Preface to Series - ATS Journals

Airway Epithelium, Inflammation, and Mechanisms of Disease: A Tribute to Carol B. Basbaum Preface to Series This series of the American Journal of Respiratory Cell and Molecular Biology, “Airway Epithelium, Inflammation, and Mechanisms of Disease: A Tribute to Carol B. Basbaum,” is dedicated to the memory of Carol Basbaum, who passed away in April 2005 after a long and courageous battle against ovarian cancer. One might ask why the editors of the Journal decided to go forward with this unprecedented tribute. There is no question that Carol Basbaum was a brilliant scientist who had an international reputation in the area of airway biology, inflammation, and mucus. Anyone could look at her CV and see the objective evidence of this: over 100 peer-reviewed papers in the best journals, continuous R01 funding from NIH for decades, invited presentations and invitations to chair sessions and serve on organizing committees, editorships and service on editorial boards, and a long history of training and mentoring students, post-docs, and residents. She made seminal findings in airway pathobiology and was considered the preeminent scientist in the field. She was the first to describe plasticity of airway epithelial cells, the first to culture serous cells from airway submucosal glands, the first to introduce MUC2 to airway cell biology, the first to clone the MUC5AC promoter, the first to show the significance of MAPK signaling in regulation of airway mucin expression, the first to introduce ADAM/TACE and EGFR signaling, among many other contributions. She was one of the original Associate Editors for the AJRCMB and served on the Editorial Board after her 5-year term was over. But there are many outstanding scientists in respiratory biology with similar levels of achievement. What set Carol apart was her personal, human side that pervaded all of her interactions with colleagues and friends. When I set out to create this special series for the Red journal, I asked a number people in the field of airway epithelium and mucus if they would contribute by writing a review article. I was overwhelmed not only by the positive response from all, but even more so by the unanimous response along the lines of “Carol helped me so much in my career that I would be honored to contribute.” Carol touched so many people and was such a positive force in the development and professional success of countless individuals in pulmonary research. The tributes and remembrances below speak to this part of her persona. Obviously, if I had asked all of the many colleagues, coworkers, and friends of Carol to take part in this tribute, there could be tens if not hundreds of individuals involved. Due to space limitations, however, I was only able to request tribute paragraphs from authors of the review articles in this series that are related to airway epithelium and mucus, which will appear in this and the next few issues of the Journal. I sincerely apologize to those who knew Carol and were not asked to contribute for the above reasons. To me, Carol was a dear friend and colleague. She was—and I would remind her of this continually—one of the smartest people I know. I think that everybody in this business is “smart,”

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Carol Beth Basbaum (1946–2005) but Carol had profound perspectives on scientific issues that reflected the depth of her knowledge and scientific acumen. As with others, she helped me scientifically and professionally in so many ways: if I got an idea, I’d run it by Carol; if I had a question or needed scientific advice, she was the first person I’d ask, and she was always glad to help; and this is something that I’m sure was true for everyone who contributed to this series. I remember telling Carol on many occasions that she was probably “too smart” sometimes and that her priority scores on grants probably were 20 points worse than they should have been because of this, because things that were obvious to her might be out of the realm of quick understanding by reviewers. Carol was honest, sincere, and surprisingly funny . . . I still have a long list of e-mails she sent me, jokes, bizarre things, etc. In addition, she was truly one of the nice people in this business . . . she never had a bad word to say about anyone. Carol was a few years ahead of me and was already a wellestablished “name” in the field when I met her for the first time; I was still a graduate student when she came to one of my posters at a national meeting and asked me some questions. Many years later, she told me she remembered that and thought at the time I was “curt” to the point of being impolite. What I never told her was that as soon as I saw her name tag I was petrified that this famous scientist was going to embarrass or humiliate me in public, and I just wanted her to go away. If I had known at that time who Carol Basbaum really was, and of the grace and class with which she comported herself throughout her life, I would have realized how unfounded and absurd those fears were. Kenneth B. Adler, Ph.D. Deputy Editor, American Journal of Respiratory Cell and Molecular Biology

