Jeffrey Scott Flier

Last updated
Jeffrey Scott Flier
21st Dean of the Harvard Medical School
In office
September 1, 2007 –July 31, 2016
Personal details
Born (1948-02-27) February 27, 1948 (age 70)
New York, New York
Spouse(s) Eleftheria Maratos-Flier
Children Sarah Flier and Lydia Flier
Website Dean of the Faculty of Medicine

Jeffrey Scott Flier (born February 27, 1948) is an American physician, endocrinologist, researcher, and the 21st Dean of the Faculty of Medicine at Harvard University. [1]

Endocrinology medical specialty

Endocrinology 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 proliferation, growth, and differentiation, and the psychological or behavioral activities of metabolism, growth and development, tissue function, sleep, digestion, respiration, excretion, mood, stress, lactation, movement, reproduction, and sensory perception caused by hormones. Specializations include behavioral endocrinology and comparative endocrinology.

Harvard University private research university in Cambridge, Massachusetts, United States

Harvard University is a private Ivy League research university in Cambridge, Massachusetts, with about 6,700 undergraduate students and about 15,250 postgraduate students. Established in 1636 and named for its first benefactor, clergyman John Harvard, Harvard is the United States' oldest institution of higher learning, and its history, influence, and wealth have made it one of the world's most prestigious universities.

Contents

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 pilot and businessperson, and Dorothy 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. 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. [1] 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 HMS, 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. [2]

New York City Largest city in the United States

The City of New York, usually called either New York City (NYC) or simply New York (NY), is the most populous city in the United States. With an estimated 2017 population of 8,622,698 distributed over a land area of about 302.6 square miles (784 km2), New York is also the most densely populated major city in the United States. Located at the southern tip of the state of New York, the city is the center of the New York metropolitan area, the largest metropolitan area in the world by urban landmass and one of the world's most populous megacities, with an estimated 20,320,876 people in its 2017 Metropolitan Statistical Area and 23,876,155 residents in its Combined Statistical Area. A global power city, New York City has been described as the cultural, financial, and media capital of the world, and exerts a significant impact upon commerce, entertainment, research, technology, education, politics, tourism, art, fashion, and sports. The city's fast pace has inspired the term New York minute. Home to the headquarters of the United Nations, New York is an important center for international diplomacy.

Pelham Parkway (neighborhood), Bronx Neighborhood of the Bronx in New York City

Pelham Parkway is a working- and middle-class residential neighborhood geographically located in the center of the Bronx, a borough of New York City in the United States. The neighborhood is part of Bronx Community Board 11. Its boundaries, starting from the north and moving clockwise are: Waring Avenue to the north, the IRT Dyre Avenue Line tracks to the east, Neill Avenue to the South, and Bronx River Parkway to the west. White Plains Road is the primary commercial thoroughfare through Pelham Parkway. Additionally, Pelham Parkway is a major parkway in the neighborhood, which gives way to the neighborhood's name.

World War II 1939–1945 global war

World War II, also known as the Second World War, was a global war that lasted from 1939 to 1945. The vast majority of the world's countries—including all the great powers—eventually formed two opposing military alliances: the Allies and the Axis. A state of total war emerged, directly involving more than 100 million people from over 30 countries. The major participants threw their entire economic, industrial, and scientific capabilities behind the war effort, blurring the distinction between civilian and military resources. World War II was the deadliest conflict in human history, marked by 50 to 85 million fatalities, most of whom were civilians in the Soviet Union and China. It included massacres, the genocide of the Holocaust, strategic bombing, premeditated death from starvation and disease, and the only use of nuclear weapons in war.

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. [2] During his first year as dean, he led an extensive strategic planning process, releasing a report in October 2008. [3] Harvard University and Harvard Medical School suffered financial losses when markets fell in 2008-9. This slowed but did not stop investments in several areas. [4] Notably Flier penned an op-ed as Dean of Harvard Medical School opposing expansion of health insurance in the United States. [5] His term as dean of Harvard Medical School ended in 2016 after nine years. [6]

