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• W3203048222 abstract "Dr. Paul S. Frenette, M.D. passed away on July 26th, 2021 at the age of 56. He was an extraordinarily clever, compassionate, and collegial physician scientist. He was a stalwart champion for medical research and for ensuring translation of his discoveries to the clinic for the benefit of patients with intractable medical conditions, including acute myeloid leukemia, prostate cancer, and sickle cell disease. He was revered for his creative, rigorous paradigm-shifting science and loved for his kindness, humbleness, and humor. Paul will be dearly missed by his family and friends. He adored his wife Nadine and their children Clara and Albéric. He was so proud of their accomplishments and was looking forward to watching their journeys into college and life. He glowed when he would talk about his family. We extend the deepest and heartfelt condolences to them as well as his siblings, his current and former trainees, colleagues, and friends as we all mourn this monumental loss. Although a New Yorker for over two decades, Paul was originally from Québec City, Canada and was raised in a loving family with two brothers and two sisters. Here he acquired his love of skiing and hockey. He began his medical journey at Université Laval with subsequent training at McGill University and the New England Medical Center. In Boston, Paul truly found his love and aptitude for science as well as the love of his life, his wife Nadine. In 1998, Paul was recruited by Barry Coller to Mount Sinai School of Medicine to start his own lab and eventually joined the Einstein faculty in 2010 as a professor of medicine and cell biology and the inaugural director and chair of the Ruth L. and David S. Gottesman Institute for Stem Cell Biology and Regenerative Medicine. His research achievements, leadership, and mentoring commitment over the years have been truly exceptional and are widely recognized both nationally and internationally (Figure 1). His lab’s early work on selectins led to transformative treatments for vaso-occlusion in patients with sickle cell disease (SCD) (Turhan et al., 2002Turhan A. Weiss L.A. Mohandas N. Coller B.S. Frenette P.S. Primary role for adherent leukocytes in sickle cell vascular occlusion: a new paradigm.Proc. Natl. Acad. Sci. USA. 2002; 99: 3047-3051Crossref PubMed Scopus (337) Google Scholar). Paul built on this finding not only from a basic science perspective, but with an eye on how to help improve the lives of patients who suffer so much. He worked closely with physicians and drug companies to foster this finding into meaningful action, which culminated in the 2019 approval of an anti-P-selectin antibody for the treatment of SCD vaso-occlusion. Due to his attention to detail, Paul’s group made another unexpected seminal discovery that the nervous system regulated hematopoietic stem cell (HSC) behavior (Katayama et al., 2006Katayama Y. Battista M. Kao W.M. Hidalgo A. Peired A.J. Thomas S.A. Frenette P.S. Signals from the sympathetic nervous system regulate hematopoietic stem cell egress from bone marrow.Cell. 2006; 124: 407-421Abstract Full Text Full Text PDF PubMed Scopus (973) Google Scholar; Méndez-Ferrer et al., 2008Méndez-Ferrer S. Lucas D. Battista M. Frenette P.S. Haematopoietic stem cell release is regulated by circadian oscillations.Nature. 2008; 452: 442-447Crossref PubMed Scopus (883) Google Scholar). This work thrust him to the forefront of the HSC niche field where he quickly became a rising star and leader. Paul had a way of elevating those around him. His focus and work ethic are embodied in a phrase he shared often with his longtime administrator Joan Pitcan, “Get it done.” Paul was not about excuses, but solutions. He would challenge his trainees to find solutions to difficult but critical scientific questions. Similarly, science, hard work, and respect were at the forefront as he developed the Stem Cell Institute at Einstein. His out-of-the box approach to science will live on in his trainees, who know that they are better scientists for having worked with him. He challenged his trainees to think deeper. He was often right, but he would “bet them a beer” to prove him wrong. Let us all raise a glass to the eminent Dr. Paul Frenette. Paul was an outstanding hematology fellow in my laboratory in the nineties and after that a long-term collaborator and friend. He had little lab experience when he joined my group, but this was compensated for by great courage and intelligence. He wished to learn the new knockout mouse technology and decided to begin by preparing a double knockout of P-and E-selectin genes located very close to each other. This meant modifying a preexisting embryonic stem cell lacking P-selectin a second time, which