Jeffrey S. Flier
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Jeffrey Flier is an American physician, endocrinologist, widely cited scientist, ''Higginson Professor of Medicine and Physiology, and Harvard University Distinguished Service Professor'' at Harvard Medical School. He was the 21st Dean of the Faculty of Medicine at Harvard University from 2007 to 2016.


Early life and career

Flier was born in New York City, and grew up in the Pelham Parkway section of the Bronx. He is the son of Milton R. Flier, a World War II
C-47 The Douglas C-47 Skytrain or Dakota (Royal Air Force, RAF, Royal Australian Air Force, RAAF, Royal Canadian Air Force, RCAF, Royal New Zealand Air Force, RNZAF, and South African Air Force, SAAF designation) is a airlift, military transport ai ...
pilot and businessperson, and Dorothy (Kroll) Flier, who taught junior high school mathematics. He graduated in 1964 from the Bronx High School of Science, and 1968 from the
City College of New York The City College of the City University of New York (also known as the City College of New York, or simply City College or CCNY) is a public university within the City University of New York (CUNY) system in New York City. Founded in 1847, Cit ...
. He was in the first entering class of the Mount Sinai School of Medicine in 1968, and graduated in 1972 with the Elster Prize for highest academic standing.An opponent to healthcare for all. After two years of internal medicine residency at Mount Sinai Hospital, he spent four years in the Public Health Service as a clinical associate at the National Institutes of Health, completing training in endocrinology and launching a research career. He moved to Boston in 1978, becoming an assistant professor of medicine at Harvard Medical School, and chief of the Diabetes Unit at Harvard-affiliated Beth Israel Hospital. He subsequently became chief of the hospital's Endocrinology Division, vice chair for research of the Department of Medicine, and eventually the hospital's chief academic officer in 2002, overseeing research and educational affairs. At Harvard Medical School, he became the George C. Reisman Professor of Medicine, and Harvard faculty dean for Academic Affairs at what became the Beth Israel Deaconess Medical Center. At BIDMC he served as a Chief Academic Officer from 2002 to 2007.


Appointment as Dean of Harvard's Faculty of Medicine

Flier was appointed Dean of the Faculty of Medicine and the Caroline Shields Walker professor of medicine at Harvard in July 2007 by President Drew Faust and assumed the position on September 1, 2007. During his first year as dean, he led an extensive strategic planning process, releasing a report in October 2008. Harvard University and Harvard Medical School suffered financial losses when financial markets fell in 2008–2009. This slowed but did not stop investments in several areas. His term as dean of Harvard Medical School ended in 2016 after nine years. Some of the corporate accomplishments corresponding to his period as a Dean were: 1. implementation of a new Clinical and Translational Science Award from NIH; 2. successful launch and oversight of the $750 million “The World is Waiting” capital campaign; 3. implementation of a major redesign of the preclinical medical curriculum; 4. design and implementation of a new system for financial contributions to HMS from its affiliated institutions; 5. establishment of a new department of biomedical informatics; 6. establishment of a new division of external education, combining Harvard Health Publishing, postgraduate medical education, and new HMS online learning and executive education programs designed to increase the global impact and educational revenues of the institution. Flier's 2016 final class commencement speech at Harvard Medical School is available online.


