submit this finding to Cell for publication this year. Project 2: Polß cancer mutant T304I affects the stability of Polß and the cellular response to chemotherapy and radiotherapy. The data show: 1, T304I mutation efficiently disrupts the Polß/ XRCC1 interaction and promotes robust ubiquitylation of Polß and rapid degradation of Polß; 2, T304I mutation results in both ubiqtuin-dependent and ubqiutin-independent proteasome degradation; 3, Polß deficiency sensitizes HCT116 cells to MNNG and MNNG plus PARP inhibitor. Project 3: The crosstalk between base excision repair (BER) and non-homologous end joining (NHEJ) repair via the interaction of XRCC1/Ku70-Ku80. With differential mass spectrometry (dMS), we found that XRCC1 interacts with Ku70-Ku80. Further results show that XRCC1 interacts with Ku70-Ku80 in both LN428 and T98G cells and this interaction cannot be removed by treatment of EtBr and MN nuclease during IP process, suggesting this interaction is not due to the contamination of DNA. Many experiments are ongoing. Gassman, Natalie Ph.D. Co-investigator on awarded Defense University Research Instrument Program (DURIP) grant from the Office of Naval Research, which will purchase a new confocal microscope for USAMCI. Transitioned a K99/R00 Pathway to Independence Award from the National Institute of Environmental Health Sciences to USAMCI, which examines the influence of the endocrine disruptor bisphenol A on the cellular microenvironment and DNA damage and repair. Work from this grant has resulted in a publication this year, poster presentations at two national meetings, and a travel award to the 2016 Environmental Mutagenesis and Genomics Society annual meeting for a postdoctoral researcher in my laboratory. Developed an internal collaboration with Dr. Marcus Tan and Casey Daniel, PhD, MPH, which uses translational research to examine the tanning behaviors of adolescent young adults and the cellular consequences of these behaviors. The research focuses on indoor and sunless tanning, which have grown in popularity with high school and college students. Our Cutaneous Oncology Research Collaborative (CORC) has surveyed the USA and Springhill College student bodies to assess tanning behaviors and motivations, and we are currently preparing several manuscripts for publication. Additionally, we have authored several grant applications to fund this research and acted as preceptors to UAB Cancer Research Experience for Students (CaRES) interns. I acted as a preceptor for Harrison School of Pharmacy at USA student, who examined the cytotoxicity of sunless


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tanning products over the summer as part of the CaRES program. We also developed a relationship with the Distinguished Young Women program, based here in Mobile, in order to survey adolescent young women that may face peer pressure to tan and conducted an informational seminar for the 50 state representatives that were competing for the Distinguished Young Women scholarship in June. Additionally, I have completed the UAB Clinical and Translational Science Training Program, which provides education and training opportunities in clinical and translational research over a six-month period; participated in the USA Faculty Senate’s mentorship program as a mentee; and mentored a USA undergraduate and Mobile area high school student in the laboratory. I have also been involved in the development and planning of the 2017 Environmental Mutagenesis and Genomics Society annual meeting, as the New Investigator Chair, and I have received a travel subsidy to act as a judge for the 2016 Annual Biomedical Research Conference for Minority Students. Li, Jianfeng Ph.D. Glioblastoma (GBM) is one of the most lethal primary malignant brain tumors, with less than a 15-month average survival. Glioma stem cells (GSCs), with the capability of extensive self-renewal and multi-lineage differentiation, are thought to initiate and promote glioma development as well as promote the therapeutic resistance and recurrence of GBM. We are focusing on the genes aberrantly expressed in GSCs to discover the new targets for GBM therapy. We unveiled that ARTD4 (PARP4) was more than 10 fold upregulated in mesenchymal (MES) subtype GSCs exclusively by a microarray analysis. We confirmed the ARTD4 expression in protein level in MES GSCs, finished targeting depletion of the expression of ARTD4. We investigated the tumor cells growth in vitro and tumor growth in vivo in Immunocompromised mouse model. We found the depletion of ARTD4 inhibited GSC cell proliferation and tumor growth via activating apoptosis pathway. We submitted a R21 grant in Aug. 2016 for further discovery of the substrates and protein-protein interaction of ARTD4 for the further understand of the biological function of ARTD4, which is majorly unknown. Pannell, Lewis Ph.D. The primary focus of the research group is on the early detection of both gastrointestinal and gynecological cancers, with special focus on pancreatic ductal adenocarcinoma and ovarian cancers. The ovarian work is covered under an NIH grant that has involved the collection of over 400 samples and the data collection form these is the current main activity which will be followed by data analysis. The pancreatic cancer research has looked at peptides, proteins, glycans and the immune system response for the source of biomarkers. The latter data is being collected under contract at Arizona State University in their microarray core. There were extremely promising results from the smaller sample set of 16 controls and 10 pancreatic cancer that have led to the sending out of 225 samples for data collection. As with all of the data and measurements being made in the facility, there is a major effort in the development of computational methods for data analysis and this is currently being optimized for the large data set about to be received. This new data set, based on the extremely promising results from the pancreatic studies, includes a set of ovarian cancer samples and controls for preliminary testing using samples obtained under the ovarian grant. The group consists of the PI, a senior lab manager, a South Alabama postdoctoral student and three graduate students. Both areas of work are in collaboration with small businesses looking at commercial development.