had not been done before. My objections that such overmanipulated cells may not get incorporated into the germline, and that a mouse without both endothelial selectins may not live, were promptly dismissed. The three-year project, in collaboration with Tanya Mayadas and Richard Hynes (MIT), produced a very interesting mouse whose hematological phenotype was described by Paul in Cell (Frenette et al., 1996Frenette P.S. Mayadas T.N. Rayburn H. Hynes R.O. Wagner D.D. Susceptibility to infection and altered hematopoiesis in mice deficient in both P- and E-selectins.Cell. 1996; 84: 563-574Abstract Full Text Full Text PDF PubMed Scopus (448) Google Scholar). This work established that selectins mediate leukocyte rolling in vivo. Paul also deduced that platelets and leukocytes have more in common than anyone had anticipated. Paul continued to produce exciting, unexpected observations throughout his career. It breaks my heart that it ended early; mentees are not supposed to leave before their mentors. Paul’s work resulted in a paradigm shift in the understanding of SCD and energized a field that had been searching in vain for novel therapies for over 50 years. He was the first to identify the critical role of neutrophils and heterocellular adhesive interactions in SCD pathophysiology. While there were initially many detractors of this model, the translation of these observations in the clinic has already profoundly changed patients’ lives. I knew Paul as a collaborator, a dear friend, and a role model. Paul was a tremendous scientist, but above all he was an exceptional person with the highest integrity. He cared deeply about the accuracy and quality of his scientific work, and this was his North Star. This, I think, informed his remarkable focus and intensity in moving projects forward and navigating any difficult professional interactions with clarity, ease, and grace. He was generous with his time and guidance, trusted people easily, smiled readily, and was always authentic. He was deeply affected by the suffering of the patients with SCD and once said to me that it was “enough” and he needed to find a way to make SCD better. The field has lost a tremendous champion. I will miss him deeply. Paul has been an invaluable member and frequent speaker on the conference circuit of the cancer, hematology, and stem cell fields. His innovative and pioneering research and critical contributions to discussions at conferences have greatly influenced the development of these fields in numerous directions. A proud French Canadian, Paul’s sharp mind, dry humor, and charm were much appreciated during conference dinners, receptions, and scientific discussions among colleagues. He was also fond of the arts and enjoyed visiting exhibitions surrounding the conferences. Paul was an enthusiastic skier who could always be found on the slopes during breaks at Keystone conferences and was always up for a little fun racing. As a connoisseur of red wine and especially champagne—preferably Dom Pérignon—he was not averse to sometimes making scientific bets on a good bottle. Paul will be sorely missed in the conference world and beyond, not only as a mentor and stimulus for new scientific developments, but also as a colleague and friend with his gracious, jovial, and inspiring personality. I mourn the loss of one of my best friends. When I first met Paul, it was in New York City at a conference. Instead of taking me to a stylish restaurant, he brought a box of sandwiches and took me to Central Park, where we sat on a stone and enjoyed lunch. We talked frankly and casually without any formalities. In science, he was serious and careful. At the same time, he was also a man who knew how to enjoy and appreciate a life. He was good humored and interested in different cultures and traditions. Besides science meetings, I had numerous and precious opportunities to share time with Paul. Once, we went to the Tsukiji Fish Market at 5 a.m. to see the tuna auction. Paul was so impressed, and after the auction we ate sushi with the fishmongers. On another occasion, we went to sumo wrestling. Paul was so excited and asked me so many questions; many of them I could not answer even though I know quite a bit about sumo. I miss his radiant smile, which delighted me. Not only have we lost a great scientist, but I have lost a good friend. Please rest in peace. The day I learned Paul had slipped away from us was the saddest, and probably the toughest, day I have ever spent at Einstein. I vividly remember that after I signed the offer letter from Einstein 10 years ago, Paul took my wife and I to his favorite restaurant, JoJo, where he spoke passionately about the Institute’s future and how together we would expand the scope of stem cell research at Einstein. I have countless