Research contributions

While at the Diabetes Branch of NIH, under the mentorship of
Jesse Roth Jesse Roth (born August 5, 1934) is an American physician and endocrinologist, currently at The Feinstein Institute for Medical Research. He received his BA in 1955 from Columbia University, his MD in 1959 from Albert Einstein College of Medicine. ...
, Philip Gorden, and C. Ronald Kahn, Flier discovered the existence of
autoantibodies An autoantibody is an antibody (a type of protein) produced by the immune system that is directed against one or more of the individual's own proteins. Many autoimmune diseases (notably lupus erythematosus) are associated with such antibodies. Pr ...
to the insulin receptor as a cause of severe
insulin resistance Insulin resistance (IR) is a pathological condition in which cell (biology), cells fail to respond normally to the hormone insulin. Insulin is a hormone that facilitates the transport of glucose from blood into cells, thereby reducing blood gluco ...
. This discovery elucidated a rare cause of diabetes, advanced the field of membrane receptor biology and provided an important tool for research on insulin action. Flier also played a major role in defining genetic causes of insulin resistance by identifying and characterizing mutations in the insulin receptor gene in a subset of patients with severe insulin resistance. Much of his research has addressed the
pathophysiology Pathophysiology ( physiopathology) – a convergence of pathology with physiology – is the study of the disordered physiological processes that cause, result from, or are otherwise associated with a disease or injury. Pathology is the ...
of obesity; In 1993, he described the dynamics of obesity in a brown-fat defficient, transgenic mouse model; His most extensive work has related to the biology and
pathophysiology Pathophysiology ( physiopathology) – a convergence of pathology with physiology – is the study of the disordered physiological processes that cause, result from, or are otherwise associated with a disease or injury. Pathology is the ...
of
leptin Leptin (from Ancient Greek, Greek λεπτός ''leptos'', "thin" or "light" or "small") is a hormone predominantly made by adipose cells and enterocytes in the small intestine that helps to regulate Energy homeostasis, energy balance by inhib ...
, its physiological role in
starvation Starvation is a severe deficiency in caloric energy intake, below the level needed to maintain an organism's life. It is the most extreme form of malnutrition. In humans, prolonged starvation can cause permanent organ damage and eventually, dea ...
, and the molecular mechanisms of leptin resistance in obesity. With Maratos-Flier, he studied the participation of neuropeptide MCH in feeding behavior and energy balance; and the role of FGF21 in
metabolic Metabolism (, from el, μεταβολή ''metabolē'', "change") is the set of life-sustaining chemical reactions in organisms. The three main functions of metabolism are: the conversion of the energy in food to energy available to run cell ...
regulation. With Bruce Spiegelman he discovered an altered production of
adipsin Factor D (, ''C3 proactivator convertase'', ''properdin factor D esterase'', ''factor D (complement)'', ''complement factor D'', ''CFD'', ''adipsin'') is a protein which in humans is encoded by the ''CFD'' gene. Factor D is involved in the alterna ...
in obesity in genetically obese mice. In 2005, he reported the possible role of adult
hypothalamic The hypothalamus () is a part of the brain that contains a number of small nuclei with a variety of functions. One of the most important functions is to link the nervous system to the endocrine system via the pituitary gland. The hypothalamus i ...
neurogenesis Neurogenesis is the process by which nervous system cells, the neurons, are produced by neural stem cells (NSCs). It occurs in all species of animals except the porifera (sponges) and placozoans. Types of NSCs include neuroepithelial cells (NECs) ...
in the control of energy balance; Regarding inflammatory phenomena in metabolic disease, Flier helped establish that Toll-like receptor 4 (TLR4) activation in adipocytes and macrophages mediates inflammation accompanying obesity, and subsequent insulin resistance in diabetes. In 1980 he described a rare case of familial
acanthosis nigricans-muscle cramps-acral enlargement syndrome Acanthosis nigricans-muscle cramps-acral enlargement syndrome, also known as Acanthosis nigricans-insulin resistance-muscle cramps-acral enlargement syndrome is an extremely rare genetic disorder which is characterized by the appearance of acan ...
.


Opinion

Since stepping down as dean, Flier has increasingly contributed  policy oriented  publications focusing on a number of issues affecting health care and biomedical research in current times, among them: health care reform and its sustainability, enhancing US health provider workforce, the pros and cons of prevailing credit attribution practices in academia and industry, the realities and options linked to the irreproducibility of research results, improving the institutional handling of scientific misconduct, the obsolescence of distinctions between basic and translational biomedical research, and the complexities behind conflict of interest (COI) disclosure.


Personal life

Flier is married to
Eleftheria Maratos-Flier Eleftheria Maratos-Flier is an American endocrinologist, and emerita Professor of Medicine at Harvard Medical School, best known for her expertise in the pathophysiology and prevention of obesity-related metabolic disorders, and for her discoveries ...
. She is an endocrinologist and Professor of Medicine at Harvard Medical School, and currently a director of clinical research at Alynylam Pharmaceuticals. The two have collaborated in several areas of research. They have two daughters. Sarah and Lydia, both of whom are physicians.


Honors/affiliations/awards

* Institute of Medicine of the National Academies of Science * American Academy of Arts and Sciences * American Society for Clinical Investigation * Association of American Physicians * Eli Lilly Award, American Diabetes Association * Banting Medal, American Diabetes Association * Solomon Berson Lecture, American Physiological Society * Albert Renold Award, American Diabetes Association * Astwood Lecture, Endocrine Society * Honorary Doctor of Science, University of Athens * Doctor of Science, Honoris Causa, University of Edinburgh * Advisory Council, National Institutes of Diabetes and Digestive and Kidney Diseases, NIH


Selected works


Biomedical Research

Flier has published over 350 research papers papers and subject reviews, which have been jointly cited over 110.000 times, his overall h-index is 150.