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Prakash, Aishwarya Ph.D. I joined the Mitchell Cancer Institute as an Assistant Professor as part of the Molecular and Metabolic Oncology program on March 1st, 2016. I obtained a joint appointment with the Department of Pharmacology at the University of South Alabama (USA) and identified a faculty mentor, Dr. Richard Honkanen in the Department of Biochemistry at USA. Attended the Gulf Coast ADVANCE Faculty Retreat – Feb 26th, 2016. I successfully wrote an application to transfer a K99/R00 NIH Pathway to Independence award from the mentored (K99) phase to the independent (R00) phase. This was completed on April 1st, 2016, which marked the start of the grant. I recruited two post-doctoral research fellows to participate in research involving mitochondrial DNA repair and cancer, who began their research in my laboratory in May 2016. I spearheaded the initiative to develop a training environment for post-doctoral research fellows and trainees by organizing quarterly Lunch & Learn seminars on topics such as finding your niche, jobs for PhDs, academia vs. industry etc. The first of this series was held on June 1st, 2016 and was presented by Dr. Kimberley Littlefield, Assistant Vice President for Research Development and Learning, USA, Office of Research and Economic Development. I participated in the College of Medicine Summer Medical Student Research Program, University of South Alabama, June 1st- July 31st, 2016. Joshua Kay, a second year medical student performed a summer research project in the lab where he established a new cloning technique called “Gibson Assembly”. He spent his time learning techniques such as protein expression, protein purification, and cloning methods. I am involved with mentoring Monica Sai Pascala, a freshman undergraduate honors college student at USA, who will be performing her honors thesis in the lab. In April 2016, I applied for a Gulf Coast ADVANCE fellowship. I am also listed as co-pI (with 5% effort) on Dr. Chaitan Nirodi’s (MCI) R21, NIH grant that was submitted in July and as a collaborator on Dr. Robert Sobol’s (MCI) R21, and R01 grants that were submitted in July and August 2016, respectively. Singh, Ajay Ph.D. I have been conducting researches on the molecular mechanisms of pancreatic cancer progression, metastasis and chemoresistance, and exploring the biological basis of racial disparity in prostate cancer. In addition, I have also been collaborating with other scientists within and outside MCI. Our collaborations have resulted in several joint publications and grant funding including a five year R01 on breast cancer racial disparity (PI: Seema Singh). Besides, I have been given the responsibility to build “Health Disparities in Cancer Research” Program at USAMCI. As part of this process, we have recruited a Research Assistant Professor from Wayne State University, Michigan. We have also interviewed a candidate for a tenure-track/Tenured faculty position to further expand the program. We also submitted two SBIR proposals in collaboration with “Tatva Biosciences” to develop novel models for advancing cancer health disparity research. We received favorable reviews on both proposals and one is expected to receive funding (currently in negotiation phase). I have also been organizing/coorganizing “pancreatic cancer research facus” and “NanoBio Research Interest” group meetings on a monthly basis to promote discussions and collaborations among researchers and physician scientists. I also served on the Organizing committee of 2015 NanoBio Summit that was held at University of Alabama at Birmingham. I am also serving on the Organizing Committee of 2016 NanoBio Summit that will be held at Auburn University in October and planning to bring the summit to Mobile (University of South Alabama) next year.


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Singh, Seema Ph.D. My research interest is in understanding the molecular causes and mechanistic underpinning of breast cancer racial disparity and also understanding the mechanisms of pancreatic cancer progression, metastasis and chemoresistance. In addition, I also have been studying the Chemoprotective role of silver nanoparticles in UV-radiation induced skin carcinogenesis. I have also been collaborating with other scientists within and outside of MCI. Our collaborations have resulted in several joint publications and grant funding including a five year R01 on breast cancer racial disparity. We also submitted two SBIR proposals in collaboration with “Tatva Biosciences” to develop novel models for advancing cancer health disparity research. We received favorable reviews on both proposals and one is expected to receive funding (currently in negotiation phase). I have also been organizing/co-organizing “pancreatic cancer research focus” and “NanoBio Research Interest” group meetings on a monthly basis to promote discussions and collaborations among researchers and physician scientists. Sobol, Robert W. Ph.D. Research activity during the current fiscal year: Research in my lab has moved well in FY2015/2016. The lab is now full (Fang, Li, Wilk, Sykora and Zamani) and we have recovered from the move in 2014 to be fully active. As director of the MCI Molecular & Metabolic Oncology Program, my current major tasks involve recruitment. In 2015/2016, the following investigators have been recruited: Starting July 2015, Natalie R. Gassman, Assistant Professor of Oncologic Sciences; Starting March 2016, Aishwarya Prakash, Ph.D., Assistant Professor of Oncologic Sciences; Starting November 2016, Marie Migaud, PhD, Professor of Oncologic Sciences. Srivastava, Sanjeev Ph.D. I am engaged in a large and impressive research program that encompasses the areas of prostate, pancreatic, breast and ovarian cancer to identify novel deregulated genes and dissect their underlying regulatory pathways and functional significance. Moreover, in our NIH/NCI funded U01 grant I am working as a team leader. The major focus of this funded project is to investigate the role and underlying molecular mechanisms of MYB in prevalent prostate cancer racial disparity. In addition to these, I am also a coordinator of Pancreatic Cancer Research Focus (PCRF) group meeting at University of South Alabama Mitchell Cancer Institute (USAMCI). Goal of this meeting is to foster collaborations and interactions among researchers and clinician scientists at USAMCI and University of South Alabama. Sykora, Peter Ph.D. New to MCI in 2015. As manager of the technology development facility I worked on a novel high through-put method of measuring DNA damage and repair in a variety of cells and also pertinently, in patient samples. The new protocol has already been adopted by other laboratories at MCI and externally. This includes collaboration with a marine science group investigating marine toxins and potential human consequences. We are expecting multiple peer-reviewed publications from this research in the coming months. Tan, Ming Ph.D. During the 2015-2016 fiscal year, my group published 15 peer reviewed journal articles, 8 published abstracts. I gave 1 invited presentation. As a scientist reviewer, I participated in 2 study section meetings, and served as a mail reviewer for another funding agency. I serve on editorial boards of many journals, including well-known journals such as Scientific Reports (NPG), PLoS ONE, and International Journal of Cell Biology et al. I reviewed manuscripts for journals such as Cancer Research, Oncogene, Nature Communications, Science Translational Medicine, et al. I also served on the advisory board of a cancer institute and served as a guest professor for a university in China.