Research contributions

Flier has contributed to many areas in metabolism research over 35 years at NIH and Harvard. While at the Diabetes Branch of NIH, under the mentorship of Jesse Roth, MD, FACP, Philip Gorden, MD, and C. Ronald Kahn, MD, he discovered the existence of autoantibodies to the insulin receptor as a cause of severe insulin resistance. [7] This discovery elucidated a rare cause of diabetes, [8] advanced the field of membrane receptor biology and provided an important tool for research on insulin action. [9] 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. [10] [11] Much of his research has addressed the pathophysiology of obesity. [12] [13] [14] Among his work has been the discovery with Bruce Spiegelman, PhD, of altered production of adipocyte secreted factors in obesity; [15] investigations into the function of brown adipose tissue through creation of a brown fat deficient transgenic mouse; [16] elucidation of the role of the neuropeptide MCH in energy balance by making an MCH knockout mouse (with his wife, Eleftheria Maratos-Flier, MD); [17] identification of the capacity of adult hypothalamic neurogenesis to occur and influence energy balance; [18] and work with Maratos-Flier to define the role of FGF21 in metabolic regulation. [19] His most extensive work has related to the biology and pathophysiology of leptin. His lab has defined the role of leptin as a key molecule in the physiology of starvation, [20] and has provided evidence for the molecular mechanism of leptin resistance that characterizes and contributes to obesity. [21]

C. Ronald Kahn American physician

Carl Ronald Kahn 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. Iacocca Professor of Medicine at Harvard Medical School and a member of the National Academy of Sciences since 1999.

An autoantibody is an antibody produced by the immune system that is directed against one or more of the individual's own proteins. Many autoimmune diseases are caused by such autoantibodies.

Insulin receptor protein-coding gene in the species Homo sapiens

The insulin receptor (IR) is a transmembrane receptor that is activated by insulin, IGF-I, IGF-II and belongs to the large class of tyrosine kinase receptors. Metabolically, the insulin receptor plays a key role in the regulation of glucose homeostasis, a functional process that under degenerate conditions may result in a range of clinical manifestations including diabetes and cancer. Insulin signalling controls access to blood glucose in body cells. When insulin falls, especially in those with high insulin sensitivity, body cells begin only to have access to lipids that do not require transport across the membrane. So, in this way, insulin is the key regulator of fat metabolism as well. Biochemically, the insulin receptor is encoded by a single gene INSR, from which alternate splicing during transcription results in either IR-A or IR-B isoforms. Downstream post-translational events of either isoform result in the formation of a proteolytically cleaved α and β subunit, which upon combination are ultimately capable of homo or hetero-dimerisation to produce the ≈320 kDa disulfide-linked transmembrane insulin receptor.

Personal life

Flier is married to Eleftheria Maratos-Flier. She is an endocrinologist and Professor of Medicine at Harvard Medical School, [22] and the two have collaborated in several areas of research. [17] [12] [14] They have two daughters. Sarah Flier, MD, is a gastroenterologist at Beth Israel Deaconess Medical Center, and an instructor in Medicine at Harvard Medical School. [23] Lydia Flier is a third year student at Harvard Medical School. His brother Steven Flier, MD, is a Harvard-affiliated internist practicing in Chestnut Hill, Massachusetts. [24]

Honors/affiliations/awards

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.

Selected works

Biomedical Research
Policy

Notes

Related Research Articles

Insulin resistance (IR) is considered as a pathological condition in which cells fail to respond normally to the hormone insulin. To prevent hyperglycemia and noticeable organ damage over time, the body produces insulin when glucose starts to be released into the bloodstream, primarily from the digestion of carbohydrates in the diet. Under normal conditions of insulin reactivity, this insulin response triggers glucose being taken into body cells, to be used for energy, and inhibits the body from using fat for energy, thereby causing the concentration of glucose in the blood to decrease as a result, staying within the normal range even when a large amount of carbohydrates is consumed. Carbohydrates comprise simple sugars, i.e. monosaccharides, such as glucose and fructose, disaccharides, such as cane sugar, and polysaccharides, e.g. starches. Fructose, which is metabolised into triglycerides in the liver, stimulates insulin production through another mechanism, and can have a more potent effect than other carbohydrates. A habitually high intake of carbohydrates, and particularly fructose, e.g. with sweetened beverages, contributes to insulin resistance and has been linked to weight gain and obesity. If excess blood sugar is not sufficiently absorbed by cells even in the presence of insulin, the increase in the level of blood sugar can result in the classic hyperglycemic triad of polyphagia, polydipsia, and polyuria. Avoiding carbohydrates and sugars, a no-carbohydrate diet or fasting can reverse insulin resistance.