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As a nervous junior investigator invited to a prestigious conference, I had survived a long plane ride with a hefty trip by car yet to go. It was approaching midnight and the person in front of me at the rental car dealer was told that she had not made reservations. I recognized her as the famous Carol Basbaum. It seemed odd that she would not properly rent a car, but I thought I would introduce myself and offer her a ride. However, I was informed that I did not reserve a car either. It became apparent that they did not have any cars left. I was fuming (a supervisor had to restrain me from the arrogant ___); Carol, however, remained understanding and collegial. She found out that they had one pick-up truck left, and hence I met Carol driving a pickup down the Florida coast after midnight. From that point on, Carol was a true friend and colleague, providing me with insight into science and frank career advice, some that I didn’t always want to hear but always appreciated. Academic medicine is a strange and wonderful career, especially when it allows us to meet special people in the strangest of circumstances. Steven D. Shapiro, M.D. Editor, American Journal of Respiratory Cell and Molecular Biology When I went to work in Carol’s laboratory in 1985, one of the first things I realized was that she treated people in her lab like colleagues, and not like employees. As time went on, I also realized that she was one of the most principled and honest people I had met in my short scientific career; and now, 20 years later, that still holds true. She did not let us get away with any shoddy data or illogical thinking. She had a saying when one of us tried to stretch things a little too far: “True—True—but Unrelated.” She also did not want us to do “unauthorized experiments”—unless of course they worked, in which case you were forgiven. I guess we made a good pair because she could spell (I couldn’t), she never cursed (I did), and she hated computers (I don’t). She was my mentor, confidant, and hero, but most of all, my friend. Marianne Gallup, B.A. University of California, San Francisco San Francisco, California When thinking of Carol, the immediate question I have is “what has she not done in her scientific career for our small research community in the field of mucin and airway cell biology?” I looked in PubMed under “Basbaum C” this morning; there are 117 peer-reviewed papers listed, and even in 2006, she has a paper in our Red journal on the mechanism of bacterial infection. We had a very similar path in our career and very similar passion on certain research topics. However, her research is much broader and deeper, with greater accomplishment. She has done so much excellent work in lung epithelial cell biology, cancer, bacterial infection, mucin gene cloning, lysozyme cloning, cytokines, gene expression, transcriptional mechanisms, signal transduction, tobacco smoke, protease, and in many other areas. I remember she told me that she was not afraid of criticism or competition. She knew we were “competing” with each other, yet we still had joint lab meetings. I remember the most dramatic was the meeting at her lab during the 9/11 tragedy. We were sorrowed about our nation under attack and the loss of many lives, but we also sensed a duty to complete the meeting as planned in defiance of the fear and the sorrow. She always was a fighter, and not one to quit easily. I remember visiting her lab only two years ago. She was right there, working in the lab, and I was shocked to learn that she has just undergone a major operation related to the cancer she was fighting. She calmly told

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me, “it is just an experiment.” Toward the end, I grew extremely sad for the loss of such a fighter and competitor, and the most brilliant scientist in our field. I am not sure anyone can replace her. Reen Wu, Ph.D. University of California at Davis Davis, California Carol was a mentor and good friend. It was my great privilege to have known her well for more than 15 years. She was an amazingly open, friendly, and helpful person, which I would say is rare among the highly competitive, elite scientific company she kept. She had a quirky and irrepressible sense of humor, easily bringing a smile and a laugh. Who else would have been happy to be labeled the “queen of mucus” in her obituary in the San Francisco Chronicle? Behind her playful exterior was a driven worker, mentor, and collaborator. Many, many students, fellows, post-docs, and collaborators benefited immensely from knowing and working with Carol. Carol’s lab was an extended family—she loved them and they loved her in return. Carol fought a courageous battle against ovarian cancer for many years, yet her scientific productivity actually increased after her diagnosis. A few years ago, I visited her laboratory, and after lunch, despite massive doses of potent chemotherapy that her body had endured, and despite resistant tumors that would not go away, she just charged back up one of those steep San Francisco hills, leaving her younger, healthy colleague out of breath. Her spirit and courage were inspiring. Carol served on NIH study sections, the ever-present advocate for good work on airway epithelium . . . even after surgery to remove a large metastatic tumor from her brain. When the ATS meets again in San Francisco in 2007, Carol will not be there to host a big, fun party at her home for her many friends and colleagues, or intimate dinners with good friends, as in years past. How ironic it is that her marvelous and positive personal traits make us miss her so much. Scott H. Randell, Ph.D. University of North Carolina at Chapel Hill Chapel Hill, North Carolina My first encounter with Carol was nearly 30 years ago when we were both trying to start a career in research—she as a professor and I as a fellow/instructor. I remember those days as though they just occurred. In particular, I remember Carol. She was part of an extended CVRI family that was working on various aspects of airway diseases, and she had taken on the mucous cell. She was especially skilled in the cell biology of epithelial cells and secretion. At the time, even the term “cell biology” was a little foreign to lung research, let alone a focus on airway secretory cells. Given what happened to this field and lung research in general, Carol was ahead of her time and stayed that way. But, what struck me in those early days and ever since was the genuine and gentle nature of Carol as scientist and friend. She was bright and creative, but, in an unusual combination, she was also sweet, honest, and forthright. She offered the kind of rare role model that is so hard to find for women and men who want to excel in research and still be great partners, parents, friends, and colleagues. Carol symbolized what is good in science and in the world. Michael J. Holtzman, M.D. Washington University in St. Louis St. Louis, Missouri