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Wilk, Anna Ph.D. As I transitioned to my first junior faculty position I expanded my research interest by combining mechanisms of DNA damage, DNA repair and metabolism. Specifically, in collaboration with Dr. Marie Migaud I developed a project where we looked at the effects of extracellular supplementation of nicotinamide metabolites on cellular NAD+ level. I identified a unique mechanism of posttranslational modification of NMRK1 enzyme in response to NAD+ depletion. Currently, I am collecting final data and preparing a manuscript to be published. A second project in which I am involved focuses on the difference in response to genotoxic treatment between human embryonic stem cells, induced pluripontent stem cells and their differentiated to cardiomyocytes counterparts. This project is being performed in collaboration with Stacy Gelhaus Wendell from Biomedical Mass Spectrometry Center in Pittsburg as well as Steve MC McClellan and Jaroslav Slamecka from MCI. The project was submitted as a R21 grant application by Dr. Sobol as a principal investigator. We are in the process of collecting more data for publication and potential resubmission of the grant. The last project which I contribute to is focused on Polymerase β (Pol β) expression in patients with head and neck cancers. I used xenograph model to developed human tumors with differential expression of Pol β which will be utilized as controls for patient samples. This project was submitted as a grant application by Dr. Sobol as a principal investigator. We are working towards collecting more data for future publications related to this subject.


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Summary of Scholarly Activities Gynecologic Oncology


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“We hope to truly offer a bench-to-bedside approach where our discoveries in the lab can continue to impact our patients and women who are afflicted with gynecological cancers with the hope of eliminating these diseases in the years to come.”

– Rodney P. Rocconi, M.D. Chief of Gynecologic Oncology Services Associate Director of Clinical Research

During 2016, our services expanded as we added two nurse practitioners to the Gynecologic Oncology team, Mary Lucy Mattei and Dr. Leigh Minchew. The division is also active in clinical trials, accounting for nearly 74 percent of all MCI clinical trials enrollment. We are proud to have the only cancer site-specific basic and translational research lab for gynecologic malignancies. In the past 24 months, the lab has received seven large grants totaling nearly $2 million in funding.


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I. PUBLISHED JOURNAL ARTICLES, BOOK CHAPTERS AND PATENTS L Amable, E Gavin, K Kudo, E Meng, RP Rocconi, LA Shevde, E Reed. GLI1 upregulates C-JUN through a specific 130 kDa isoform. International Journal of Oncology 2014, 44(3): 655-61. doi: 10.3892/ ijo.2013.2222. PMID 24366538. W Stroud, JM Whitworth, M Miklic, KE Schneider, MA Finan, E Reed, L Bazzett-Matabele, JM Straughn, RP Rocconi. Validation of a venous thromboembolism risk assessment model in gynecologic oncology. Gynecologic Oncology 2014; 134(1):160-63. Doi: 10.1016/j.ygyno.2014.04.051 PMID 24796634. E Meng, A Mitra, K Tripathy, MA Finan, J Scalici, S McClellan, E Reed, LA Shevde, K Palle, RP Rocconi. ALDH1A1 maintains ovarian cancer stem cell-like properties by altered regulation of cell cycle checkpoint and DNA repair network signaling. PLOS One 2014; Sep 12;9(9):e107142. doi: 10.1371 PMID: 25216266. K Tripathi, C Mani, R Barnett, S Nalluri, L Bachaboina, RP Rocconi, M Athar, Laurie Owen, K Palle. Gli1 protein regulates S-phase checkpoint in tumor cells via Bid protein, and its inhibition sensitizes to DNA topoisomerase 1 inhibitors. The Journal of Biological Chemistry 2014; 7:289(45): 31513-25. Doi: 10.1074/ jbc.M114.606483. PMID: 25253693. J Scalici, B Laughlin, MA Finan, B Wang, RP Rocconi. The trend towards minimally invasive surgery for endometrial cancer: An ASC-NSQIP evaluation of surgical outcomes. Gynecologic Oncology 2014; doi: 10.1016/j.ygyno.2014.11.014. PMID: 25462206. H Dalton, J Fiorica, BJ Monk, I Benjamin, RP Rocconi, F Recio, J Lovecchio, M Burrell, R Brown, CK McClure. In Vitro Chemoresponse in metachronous pairs of gynecologic cancers. Anticancer Research 2014; 32(12): 7191-6. PMID: 25503148. K Tripathi, UK Hussein, R Anupalli, R Barnett, L Bachaboina, J Scalici, RP Rocconi, LB Owen, G Piazza, K Palle. Allyl isothiocynate induces replication-associated DNA damage response in NSCLC cells and sensitizes to ionizing radiation. OncoTarget 2015; 2015 Mar 10;6(7):5237-52. PMID: 25742788. GE Konecny, N Finkler, AA Garcia, D Lorusso, P Lee, RP Rocconi, PC Fong, M Squires, K Mishra, A Upalawanna, Y Wang, R Kristeleit. Second-line dovitinib (TKI258) in patients with FGFR2-mutated or FGFR2-non-mutated advanced or metastatic endometrial cancer: a non-randomised, openlabel, two-group, two-stage, phase 2 study. Lancet Oncology DOI: http://dx.doi.org/10.1016/S14702045(15)70159-2 PMID 25981814. S McClellan, J Slamecka, P Howze, L Thompson, MA Finan, RP Rocconi, L Owen. mRNA detection in living cells: A next generation cancer stem cell identification technique. Methods. 2015 Jul 1;82:47-54. doi: 10.1016/j.ymeth.2015.04.022. Epub 2015 Apr 25. PMID: 25920950 J Scalici, MA Finan, J Black, MD Harmon, W Nicolson, HA Lankes, WE Brady, RP Rocconi. Minority participation in Gynecologic Oncology Group (GOG) studies. Gynecol Oncol. 2015 Aug;138(2):441-4. doi: 10.1016/j.ygyno.2015.05.014. Epub 2015 May 23. PMID: 26013697 RP Rocconi, H Lankes, W Brady, KM Darcy, PJ Goodfellow, NC Ramirez, RD Alvarez, W Creasman, JR Fernandez. The role of racial genetic admixture with endometrial cancer outcomes: An NRG Oncology/ Gynecologic Oncology Group study. Gynecologic Oncology 2016 Feb;140(2):264-9. doi: 10.1016/j. ygyno.2015.11.018. Epub 2015 Nov 18. PMID: 26603970 USA Mitchell Cancer Institute Annual Report