Most cited original research

His most cited original research papers are: * Frederich, R. C.; Hamann, A.; Anderson, S.; Löllmann, B.; Lowell, B. B.; Flier, J. S. (1995-12). "Leptin levels reflect body lipid content in mice: evidence for diet-induced resistance to leptin action". ''Nature Medicine''. 1 (12): 1311–1314. doi:10.1038/nm1295-1311. ISSN 1078-8956. PMID 7489415. Cited 1998 times, June 2022 * Ahima, R. S.; Prabakaran, D.; Mantzoros, C.; Qu, D.; Lowell, B.; Maratos-Flier, E.; Flier, J. S. (1996-07-18). "Role of leptin in the neuroendocrine response to fasting". ''Nature''. 382 (6588): 250–252. doi:10.1038/382250a0. ISSN 0028-0836. PMID 8717038. Cited 3870 times, June 2022 * Masuzaki, H.; Paterson, J.; Shinyama, H.; Morton, N. M.; Mullins, J. J.; Seckl, J. R.; Flier, J. S. (2001-12-07). "A transgenic model of visceral obesity and the metabolic syndrome". ''Science''. 294 (5549): 2166–2170. doi:10.1126/science.1066285. ISSN 0036-8075. PMID 11739957. Cited 227 times, June 2022 *Shi, Hang; Kokoeva, Maia V.; Inouye, Karen; Tzameli, Iphigenia; Yin, Huali; Flier, Jeffrey S. (2006–11). "TLR4 links innate immunity and fatty acid-induced insulin resistance". ''The Journal of Clinical Investigation''. 116 (11): 3015–3025. doi:10.1172/JCI28898. ISSN 0021-9738. PMC 1616196. PMID 17053832. Cited 3854 times, June 2022 *Badman, Michael K.; Pissios, Pavlos; Kennedy, Adam R.; Koukos, George; Flier, Jeffrey S.; Maratos-Flier, Eleftheria (2007-06). "Hepatic fibroblast growth factor 21 is regulated by PPARalpha and is a key mediator of hepatic lipid metabolism in ketotic states". ''Cell Metabolism''. 5 (6): 426–437. doi:10.1016/j.cmet.2007.05.002. ISSN 1932-7420. PMID 17550778. Cited 1516 times, June 2022 *Fisher, Ffolliott M.; Kleiner, Sandra; Douris, Nicholas; Fox, Elliott C.; Mepani, Rina J.; Verdeguer, Francisco; Wu, Jun; Kharitonenkov, Alexei; Flier, Jeffrey S.; Maratos-Flier, Eleftheria; Spiegelman, Bruce M. (2012-02-01). "FGF21 regulates PGC-1α and browning of white adipose tissues in adaptive thermogenesis". ''Genes & Development''. 26 (3): 271–281. doi:10.1101/gad.177857.111. ISSN 1549-5477. PMC 3278894. PMID 22302939. Cited 1373 times, June 2022


Most cited subject reviews

* Spiegelman, B. M.; Flier, J. S. (1996-11-01). "Adipogenesis and obesity: rounding out the big picture". ''Cell''. 87 (3): 377–389. doi:10.1016/s0092-8674(00)81359-8. ISSN 0092-8674. PMID 8898192. Cited 1615 times, June 2022 * Ahima, R. S.; Flier, J. S. (2000). "Leptin". ''Annual Review of Physiology''. 62: 413–437. doi:10.1146/annurev.physiol.62.1.413. ISSN 0066-4278. PMID 10845097. Cited 2606 times, June 2022 * Kahn, Barbara B.; Flier, Jeffrey S. (2000-08-15). "Obesity and insulin resistance". ''Journal of Clinical Investigation''. 106 (4): 473–481. doi:10.1172/JCI10842. ISSN 0021-9738. PMC 380258. PMID 10953022. Cited 4115 times, June 2022 * Spiegelman, B. M.; Flier, J. S. (2001-02-23). "Obesity and the regulation of energy balance". ''Cell''. 104 (4): 531–543. doi:10.1016/s0092-8674(01)00240-9. ISSN 0092-8674. PMID 11239410. Cited 2993 times, June 2022 * Kershaw, Erin E.; Flier, Jeffrey S. (2004–06). "Adipose tissue as an endocrine organ". ''The Journal of Clinical Endocrinology and Metabolism''. 89 (6): 2548–2556. doi:10.1210/jc.2004-0395. ISSN 0021-972X. PMID 15181022. Cited 6496 times, June 2022 *Flier, Jeffrey S. (2004-01-23). "Obesity wars: molecular progress confronts an expanding epidemic". ''Cell''. 116 (2): 337–350. doi:10.1016/s0092-8674(03)01081-x. ISSN 0092-8674. PMID 14744442. Cited 1589 times, June 2022.