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As a graduate student working with Drs. Allison Fryer and David Jacoby at Johns Hopkins, I had the opportunity to meet Carol when she was there as a visiting professor. I had the opportunity to briefly summarize work I was doing, investigating the role of eosinophil MBP in neuronal M2 muscarinic receptor dysfunction and airway hyperresponsiveness. Having little training at that time, when she asked me what the mechanism of MBPmediated M2 dysfunction was, I remember quickly drawing a stick-figure nerve terminal with a circle (MBP) drawn on top of a rectangle (M2 receptor), and authoritatively stating, “It blocks it, see.” Though unamused, she charitably allowed me to have my say, and left me unbesmirched without really letting me know how clueless and sophomoric she could tell I was. Luckily, David was able to quickly intercede, by more accurately (and less “authoritatively”) explaining to Carol that MBP is an allosteric M2 receptor antagonist. Many years later, with trainees of my own, I can now appreciate the patience she must have developed during her academic journey. Christopher M. Evans, Ph.D. MD Anderson Cancer Center Houston, Texas It was my privilege to know Carol Basbaum for over 20 years. She had just been promoted to associate professor when I began my Pulmonary Fellowship at UCSF. Although I did not work with her directly, I learned most of what I know about mucus from her. I sent several graduate students and fellows from Johns Hopkins to work with her, knowing they would be well trained and mentored, and treated well. But my enduring impression of Carol is that for all her achievements, she was always modest and unassuming, polite, and considerate. Her gentle humor was directed as much at herself as at her colleagues and students. What I will miss most about her is a personality and character too uncommon in science. David B. Jacoby, M.D. University of Oregon Health Sciences Center Portland, Oregon I first met Dr. Carol Basbaum at a Transatlantic Airway Conference she was chairing. At that time, I was a beginner post-doc and was impressed by the ability of this young investigator to coordinate and direct the meeting and make this task look so easy. In addition to her unique skills in interacting with scientists around the world, she was encouraging to all young scientists, and in part it was her encouragement that helped me survive when I started writing grants and initially struggled with nonfundable scores. It was in her nature to help new ideas develop even when they are prone to many criticisms at early stages. Later, when I was preparing for another grant as part of an SCOR program, she came all the way to Albuquerque to participate in our internal review. When she arrived, I was astonished to find out that she was undergoing chemotherapy after being diagnosed for cancer. This incident shows one aspect of Dr. Carol Basbaum’s legacy—her dedication to advance scientific research and help out wherever she was needed. Yohannes Tesfaigzi, Ph.D. Lovelace Research Institute Albuquerque, New Mexico Carol promulgated what clinicians, patients, and relatives of patients know: that mucus matters when there’s too much of it and when it doesn’t move. She strove to understand the molecular basis of how the mucin genes work, thereby moving the mucin/mucus field forward and integrating it into the larger field