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RR Somasagara, K Tripathi, SM Spencer, DW Clark, R Barnett, L Bachaboina, J Scalici, RP Rocconi, GA Piazza, K Palle. Rad6 upregulation promotes stem cell-like characteristics and platinum resistance in ovarian cancer. Biophysical and Biophysical Research Communications 2016 Jan 15;469(3):449-55. doi: 10.1016/j.bbrc.2015.11.134. Epub 2015 Dec 8. PMID: 26679603 CJ Pannucci, RP Rocconi. The limited utility of currently available venous thromboembolism risk assessment tools in gynecologic oncology patients. Am J Obstet Gynecol 2016 July doi doi: 10.1016/j. ajog.2016.06.052. PMID: 27390115 J Scalici, J Black, C Brown, B Wang, MA Finan, RP Rocconi. Surgical racial disparity in the treatment of endometrial cancer patients undergoing hysterectomy: An ACS-NSQIP evaluation. (Submitted to Cancer) A Ahmad, S Azim, H Zubair, M Khan, S Singh, J Carter, RP Rocconi, A Singh. Epigenetic Basis of Racial Disparity in Cancer: Looking Beyond Genetic Differences. (Submitted to BBA Reviews on Cancer) SK Deshmukh, S Azim, A Ahmad, H Zubair, N Tyagi, S Srivastava, A Bhardwaj, S Singh, RP Rocconi, A Singh. Fueling Cancer Health Disparities Research: Molecular basis, Resources and Challenges for Advanced Research. (Submitted to Cancer Letters) SK Deshmukh, S Azim, A Ahmad, H Zubair, N Tyagi, S Srivastava, A Bhardwaj, S Singh, RP Rocconi, A Singh. Biological Basis of Cancer Health Disparities: Resources and Challenges for Basic Research. (Submitted to American Journal of Cancer Research) JG Ross, KV Braswell, JM Scalici, L Madeira da Silva, F Mujica, S Stutsman, W Nicolson, MD Harmon, S Boudreau, B Wang, MA Finan, and RP Rocconi. Unraveling the etiology of ovarian cancer racial disparity in the Deep South: Is it nature or nurture? (Submitted to Gynecologic Oncology)


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Patents 2010 �� Novel Molecular Assays and Uses Thereof Co-Inventor - U.S. Patent Application # 12/646,592 2011..............................................................Method and Composition for the Treatment of Ovarian Cancer Co-Inventor - U.S. Patent Application # 61/537,521 2011....................................................Iron Modified Peptides as Biomarkers for Gynecologic Malignancies Co-Inventor - U.S. Patent Application # 61/520,108 2012........................................... Methods and Compositions for Detecting Endometrial or Ovarian Cancer Co-Inventor - U.S. Patent Application # 61/614,347 2012........................................... Methods and Compositions for Detecting Endometrial or Ovarian Cancer Co-Inventor - U.S. Patent Application # 61/614,393 2012........................................... Methods and Compositions for Detecting Endometrial or Ovarian Cancer Co-Inventor - U.S. Patent Application # 13/487,026

II. ABSTRACTS (PRESENTED AT NATIONAL CONFERENCES) R Barnett, K Tripathi, L Bachaboina, U Hussien, J Scalici, RP Rocconi, K Palle. Dietary isothiocyanates inhibit cancer cell growth by inducing replication stress mediated DNA damage response. Featured poster at Society of Gynecologic Oncology Annual Meeting on Women’s Cancer. Chicago, IL, March 2015. RP Rocconi, J Scalici, E Reed, TL Felix, MA Finan. A phase I study of hypomethylating agent azacitadine (Vidaza) in combination with the nanoparticle albumin-bound paclitaxel (Abraxane): Efficacy results of heavily pre-treated gynecologic oncology patients. Featured poster at Society of Gynecologic Oncology Annual Meeting on Women’s Cancer. Chicago, IL, March 2015. LM da Silva, K Lee, G Piazza, L Bachaboina, RP Rocconi, JM Scalici. Investigating the role of phosphodiesterase 10A as a novel target in ovarian cancer. Poster presentation at Society of Gynecologic Oncology Annual Meeting on Women’s Cancer. Chicago, IL, March 2015. RP Rocconi, JM Scalici, D Billheimer, B Mannakee, L Schambeau, L Pannell, MA Finan. Early detection of ovarian cancer via a self-sampling screening test of vaginal secretions: Feasibility and patient acceptance. Poster presentation at Society of Gynecologic Oncology Annual Meeting on Women’s Cancer. Chicago, IL, March 2015. S Spencer, K Tripathi, E Meng, J Scalici, RP Rocconi, K Palle. A novel combination of Hedgehog inhibitors with carboplatin exhibits synergy in ovarian cancer treatment by altered regulation of DNA repair networks. Poster presentation at AACR Annual Meeting. Philadelphia, PA, April 2015.


