The fields of stem cell research and hematology lost one of their brightest stars last week with the passing of Paul S. Frenette, M.D., who died on July 26 from angiosarcoma, a rare cancer. Dr. Frenette was 56.
A pioneer in hematopoietic stem cell research, Dr. Frenette was recruited in 2010 to become the founding director and chair of the Ruth L. and David S. Gottesman Institute for Stem Cell Biology and Regenerative Medicine Research at Albert Einstein College of Medicine. Also a professor of medicine and of cell biology, he made breakthrough observations that helped advance our understanding of vascular biology, sickle-cell disease, cancer, and stem cell biology.
Witty, light-hearted, focused, kind, and always genuine, Dr. Frenette was known for his passions for science, skiing, ice hockey, good food, and great wine. Above all, he adored his family and friends, and he loved life.
A cherished friend, mentor, co-worker, and brilliant collaborator, Dr. Frenette imparted ease, clarity, and joy no matter the setting or topic—whether it was a lively exchange at a scientific conference, discussing institutional issues in his office or lab in the Price Center, sharing a ride on the express bus from the Upper East Side to the Bronx, or pairing wines over dinner.
Dr. Frenette was a remarkably creative and productive scientist. A stem cell biologist, he found unique connections that had eluded others and employed highly sophisticated techniques to test his hypotheses. As a result, he was able to make a series of groundbreaking discoveries relating to the production and release of hematopoietic stem cells from their “niche” in the bone marrow; the mechanisms by which the abnormal red cells in sickle-cell anemia clump in blood vessels leading to sickle-cell crises; and the role of the autonomic nervous system in regulating the growth of prostate cancer and leukemia cells.
He established innovative imaging technologies to evaluate the significance of relationships between and within bone marrow niche structures. His keen understanding that dysregulation of some of the normal pathways could explain prostate cancer cell progression, sickle-cell vaso-occlusion, and normal aging led to conceptual breakthroughs on stem cell adhesion factors, nociceptive communication pathways, and circadian rhythms.
While Dr. Frenette was well known for his work in hematology and stem cell biology, his contributions to sickle-cell disease (SCD) were notable. He used sickle-cell mouse models to show that selectin-mediated leukocyte adhesion drives vascular occlusion. Those findings subsequently led to an anti-P-selectin antibody therapy for vaso-occlusion in patients with SCD. He also showed that intravenous immunoglobulin (IVIG), a treatment used in SCD, has a beneficial effect on vaso-occlusion in SCD.
Education and Early Career
A native of Canada, Dr. Frenette received his medical degree from Université Laval in Quebec City, followed by residency training at McGill University in Montreal; he completed a clinical fellowship in hematology-oncology at Tufts-New England Medical Center in Boston.
At Tufts, he met Johanna Daily, M.D., M.S., now an Einstein professor of medicine and an infectious diseases expert at Montefiore, who studies malaria. Dr. Daily remained a close friend and collaborator. She recalled that Dr. Frenette's first major scientific achievement occurred in Dr. Denisa Wagner's laboratory at the Center for Blood Research at Harvard Medical School, where he identified the critical roles of P and E selectin in the recruitment of white cells to areas of inflammation in 1996.
"This was the beginning of a storied career," Dr. Daily said, noting that Dr. Frenette inspired her work and generously provided expertise on a project that intersected malaria pathogenesis and vascular biology.
After a faculty appointment at Harvard Medical School, Dr. Frenette joined the faculty of Mount Sinai School of Medicine in 1998, rising from the rank of instructor to a tenured professor in 10 years.
An Outstanding Recruit
Allen Spiegel, M.D., Einstein’s dean emeritus, recalled recruiting Dr. Frenette to establish and run the Gottesman stem cell Institute in 2010.
"As I considered candidates to head the institute, I found Paul to be the most compelling, given the record of his accomplishments," said Dr. Spiegel, a professor of medicine and of molecular pharmacology. "Since coming to Einstein, his accomplishments reached an even higher level." Under Dr. Frenette's leadership, he added, the institute has grown to become a major research establishment.
Arthur Skoultchi, Ph.D., chair of the department of cell biology at Einstein, co-chaired the search committee that recommended Dr. Frenette. “In addition to Dr. Frenette’s enormous impact on a remarkably diverse set of important scientific and medical problems, the significance of his scientific contributions is apparent in the number of articles his lab published each year in the highest profile journals in the field of cell biology," Dr. Skoultchi said. "He had very high standards. His publications were extremely thorough. By his example, he raised the bar for all of us in the department of cell biology."
Yaron Tomer, M.D., chair of the department of medicine at Einstein and Montefiore, knew Dr. Frenette at both Mount Sinai and Einstein. "Paul was a brilliant scientist who made seminal discoveries, which not only unraveled new mechanisms underlying sickle-cell crises but have been translated into new innovative therapies. He will be sorely missed."
Gordon F. Tomaselli, M.D., the Marilyn and Stanley M. Katz Dean at Einstein and vice president and chief academic officer at Montefiore Medicine, echoed those sentiments: "Paul was a gifted scientist, wise mentor, exceptional leader, and an even better human being. He was taken from all of us too soon.”