of inflammation and lung biology. Perhaps the premier example of Carol’s insight and vision in this field is the program she put together for the Novartis Foundation meeting in March of 2002. At that time, Carol was already dealing with her “medical problem,” a fact known to all but never acknowledged. She went out “with her boots on,” and I can’t imagine her wanting it any other way. Mary C. Rose, M.D. George Washington University Washington, D.C. Carol was obviously an expert in cell signaling and mucin secretion and this was apparent not only in her publications, but also in her candor and expertise as a grant reviewer. I first got to know her during our initial appointments on the Lung Biology and Pathology study section almost 20 years ago where we were among the only women in a room of men who would talk about tennis or basketball after science. At first we didn’t participate, but since watching the NBA championships was a must every June after the review sessions, we joined the group to watch the games, finally realizing (thanks to Guy Zimmerman) that the Utah Jazz was not a group of musicians! As expressed by Reen Wu in a session in which I (with his help) won the “rubber ball” award, “mucin people stick together.” Carol will be missed by all of us. Brooke T. Mossman, Ph.D. University of Vermont Burlington, Vermont We first met at grant review sessions where Carol was a great champion of good science and particularly of young investigators. She would ferret out the good ideas, rewording the investigator’s intent if necessary to strengthen the application. She was always the one to give the applicant the benefit of the doubt, seeing potential strengths and the ultimate goals while the rest of us were mired down in a few, probably trivial, faulty chains of logic. We argued often and long over numerous details of epithelial cell biology; how her experimental system differed from mine, and how specific issues should be correctly addressed. Reagents and post-docs were sent cross-country and a very fruitful collaboration ensued. Our long-standing academic debates were often pleasantly resolved during long walks that ended at ice cream counters, over a glass of wine, or at a fabulous restaurant. Invariably optimistic, she pushed herself, and by example, those around her, to work a little harder and to seek higher goals. Alice Prince, M.D. Columbia University New York, New York I first met Carol nearly a decade ago when she visited the UC Davis campus to give a talk as part of a respiratory research conference series, and we subsequently interacted during joint lab conferences with Reen Wu’s laboratory. At that time I was trying to become an independent researcher, and I remember having a good discussion with her about my research project in squamous metaplasia, as she was interested in that area as well as in mucous differentiation, since these two processes are inversely related. In more recent years I frequently shared conversations with Carol at ATS meetings, where I appreciated receiving her helpful input with regard to my research work. She always impressed me with her intelligence, her forthrightness, and her perceptive criticisms. After moving to Johns Hopkins I maintained a strong collaboration with Carol’s group, particularly

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with Nancy McNamara, since this group is interested in the transcriptional regulation of SPRR1B by cytokines and its role in lens epithelial differentiation and keratinization. I am going to miss Carol and will always be grateful for the support and input that she has given me over the years. Sekhar P. Reddy, Ph.D. Johns Hopkins University Baltimore, Maryland All her colleagues will remember Carol Basbaum for leading a long and very productive career in the field of airway cell biology/ physiology, but an example may better illustrate this point. Although Carol and I shared the same birth year, 1946, her first paper, on the localization of Na⫹ pumps in tracheal epithelium with J. H. Widdicome and J. Y. Lee, was published in 1979, exactly 10 years before mine on Na⫹ fluxes across cultures of Clara cells with M. R. Van Scott and R. C. Boucher. By the time my laboratory’s first paper on mucin secretion from goblet cells appeared in 1992, Carol had already published extensively in such areas as the innervation of submucosal glands, mucin and glycoconjugate biochemistry, regulation of gland mucous and serous cell secretion, and submucosal gland development, and she was just beginning her work on the molecular biology and regulation of secretory cell gene expression. The breadth of her interests spanned airway cell biology; she was a “pioneer” in the truest sense of the word. Over the past 14 years, including the last five as she courageously battled her disease, Carol made numerous contributions, continuing her work on the regulation of mucin gene expression and extending it into such areas as infection, inflammation and environmental effects in the airways, and bacterial–epithelial cell interactions. She contributed so much to research in cystic fibrosis that the CF Foundation has named their top fellowship award in Carol’s honor.

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For all of us in the field now, and for those to come, Carol will continue to live through the expression of her work in the existing literature. What we will miss, because it can’t be expressed in print, is her collegiality, her encouragement of rigorous work and sense of fair play, her welcoming demeanor and sense of humor, and her friendship. For in addition to being a pioneer in our field, Carol was also a leader in the truest sense of the word: She was very active in our community, always stimulating new research, promoting rigor, and leading by example. We miss you, Carol. C. William Davis, Ph.D. University of North Carolina at Chapel Hill Chapel Hill, North Carolina Carol Basbaum was a treasured member of the faculty in the Cardiovascular Research Insititute (CVRI) at the University of California, San Francisco for many reasons. First, she was an outstanding scientist who made major contributions to airway mucin research and related areas of airway pathophysiology. Second, she was a generous scientist who was always open to collaborations and exploring new ideas with junior faculty as well as research fellows. Third, she had outstanding human qualities that made her approachable, friendly, and a valued colleague for all of us. I also served with her on a NHLBI study section and I can attest to her superior qualities as a scientific reviewer. We miss her very much here at the CVRI and at UCSF, but her memory lives on. Michael A. Matthay, M.D. University of California, San Francisco San Francisco, California DOI: 10.1165/rcmb.F311