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K Bevis, G Cantuaria, RP Rocconi, MA Finan, J Scalici, GB Rocque, EA Kvale, A Acemgil, RA Taylor, W Demark-Wahnefried, K Kenzik, K Meneses, M Martin, N Fouad, EE Partridge, M Pisu. Understanding causes of distress in women with gynecologic cancer. Poster presentation at the American Society of Clinical Oncology Annual Meeting. Chicago, IL, May 2015. L Schambeau, T Conrads, MA Finan, RP Rocconi, L Owen, M Chambers, L Pannell. Discovery of proteomic biomarkers of ovarian cancer with multiple data analysis approaches. Poster presentation American Society for Mass Spectrometry Annual Meeting. St. Louis, MO, June 2015. K Bevis, G Cantuaria, RP Rocconi, MA Finan, J Scalici, GB Rocque, EA Kvale, A Acemgil, RA Taylor, W Demark-Wahnefried, K Kenzik, K Meneses, M Martin, N Fouad, EE Partridge, M Pisu. Understanding causes of distress in women with gynecologic cancer. (Submitted to the American Society of Clinical Oncology Palliative Care in Oncology Symposium. Boston, MA, October 2015.) SM Spencer, K Tripathi, RP Rocconi and K Palle. Rad6 inhibition attenuates activation of multiple DNA repair networks and sensitizes ovarian cancer cells to platinum drugs. Environmental Mutagenesis and Genomics Society 46th Annual Meeting, September 26-30, 2015; New Orleans, LA (Poster). SM Spencer, RR Somasagara, RM Barnett, K Tripathi, RP Rocconi, and K Palle. In vitro evaluation of Rad6 inhibition to overcome platinum resistance in ovarian cancer. Molecular Therapeutics of Cancer Research Conference, July 12-16, 2015; Medford, MA (Poster). SM Spencer, K Tripathi, E Meng, JM Scalici, RP Rocconi, and K Palle. A novel combination of Hedgehog inhibitors with carboplatin exhibits synergy in ovarian cancer treatment by altered regulation of DNA repair networks. AACR Annual Meeting, April 18-22, 2015; Philadelphia, PA (Poster).


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SM Spencer, K Tripathi, C Mani, D Clark, RP Rocconi, R Barnett, and K Palle. Inhibition of Rad6 sensitizes ovarian cancer cells to chemotherapy. USA College of Medicine Research Forum, October 31, 2014., Mobile, AL (Poster). L Madeira da Silva, E Gavin, K Lee, I Aragon, V Ramirez-Alcantara, J Scalici, RP Rocconi, GA Piazza. Targeting phosphodiesterase 10A for chemoprevention and treatment of ovarian cancer. Poster Presentation at AACR Advances in Ovarian Cancer Research: Exploiting Vulnerabilities Meeting. October 17-20, 2015, Orlando, FL. M Patel, L Bachaboina, L Madeira da Silva, RP Rocconi, K Palle and JM Scalici. The Good, the bad, and the ugly: Estrogen Metabolites and Endometrial cancer risk. Poster Presentation at Society of Gynecologic Oncology 2016 Annual Meeting on Women’s Cancer. San Diego, CA. March 2016. SM Spencer, RR Somasagara, K Tripathi, L Bachaboina, JM Scalici, RP Rocconi and K Palle. Rad6 inhibition sensitizes ovarian cancer cells to platinum drugs by attenuating activation of multiple DNA repair networks. Featured Poster Presentation at Society of Gynecologic Oncology 2016 Annual Meeting on Women’s Cancer. San Diego, CA. March 2016. SK Srivastava, S Singh, JE Carter, L Madeira da Silva, JM Scalici, RP Rocconi and AP Singh. MYB: a novel player in pathobiology of ovarian cancer. Poster Presentation at Society of Gynecologic Oncology 2016 Annual Meeting on Women’s Cancer. San Diego, CA. March 2016. JM Scalici, JG Ross, L Madeira da Silva, W Nicolson, MD Harmon, S Boudreau, B Wang, MA Finan and RP Rocconi. Evaluating racial molecular complexity in gynecologic cancers. Poster Presentation at Society of Gynecologic Oncology 2016 Annual Meeting on Women’s Cancer. San Diego, CA. March 2016. JG Ross, KV Braswell, JM Scalici, L Madeira da Silva, F Mujica, S Stutsman, W Nicolson, MD Harmon, S Boudreau, B Wang, MA Finan, and RP Rocconi. Unraveling the etiology of ovarian cancer racial disparity in the Deep South: Is it nature or nurture? Poster Presentation at Society of Gynecologic Oncology 2016 Annual Meeting on Women’s Cancer. San Diego, CA. March 2016. L Madeira da Silva, JM Scalici, S McClellan, J Laurini, L Cruthirds, V Kolev, Y Li, I Shapiro, D Weaver and RP Rocconi. Standard chemotherapy for ovarian cancer increases expression of cancer stem cell biomarkers which is predictive of survival. Oral Presentation at Society of Gynecologic Oncology 2016 Annual Meeting on Women’s Cancer. San Diego, CA. March 2016. SK Srivastava, S Singh, A Bhardwaj, JE Carter, RP Rocconi, J Scalici, & AP Singh. Multiple functional implications of MYB in ovarian cancer. Submitted to AACR Annual Meeting, New Orleans, LA, April 2016. L Schambeau, L Amable, J Rocker, MA Finan, RP Rocconi, L Pannell. Relevance of albumin bound iron in ovarian cancer as determined by ICP-MS. Submitted to American Society for Mass Spectrometry Annual Meeting, San Antonio, TX, June 2016.


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III. INVITED PRESENTATIONS Finan MA. Invited speaker. USA Mitchell Cancer Institute Overview, Midtown Optimist Club - Azalea City Golf Course Clubhouse Meeting Room; Oct 6, 2015; Mobile, AL. Finan MA. Grand rounds speaker. The Nuts and Bolts of Resident Research; University of South Alabama Dept. of Obstetrics and Gynecology Grand Rounds. Oct. 30, 2015; Mobile, AL. Finan MA, Duplantis J. Invited speakers. Personalized Cancer Care. Gulf Coast Distinguished Lecture Series; Jan 21, 2016; Gulf Shores, AL. Finan MA. Invited speaker. USA Mitchell Cancer Institute Overview, Government Street Presbyterian Lunch Presentation; Feb 25, 2016; Mobile, AL. Finan MA. Invited speaker. Update in Gyn Oncology: Where we’ve been and where we’re going. The Twenty-Fifth University of South Alabama Obstetrics and Gynecology Conference; April 15, 2016; Daphne, AL. Finan MA. Invited speaker. MCI Update Presentation, Citronelle Cancer Support Group; Aug. 9, 2016; Daphne, AL. Finan MA. Invited speaker. USA Mitchell Cancer Institute Overview, Fairhope Rotary Presentation; Aug. 10, 2016; Fairhope, AL. Scalici JM. HPV Vaccine and Cancer Prevention: An Update for 2016. MCI Video Segment. Scalici JM. Grand rounds speaker. The Role of Estrogen & Metabolism in Gyn Cancers; University of South Alabama Dept. of Obstetrics and Gynecology Grand Rounds. Nov. 6, 2015; Mobile, AL. Rocconi RP.Grand rounds speaker. Surgical Management of a Pelvic Mass; University of South Alabama Dept. of Obstetrics and Gynecology Grand Rounds. Jan. 8, 2016; Mobile, AL.