Most recent biomedical papers

* Flier, Jeffrey S.; Maratos-Flier, Eleftheria (2017-07-05). "Leptin's Physiologic Role: Does the Emperor of Energy Balance Have No Clothes?". ''Cell Metabolism''. 26 (1): 24–26. doi:10.1016/j.cmet.2017.05.013. ISSN 1932-7420. PMID 28648981 * Douris, Nicholas; Desai, Bhavna N.; Fisher, Ffolliott M.; Cisu, Theodore; Fowler, Alan J.; Zarebidaki, Eleen; Nguyen, Ngoc Ly T.; Morgan, Donald A.; Bartness, Timothy J.; Rahmouni, Kamal; Flier, Jeffrey S. (2017-08). "Beta-adrenergic receptors are critical for weight loss but not for other metabolic adaptations to the consumption of a ketogenic diet in male mice". ''Molecular Metabolism''. 6 (8): 854–862. doi:10.1016/j.molmet.2017.05.017. ISSN 2212-8778. PMC 5518722. PMID 28752049 * Desai, Bhavna N.; Singhal, Garima; Watanabe, Mikiko; Stevanovic, Darko; Lundasen, Thomas; Fisher, Ffolliott M.; Mather, Marie L.; Vardeh, Hilde G.; Douris, Nicholas; Adams, Andrew C.; Nasser, Imad A. (2017-11). "Fibroblast growth factor 21 (FGF21) is robustly induced by ethanol and has a protective role in ethanol associated liver injury". ''Molecular Metabolism''. 6 (11): 1395–1406. doi:10.1016/j.molmet.2017.08.004. ISSN 2212-8778. PMC 5681240. PMID 29107287 * Singhal, Garima; Kumar, Gaurav; Chan, Suzanne; Fisher, Ffolliott M.; Ma, Yong; Vardeh, Hilde G.; Nasser, Imad A.; Flier, Jeffrey S.; Maratos-Flier, Eleftheria (2018-07). "Deficiency of fibroblast growth factor 21 (FGF21) promotes hepatocellular carcinoma (HCC) in mice on a long term obesogenic diet". ''Molecular Metabolism''. 13: 56–66. doi:10.1016/j.molmet.2018.03.002. ISSN 2212-8778. PMC 6026320. PMID 29753678 * Watanabe, Mikiko; Singhal, Garima; Fisher, Ffolliott M.; Beck, Thomas C.; Morgan, Donald A.; Socciarelli, Fabio; Mather, Marie L.; Risi, Renata; Bourke, Jared; Rahmouni, Kamal; McGuinness, Owen P. (2020-01). "Liver-derived FGF21 is essential for full adaptation to ketogenic diet but does not regulate glucose homeostasis". ''Endocrine''. 67 (1): 95–108. doi:10.1007/s12020-019-02124-3. ISSN 1559-0100. PMC 7948212. PMID 31728756 * Flier, Jeffrey S. (2020-05-01). "Might β3-adrenergic receptor agonists be useful in disorders of glucose homeostasis?". ''The Journal of Clinical Investigation''. 130 (5): 2180–2182. doi:10.1172/JCI136476. ISSN 1558-8238. PMC 7190986. PMID 32202511


Recent policy papers

* Flier, Jeffrey S. (2019). "Credit and Priority in Scientific Discovery: A Scientist's Perspective". ''Perspectives in Biology and Medicine''. 62 (2): 189–215. doi:10.1353/pbm.2019.0010. ISSN 1529-8795 * Flier, Jeffrey S. (2019-06-03). "Academia and industry: allocating credit for discovery and development of new therapies". ''The Journal of Clinical Investigation''. 129 (6): 2172–2174. doi:10.1172/JCI129122. ISSN 0021-9738 *Flier, Jeffrey S.; Rhoads, Jared M. (2020). "The US Health Provider Workforce: Determinants and Potential Paths to Enhancement". ''Perspectives in Biology and Medicine''. 63 (4): 644–668. doi:10.1353/pbm.2020.0053. ISSN 1529-8795. PMID 33416803 *Flier, Jeffrey S. (2021). "Misconduct in Bioscience Research: a 40-year perspective". ''Perspectives in Biology and Medicine''. 64 (4): 437–456. doi:10.1353/pbm.2021.0035. ISSN 1529-8795


Notes


References


External links


Dean of the Faculty of Medicine

Dr. Flier's Welcome Address to the Class of 2016

Dr Flier's interview about his life and career with Vinay Prasad, 2021
{{DEFAULTSORT:Flier, Jeffrey Scott 1948 births Living people American endocrinologists Icahn School of Medicine at Mount Sinai alumni The Bronx High School of Science alumni Harvard Medical School faculty City College of New York alumni Members of the National Academy of Medicine