Jeffrey Flier is an American physician,

endocrinologist Endocrinology (from ''endocrine'' + '' -ology'') is a branch of biology and medicine dealing with the endocrine system, its diseases, and its specific secretions known as hormones. It is also concerned with the integration of developmental events ...

, widely cited scientist, ''Higginson Professor of Medicine and Physiology, and Harvard University Distinguished Service Professor'' at

Harvard Medical School Harvard Medical School (HMS) is the graduate medical school of Harvard University and is located in the Longwood Medical Area of Boston, Massachusetts. Founded in 1782, HMS is one of the oldest medical schools in the United States and is consi ...

. He was the 21st Dean of the Faculty of Medicine at

Harvard University Harvard University is a private Ivy League research university in Cambridge, Massachusetts. Founded in 1636 as Harvard College and named for its first benefactor, the Puritan clergyman John Harvard, it is the oldest institution of higher le ...

from 2007 to 2016.

Early life and career

Flier was born in

New York City New York, often called New York City or NYC, is the List of United States cities by population, most populous city in the United States. With a 2020 population of 8,804,190 distributed over , New York City is also the L ...

, and grew up in the

Pelham Parkway The Bronx and Pelham Parkway, also known formally as the Bronx–Pelham Parkway but called Pelham Parkway in everyday use, is a parkway in the borough of the Bronx in New York City. The road begins in Bronx Park at the Bronx River Parkway and U ...

section of the

Bronx The Bronx () is a borough of New York City, coextensive with Bronx County, in the state of New York. It is south of Westchester County; north and east of the New York City borough of Manhattan, across the Harlem River; and north of the New Y ...

. He is the son of Milton R. Flier, a

World War II World War II or the Second World War, often abbreviated as WWII or WW2, was a world war that lasted from 1939 to 1945. It involved the vast majority of the world's countries—including all of the great powers—forming two opposin ...

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 The Bronx High School of Science, commonly called Bronx Science, is a public specialized high school in The Bronx in New York City. It is operated by the New York City Department of Education. Admission to Bronx Science involves passing the Spec ...

, 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 The Icahn School of Medicine at Mount Sinai (ISMMS or Mount Sinai), formerly the Mount Sinai School of Medicine, is a private medical school in New York City. It is the academic teaching arm of the Mount Sinai Health System, which manages eigh ...

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 The National Institutes of Health, commonly referred to as NIH (with each letter pronounced individually), is the primary agency of the United States government responsible for biomedical and public health research. It was founded in the late ...

, completing training in endocrinology and launching a research career. He moved to

Boston Boston (), officially the City of Boston, is the state capital and most populous city of the Commonwealth of Massachusetts, as well as the cultural and financial center of the New England region of the United States. It is the 24th- mo ...

in 1978, becoming an assistant professor of medicine at

, 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 Beth Israel Deaconess Medical Center (BIDMC) in Boston, Massachusetts is a teaching hospital of Harvard Medical School. It was formed out of the 1996 merger of Beth Israel Hospital (founded in 1916) and New England Deaconess Hospital (founded ...

. 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 Carl Ronald Kahn (born January 14, 1944) is an American physician and scientist, best known for his work with insulin receptors and insulin resistance in diabetes and obesity. He is the Chief Academic Officer at Joslin Diabetes Center, the Mary K. ...

, 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 The insulin receptor (IR) is a transmembrane receptor that is activated by insulin, IGF-I, IGF-II and belongs to the large class of receptor tyrosine kinase. Metabolically, the insulin receptor plays a key role in the regulation of glucose homeo ...

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 Diabetes, also known as diabetes mellitus, is a group of metabolic disorders characterized by a high blood sugar level ( hyperglycemia) over a prolonged period of time. Symptoms often include frequent urination, increased thirst and increased ap ...

, advanced the field of

membrane receptor Cell surface receptors (membrane receptors, transmembrane receptors) are receptors that are embedded in the plasma membrane of cells. They act in cell signaling by receiving (binding to) extracellular molecules. They are specialized integral m ...

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

mutation In biology, a mutation is an alteration in the nucleic acid sequence of the genome of an organism, virus, or extrachromosomal DNA. Viral genomes contain either DNA or RNA. Mutations result from errors during DNA or viral replication, mi ...

s 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 ...

obesity Obesity is a medical condition, sometimes considered a disease, in which excess body fat has accumulated to such an extent that it may negatively affect health. People are classified as obese when their body mass index (BMI)—a person's we ...

; 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 Biology is the scientific study of life. It is a natural science with a broad scope but has several unifying themes that tie it together as a single, coherent field. For instance, all organisms are made up of cells that process hereditary i ...

and

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 Neuropeptides are chemical messengers made up of small chains of amino acids that are synthesized and released by neurons. Neuropeptides typically bind to G protein-coupled receptors (GPCRs) to modulate neural activity and other tissues like the ...

MCH in feeding behavior and energy balance; and the role of

FGF21 Fibroblast growth factor 21 is a liver-secreted peptide hormone that in humans is encoded by the ''FGF21'' gene. Together with FGF19 (FGF15 in rodents) and FGF23, this protein is a member of the endocrine subgroup within the fibroblast growth fa ...

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 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.

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. 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 The American Society for Clinical Investigation (ASCI), established in 1908, is one of the oldest and most respected medical honor societies in the United States. Organization and purpose The ASCI is an honorary society to which more than 2,800 ph ...

* 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 An International Standard Serial Number (ISSN) is an eight-digit serial number used to uniquely identify a serial publication, such as a magazine. The ISSN is especially helpful in distinguishing between serials with the same title. ISSNs ...

1078-8956.

PMID PubMed is a free search engine accessing primarily the MEDLINE database of references and abstracts on life sciences and biomedical topics. The United States National Library of Medicine (NLM) at the National Institutes of Health maintain the ...

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.

0028-0836.

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.

0036-8075.

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.

0021-9738. PMC 1616196.

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.

1932-7420.

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.

1549-5477. PMC 3278894.

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.

0092-8674.

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.

0066-4278.

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.

0021-9738. PMC 380258.

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.

0092-8674.

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.

0021-972X.

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.

0092-8674.

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.

1932-7420.

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.

2212-8778. PMC 5518722.

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.

2212-8778. PMC 5681240.

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.

2212-8778. PMC 6026320.

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.

1559-0100. PMC 7948212.

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.

1558-8238. PMC 7190986.

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.

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.

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.

1529-8795.

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.

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