IV. NATIONAL PROFESSIONAL RECOGNITION Dr. Michael Finan has been listed as one of the Best Doctors in America for more than a decade. He was also named among the Best Doctors by U.S. News and World Report from 2011 to 2015, and one of the best cancer doctors by Newsweek in 2015. He is a Diplomat for the American Board of Obstetrics and Gynecology, and a Fellow of the American College of Surgeons. He serves on the executive committee of the Society of Pelvic Surgeons. He is an author or co-author on dozens of peer-reviewed publications and has given presentations at national and international scientific meetings. He is actively engaged with the leadership at the University of Alabama at Birmingham in the development of a consortium partnership to allow MCI to gain NCI designation as a Comprehensive Cancer Center. Dr. Jennifer Scalici was awarded the 2015 Alpha Sigma Nu Magis Award for service. She is a Research member for the American Association of Cancer, a Candidate member of the Society of Gynecologic Oncology, a Fellow member of the American Congress of Obstetricians and Gynecologists, and a Board of Trustees member for Spring Hill College. Dr. Scalici was invited to serve on the NRG Oncology Cancer Prevention and Control Committee and is also an instructor for the GYN Oncology resident didactic conference. USA Mitchell Cancer Institute Annual Report

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Dr. Rodney Rocconi is a recipient of the Gynecologic Cancer Foundation Ovarian Cancer Research Award, the Gynecologic Oncology Group Young Investigator Research Award, and is an invited associate member of the NCI Early Detection Research Network. These experiences have allowed him to serve on numerous national leadership roles in the Society of Gynecologic Oncology, NRG Oncology Cooperative Group, NCCN, as well as chair certain U.S. Department of Defense Ovarian Cancer Research Program sections. He is a reviewer for Gynecologic Oncology, Cancer, Carcinogenesis, and the International Journal of Gynecologic Cancer, among other publications. Dr. Rocconi serves on numerous national committees including ACOG Alabama Chapter Advisory Board, NCCN Affiliate Research Consortium Leadership Committee, ASCO Gynecologic Cancer Guideline Advisory Group, NRG Oncology Translational Science in Gynecology Committee, and SGO Education Committee. In recognition of his accomplishments in oncology, he was selected to participate in the American Society of Clinical Oncology (ASCO) Leadership Development Program.

V. BRIEF SUMMARY OF ACTIVITIES AND PROGRESS Dr. Michael Finan serves as the cancer center director and is the Abraham A. Mitchell chair. He is also associate director for Clinical Affairs. He has worked on a research team with Dr. Rodney Rocconi and Dr. Lewis Pannell, focusing on a method for the early detection of ovarian cancer. This project uses pap smear fluid to identify a unique “fingerprint” of patients with early ovarian cancer, and the project is currently in the validation phase. It is funded by a $1.1 million federal grant and has resulted in six patent filings and a biotech spinoff company, Swift Biotech. One patent has been issued related to the technology. Dr. Finan is a member of the USA President’s Council and a member of the USA Health Medical Executive Committee. He volunteers as a police surgeon for the Mobile Police Department and is a member of Rotary Club of Mobile. Dr. Jennifer Scalici serves as Associate Professor, Interdisciplinary Clinical Oncology for University of South Alabama Mitchell Cancer Institute. She is also Staff Physician, Gynecologic Oncology Service for USA. Dr. Scalici is Director, Gynecologic Oncology Basic and Translational Research Lab at USA MCI overseeing the scientific, budgetary, and collaborative operations of a productive research laboratory. She is an Advisory Board Member for Camp Kesum, and a member of the Institutional Review Board and the Faculty Senate. Dr. Scalici serves on the Peer and Quality Review Committee and the Surgery Steering Committee for University of South Alabama Children’s and Women’s Hospital. She is also a member of the USA health system branding advisory board. Dr. Rodney Rocconi serves as professor and chief of Gynecologic Oncology and associate director for Clinical Research. He has a productive research career credited with more than 100 presentations at national meetings and more than 80 publications. His research interests include the molecular mechanisms of chemoresistance in ovarian cancer stem cells, as well as the genetic contributions of racial health care disparities in gynecologic malignancies. His research program is supported by multiple NIH/NCI and foundation grants. Under his leadership in Clinical Research, enrollment onto therapeutic studies has increased tenfold over the past four years. Importantly, this enrollment is enriched with minority patients (35 percent), which coincides with his research focus on disparities as well as an area of need for the MCI catchment area. He serves on numerous committees at MCI and the University of South Alabama, including the MCI Executive Leadership Committee, USA Faculty Senate and co-chair of the USA Clinical Research Committee.


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Summary of Scholarly Activities Medical Oncology


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“When I treat patients with cancer, I strive to provide hope. If feasible, I always aim for cure. That is the ultimate success.” – Dr. Moh’d Khushman, Assistant Professor of Interdisciplinary Clinical Oncology, staff medical oncologist

The year 2016 brought about expansion in Medical Oncology as we broadened our clinical reach to Monroeville and began work on a new site in Fairhope. We hired a national search firm to recruit a chief of Medical Oncology and began work toward a Medical Oncology Fellowship Program. Enhancing our services, we recruited Jessa Blount as the area’s first certified genetic counselor to work with patients and their families.