An effective, engaging, and supportive leader, Dr. Frenette hired and mentored eight successful junior faculty members to grow the Gottesman Stem Cell Institute into the major research establishment it is today.
Keisuke Ito, M.D., Ph.D., was recruited by Dr. Frenette in 2012 from Harvard Medical School to become the institute’s director of scientific resources and to continue his research into hematopoietic and cancer stem cells.
"The day I learned Paul had slipped away from us was the saddest and probably the toughest day I have ever spent at Einstein," said Dr. Ito, who was among the first cohort of principal investigators to join the institute. One of Dr. Frenette’s great strengths as a scientist, he said, was his creativity, which enabled him to advance his research with remarkable innovation. In their meetings, Dr. Ito said he found it easy to discuss the challenges he faced running his lab and to seek advice from Dr. Frenette on his professional development. “He always offered sound advice, kept me on the right track, and helped me initiate and sustain a successful independent career here," Dr. Ito said.
A Creative Mentor
The Frenette laboratory provided an intellectual, innovative, and challenging space over the past 10 years for more than 20 funded trainees, most of whom who have gone on to academic careers. Dr. Frenette also mentored dozens of highly successful students and postdocs who are now flourishing in this country and around the world.
For Sandra Pinho, Ph.D., working under Dr. Frenette's guidance during her postdoctoral studies allowed her and her lab colleagues (the "Frenettocytes") to grow tremendously as scientists.
"As a mentor, Paul was extremely rigorous and very critical, two characteristics that really helped me change my way of thinking, and he guided me in asking the important scientific questions in the field," said Dr. Pinho, now an assistant professor of pharmacology at the University of Illinois at Chicago. "Now, as a junior faculty, I try to incorporate in my own style of mentorship the skills and passion for the work that I saw in Paul and wonder what his opinion about my new independent work would be."
She added, "Paul had a dry sense of humor, which contrasted with his big and loud laughter. As a trainee, I got used to losing bets with Paul, normally a beer that was never claimed. He loved to bet on some scientific result with his trainees, and 90% of the time, he was right!"
When Yoshio Katayama, M.D., Ph.D., joined the Frenette lab at Mount Sinai in 2000, he had little experience in bench science and publishing research. "Despite, my low profie, Paul allowed me to join his lab based on my original ideas and enthusiasm that he saw in my case reports," said Dr. Katayama, now a hematologist at Kobe University Hospital in Japan.
He noticed early on how Dr. Frenette recognized and nurtured the unique talent of each lab member. "Even if my idea was not the best, he always gave me a chance to try it until I could understand why it was good or bad. Now I manage my own lab in Japan and continue Paul's mentoring style with graduate students and postdocs," Dr. Katayama said, noting that one of his students, Dr. Noboru Asada, spent several years in Dr. Frenette’s Einstein lab as a postdoc. "Dr. Paul Frenette was a perfect educator. He loved people so much and, of course, people loved Paul."
Dr. Frenette was born in Quebec City. His father was an elementary school principal; his mother Ghislaine stayed home to raise her five children: Paul and his brothers Julien and Jerome and sisters Marie-Luce and Elise. At age 15, he was diagnosed with Hodgkin’s disease. His time spent in and out of the hospital for treatment fueled his motivation and passion for science.
Paul always enjoyed studying and working, which is why I think he pursued research and not medicine.
“Paul always enjoyed studying and working, which is why I think he pursued research and not medicine,” his wife, Nadine, observed. The couple met at a jazz club in Cambridge, Massachusetts, through a mutual friend in 1996. Dr. Frenette was a devoted father to their twins, Clara and Alberic.
His world view was that of a pacifist, said Ms. Frenette. An amateur enologist, he enjoyed visiting wineries and vineyards and meeting vintners. “Each summer, when we would visit my family in France, Paul would take his annual trip to Burgundy, a wine region in the northeast of France known for its pinot noir, where he would discuss winemaking for hours.” He also had a passion for music. “Paul LOVED classical music, especially Rachmaninoff, and often went to see the orchestras at the New York Philharmonic,” Ms. Frenette said.
Generous and Grateful Donors
Dr. Frenette's leadership at Einstein was made possible by Dr. Ruth and David Gottesman, whose generous philanthropy helped fund Einstein’s stem cell institute.
"Paul Frenette's untimely passing is a great loss to the Einstein community, not only because of his brilliant scientific research but also because of his exemplary human qualities of kindness, thoughtfulness, and respect of others," said Dr. Gottesman, chair of Einstein's Board of Trustees. "My husband and I were strong supporters of Paul's work, not only because of the quality of his research, but also his outstanding qualities as person. We will miss him tremendously."
Editor's Note: If you would like to leave a remembrance of Dr. Frenette, please visit our Leave a Remembrance Page.
For those who wish to make a contribution in Paul's name, his family is establishing a fund in his memory at Einstein.
Posted on: Friday, August 06, 2021