beautiful memories of Paul. I clearly remember one particular miracle: for a west coast conference, we scheduled completely different flights at different airports with departures hours apart. We said, “See you later in LA!” as we set off separately from Einstein. But due to my flight experiencing delays, we found ourselves exiting back-to-back taxis at the same moment as we arrived at the conference. We laughed then that this only confirmed “it was destiny for us to become colleagues at Einstein!” I so enjoyed the time we spent organizing symposia, retreats, and other activities. After hours, we shared so many memorable dinners, with Paul always picking the perfect wine. My office was situated directly across from Paul’s, and I chatted with him whenever we crossed paths as if he were my nearest brother, and Paul just as often stopped by my office to enjoy a cup of coffee with me. We pondered, discussed, and argued over a wide range of topics, from key attitudes as a PI to the latest ice hockey news. There is no question that Paul is a pioneering scientist and his contributions to the field have been exceptional. But it was his wonderful personality that won me over as a friend. I want to emphasize how fortunate I was to have Paul as my role model and faculty mentor. He always offered sound advice, kept me on the right track, and helped me initiate and sustain a successful independent career. Paul will deeply be missed. Paul was always there, like a friend, for his trainees, staff and fellow faculty. As a faculty member, I often went to him with questions and problems on grants, lab affairs, paper submissions, and more. I could talk to him so openly, like he was an older brother. He had nurtured this environment in the institute which was not just for performing high-caliber science but also for building those strong bonds and friendships. That is why losing him so suddenly has been so tough. It was a privilege and luxury to have a scientist so brilliant, kind, and caring on my side. He was instrumental in getting my independent academic career started and helping me grow as a scientist. He was sharp and practical, but more importantly a good-hearted and simply good human being. I will deeply miss his sense of humor and our many banters over food. While we lost him too soon, his legacy in the institute and in the field is cemented forever. Because Paul always dressed so formal and proper many people did not realize that he had a mischievous streak. When I joined the lab at Mount Sinai in 2007, I became the third Spanish postdoc in the lab (together with Andres Hidalgo and Simón Méndez-Ferrer). Paul spoke zero Spanish, but he had learned from Andres to pronounce the word “caramba”—which loosely translates as “Oh, this is surprising”—perfectly. For some reason he was inordinately proud of this and anytime that he talked with one of us he would start with an “Ah, caramba...” and continued using “caramba” through the conversation. For example, I might walk into his office and ask “Paul, can I show you some cool results?” He would reply, “Ah, caramba…Of course!” Then I’d go ahead and show him the data and—if the data were interesting and surprising enough—he would start saying “Caramba! Caramba!” excitedly. He’d then glance surreptitiously at me and start asking “Caramba? Caramba?” to see if I was confident with the results and would finish with a “Very good! Caramba!” I’d leave his office excited to know that my research was going in the right direction and proud of how cool my boss was. I am going to really miss running into him at a meeting and hearing “Ah! Caramba.” Paul was my mentor for more than nine years. During that time, he trained me as a scientist and became a cherished friend. His easy manner was disarming and even made interviewing for a coveted postdoc position in his lab a fond memory. I met Paul in Glasgow where he was giving a seminar on circadian regulation of the stem cell niche. Rather than meeting in a conference room, Paul suggested we go to a local pub to discuss science and watch the soccer World Cup. He could seamlessly ask astute questions, make suggestions on my PhD project, and make pointed comments on the game. The day after this meeting, Paul offered me a position in his lab that I quickly accepted, which has made all the difference in my life. Paul helped me and my lab colleagues (the “Frenettocytes”) grow tremendously as scientists (Figure 2). As I develop my own team now, I often ask myself, “What would Paul do?” Beyond science, Paul truly loved life with a massive passion for his family, friends, classical music, great wine, and good food. He had a wonderful boisterous laugh that would fill the room. I will miss him dearly." @default.
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