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I. PUBLISHED JOURNAL ARTICLES, BOOK CHAPTERS, AND PATENTS Azim S, Zubair H, Srivastava SK, Bhardwaj A, Zubair A, Ahmad A, Singh A, Khushman M, Singh AP. Deep sequencing and in silico analyses identify MYB-regulated gene networks and signaling pathways in pancreatic cancer. Scientific Reports. 2016;6:28446. Bhardwaj A, Srivastava SK, Singh S, Tyagi N, Arora S, Carter JE, Khushman M, Singh AP. MYB promotes desmoplasia in pancreatic cancer through direct transcriptional upregulation and cooperative action of sonic hedgehog and adrenomedullin. The Journal of Biological Chemistry. 2016;291(31):16263-70. Patel GK, Patton MC, Singh S, Khushman M, Singh AP. Pancreatic cancer exosomes: shedding off for a meaningful journey. Pancreatic. 2016;6(2):e148.

II. PUBLISHED ABSTRACTS Khushman M, Hosein PJ, Cameron D, Clarkson DR, Butler TW, Vu M, Wiseman-Norden C, Baliem W, Jones V, Bhadkamkar S, Nelson C, Lee F, Singh A, Taylor WF. Dihydropyrimidine dehydrogenase (DPD) and thymidylate synthesa (TYMS) germline pharmacogenomics role in predicting fluoropyrimidines toxicity in patients with gastrointestinal (GI) malignancies. Accepted for presentation as a poster in the ESMO 18th world congress on Gastrointestinal Cancer in Barcelona, Spain. Khushman M, Bhardwaj A, Patel GK, Laurini JA, Roveda K, Tan M, Singh S, Taylor W, Singh AP. The pattern of exosomal marker (CD63) expression using immunohistochemistry (IHC) in malignant and non-malignant (normal, inflammatory and pre-malignant) ductal cells in resected pancreatic tissues. Accepted for presentation in the AACR special conference on pancreatic cancer. Khushman M, Patel GK, Bhardwaj A, Srivastava SK, Khan MA, Singh S, Brandt B, Taylor W, Singh AP. The role of exosomes in promoting acquired resistance to gemcitabine and nanoparticle albuminbound (NAB) paclitaxel in pancreatic ductal adenocarcinoma cells. J Clin Oncol 2016;34:e23253. Khushman MM, Hosein PJ, Cameron D, Clarkson DR, Butler TW, Vu M A, Wiseman-Norden C, Baliem W, Jones V, Bhadkamkar S, Nelson C, Lee F, Singh A, Taylor WF. Germline pharmacogenomics in patients with dihydropyrimidine dehydrogenase (DPD) deficiency. Presented as a poster in the 2016 GI ASCO meeting. Patel GK, Bhardwaj A, Srivastava SK, Kahn MA, Singh S, Patel GK, Khushman M, Singh AP. Chemotherapy-induced exosomal secretion promotes chemoresistance in pancreatic cancer cells. Presented as a poster in the 2016 AACR meeting.


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III. INVITED PRESENTATIONS Butler T. Annual Meeting on Supportive Care in Cancer, Multinational Association of Supportive Care in Cancer, Adelaide, Australia

IV. NATIONAL PROFESSIONAL RECOGNITION Khushman M. Consultant, Molecular Oncology Advisory Board Khushman M. Consultant, Long Term Management of Patients with aHUS Advisory Board Khushman M. Workshop, Fundamentals of Clinical and Translational Research (FaCToR) On-line workshop. Harvard Catalyst (January 2016 – April 2016)

V. BRIEF SUMMARY OF ACTIVITIES AND PROGRESS Averett C, Bhardwaj A, Arora s, Srivastava S, Ahmad A, Khan MA, Singh S, Carter J, Khushman M, Singh AP. Honokiol suppresses pancreatic tumor growth, metastasis and desmoplasia by interfering with tumor-stromal cross-talk. Submitted to Carcinogenesis. Butler T. Presenter, OSTOMY group Butler T. Presenter, Supportive Care and Cancer Forum Butler T. Presenter, MCI Lunch and Learn Cameron D. Leader, OSTOMY group Cameron D. Presenter, OSTOMY group (2 sessions) Cameron D. Presenter, Breast cancer, Monroe County Hospital Khushman M, Morris M, Diaz L, Garcia-Buitrago M, Zelaya S, Nayer A, Moshiree B, Fuller K, Pereira D. Goodman M, Komanduri K. Syndrome of inappropriate anti-diuretic hormone (SAIDH) secondary to strongyloides stercoralis infection in all allogeneic stem cell transplant patient: Case report and literature review. Submitted to Transplant Proceedings. Scherfenberg N, Khushman M, Carcas L, Blieden C, Vega F, Hosein P, Swords R. Acute myeloid leukemia with translocation (8;16)(p11;p13): a distinct syndrome – case report and literature review. Submitted to Clinical Case Reports Journal.


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Khushman M, Hosein PJ, Cameron D, Clarkson DR, Butler TW, Vu MA, Wiseman-Norden C, Baliem W, Jones V, Bhadkamkar S, Nelson C, Lee F, Singh A, Taylor WF; Dihydropyrimidine dehydrogenase (DPD) and thymidylate synthesa (TYMS) germline pharmacogenomics role in predicting fluoropyrimidines toxicity in patients with gastrointestinal (GI) malignancies. Khushman M, Bhardwaj A, Patel GK, Laurini JA, Roveda K, Tan M, Singh S, Taylor W, Singh AP. The pattern of exosomal markers (CD63 and CD9) expression using immunohistochemistry (IHC) in malignant and non-malignant (normal, inflammatory and pre-malignant) ductal cells in resected pancreatic tissues. Khushman M. The pattern of exosomal marker (CD63) expression using immunohistochemistry (IHC) and its prognostic and predictive role in patients with pancreatic adenocarcinoma. Khushman M. The role of exosomes in promoting acquired resistance to gemcitabine and nanoparticle albumin-bound (NAB) paclitaxel in pancreatic ductal adenocarcinoma cells. Khushman M. Erythroblastemia in patients with GI malignancies. Khushman M. Co-Investigator: A phase I study evaluating the safety of single-fraction high-dose LATTICE radiotherapy followed by chemotherapy, immunotherapy and low dose immunogenic radiation therapy for bulky stage III and IV non-small cell lung cancer. Norden C. Member, NAPBC Breast Program Leadership Committee. Norden C. Principle Investigator, Clinical trials for breast cancer. Taylor W. Principle Investigator, Stage II colon cancer. Project for Cancer Committee. Taylor W. Ongoing evaluations of stage III colon cancer – adherence.


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Summary of Scholarly Activities Radiation Oncology


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“I feel like the best thing I can do is help patients understand where they are in the process. Providing them with that education helps them have a level of control over what’s going on.” – Clayton Smith, M.D., Ph.D., Assistant Professor of Interdisciplinary Clinical Oncology, Staff Radiation Oncologist This year we expanded and reorganized the Radiation Oncology department. A new radiation vault was constructed, allowing us to add a linear accelerator to our treatment offerings, including the only CyberKnife precision radiosurgery in south Alabama, which allows for the treatment of prostate cancer in five sessions with no surgery and minimal side effects. Three radiation oncologists joined our team, Dr. Clayton Smith, Dr. Weisi Yan and Dr. Elesyia Outlaw, who trained at institutions such as Cornell, Vanderbilt and Washington University in St. Louis. USA Mitchell Cancer Institute Annual Report

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I. PUBLISHED JOURNAL ARTICLES, BOOK CHAPTERS, AND PATENTS Galle JO, Chilukuri MB, Buckley SL, Hall MJ, Wilcox LR, Ove R. Tolerance of Superficial Dose to Setup Error With Tomotherapy: Is a Skin Flash Tool Required? Technology in Cancer Research & Treatment. 2016 June;15(3):411-415 Pella S, Bacala A, Chilukuri MB, Planning and Delivering HDR APBI Treatments (Quality Assurance and QMP for Brachytherapy Treatment Delivery and Treatment Planning System). Med. Phys. 2016;43:3776

II. PUBLISHED ABSTRACTS Parker CA, Ove R, Chilukuri MB, Russo SM. Monte Carlo Dosimetry Evaluation of Lung Stereotactic Body Radiosurgery. ONCOLOGY, ARS 2015, Proceedings of the 97th Annual Meeting of American Radium Society. Smith CA, Sekhar KR, Crooks PA, Traver G, Freeman ML. (2016). Targeting ENOX1 Impairs Repair of DNA DSBs in Endothelial Cells and Increases Survival in Tumor-Bearing Mice. American Society for Radiation Oncology Oral Poster Presentation.


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III. NATIONAL PROFESSIONAL RECOGNITION Clayton A. Smith, M.D., Ph.D. American Society for Radiation Oncology Resident Clinical/Basic Science Award in Biology – September 2016

IV. BRIEF SUMMARY OF ACTIVITIES AND PROGRESS Madhu B. Chilukuri, Ph.D., DABR Has taught Dosimetry class RAD455 at Department of Radiologic Sciences, Pat Capps Covey College of Allied Health Professions at University of South Alabama every spring semester for past 4 years. Has served on the Advisory Committee of the Department of Radiologic Sciences at University of South Alabama. Has served on the Radiation Safety Committee at University of South Alabama for past Nine years. Installed, accepted and commissioned the TOMO Edge upgrade to our existing Tomotherapy machine. Commissioned the treatment planning unit too. Upgraded the Cyberknife system and recommissioned the IRIS collimator and recommissioned the Multiplan treatment planning system with IRIS and Monte Carlo dose calculation algorithms. The Varian IX was decommissioned from the Infirmary site and installed, accepted commissioned the IX at new extension to MCI. The Eclipse planning station was also recommissioned with the latest dose calculation algorithms. New patient specific QA procedures are being implemented on the Tomotherapy and Cyberknife units. The radiation therapy section is pursuing the American College of Radiology (ACR) accreditation process and the physics team is playing a crucial role in making sure the physics policies and procedures are in place and the QA is being performed and documented as per the ACR guidelines. Clayton A. Smith, M.D., Ph.D. Joined faculty as Assistant Professor of Interdivisional Clinical Oncology in the Department of Radiation Oncology in July 2016.

Brian H. Ward, Ph.D.


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The USA Radiation Oncology department has gone through a number of changes recently. A number of those changes involved upgrades to the therapy treatment machines and ancillary equipment. During the last year, medical physics has been a vital part of those upgrades, as well as making contributions in patient quality assurance and in teaching courses to USA radiological science students. My colleague, Dr. Madhu Chilukuri and I were involved in the Tomotherapy® linear accelerator upgrade and the accompanying treatment planning software upgrade. Re-commissioning of the accelerator and data verification were performed. The CyberKnife® linear accelerator also had an upgrade and the treatment planning software for Monte Carlo and Iris dose algorithms had to be recommissioned. The Varian iX® linear accelerator was re-commissioned after being moved to a new location. Physics was involved in beam data collection and analysis. The Varian Eclipse® treatment planning software also had to be re-commissioned, which physics completed. Currently, new patient specific quality assurance tools for the Tomotherapy®, CyberKnife® and Varian iX® linear accelerators are being implemented; specifically the Sun Nuclear ArcCheck® system is being commissioned for use. During the fall semester of 2015, I taught RAD 448, Radiation Therapy Physics, to students pursuing a bachelor of science in radiological science. I am currently teaching RAD 448 this semester, as well. The USA Mitchell Cancer Institute, Department of Radiation Oncology, is pursuing American College of Radiology (ACR) accreditation. As one of the physicists in the department, I am responsible for making sure physics policies and procedures are in place. Also, physics is responsible for performing and documenting quality assurance procedures per the ACR guidelines. Weisi Yan, M.D., Ph.D. A phase I study evaluating the safety of single-fraction high-dose LATTICE radiotherapy followed by chemotherapy, immunotherapy and low dose immunogenic radiation therapy for bulky stage III and IV non-small cell lung cancer.


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