Leptin protein-coding gene in the species Homo sapiens

Leptin is a hormone predominantly made by adipose cells that helps to regulate energy balance by inhibiting hunger. This hormone acts on receptors in the arcuate nucleus of the hypothalamus. In obesity, a decreased sensitivity to leptin occurs, resulting in an inability to detect satiety despite high energy stores and high levels of leptin.

In biology, adipose tissue, body fat, or simply fat is a loose connective tissue composed mostly of adipocytes. In addition to adipocytes, adipose tissue contains the stromal vascular fraction (SVF) of cells including preadipocytes, fibroblasts, vascular endothelial cells and a variety of immune cells such as adipose tissue macrophages. Adipose tissue is derived from preadipocytes. Its main role is to store energy in the form of lipids, although it also cushions and insulates the body. Far from being hormonally inert, adipose tissue has, in recent years, been recognized as a major endocrine organ, as it produces hormones such as leptin, estrogen, resistin, and the cytokine TNFα. The two types of adipose tissue are white adipose tissue (WAT), which stores energy, and brown adipose tissue (BAT), which generates body heat. The formation of adipose tissue appears to be controlled in part by the adipose gene. Adipose tissue – more specifically brown adipose tissue – was first identified by the Swiss naturalist Conrad Gessner in 1551.

Adipocyte cells that primarily compose adipose tissue, specialized in storing energy as fat

Adipocytes, also known as lipocytes and fat cells, are the cells that primarily compose adipose tissue, specialized in storing energy as fat. Adipocytes are derived from mesenchymal stem cells which give rise to adipocytes, osteoblasts, myocytes and other cell types through adipogenesis.

Adiponectin protein-coding gene in the species Homo sapiens

Adiponectin is a protein hormone which is involved in regulating glucose levels as well as fatty acid breakdown. In humans it is encoded by the ADIPOQ gene and it is produced in adipose tissue.

Resistin protein-coding gene in the species Homo sapiens

Resistin also known as adipose tissue-specific secretory factor (ADSF) or C/EBP-epsilon-regulated myeloid-specific secreted cysteine-rich protein (XCP1) is a cysteine-rich adipose-derived peptide hormone that in humans is encoded by the RETN gene.

Hyperinsulinemia condition in which there are excess levels of insulin circulating in the blood relative to the level of glucose

Hyperinsulinemia, is a condition in which there are excess levels of insulin circulating in the blood relative to the level of glucose. While it is often mistaken for diabetes or hyperglycaemia, hyperinsulinemia can result from a variety of metabolic diseases and conditions. While hyperinsulinemia is often seen in people with early stage type 2 diabetes mellitus, it is not the cause of the condition and is only one symptom of the disease. Type 1 diabetes only occurs when pancreatic beta-cell function is impaired. Hyperinsulinemia can be seen in a variety of conditions including diabetes mellitus type 2, in neonates and in drug induced hyperinsulinemia. It can also occur in congenital hyperinsulism, including nesidioblastosis.

Jeffrey M. Friedman Physician scientist studying the genetic mechanisms that regulate body weight.

Jeffrey M. Friedman is a molecular geneticist at New York City's Rockefeller University and an Investigator of the Howard Hughes Medical Institute. His discovery of the hormone leptin and its role in regulating body weight has had a major role in the area of human obesity. Friedman is a physician scientist studying the genetic mechanisms that regulate body weight. His research on various aspects of obesity received national attention in late 1994, when it was announced that he and his colleagues had isolated the mouse ob gene and its human homologue. They subsequently found that injections of the encoded protein, leptin, decreases body weight of mice by reducing food intake and increasing energy expenditure. Current research is aimed at understanding the genetic basis of obesity in human and the mechanisms by which leptin transmits its weight-reducing signal.

Leukotriene B4 (LTB4) is a leukotriene involved in inflammation. It has been shown to promote insulin resistance in obese mice.

Leptin receptor protein-coding gene in the species Homo sapiens

Leptin receptor also known as LEP-R or OB-R is a Type I cytokine receptor, a protein that in humans is encoded by the LEPR gene. LEP-R functions as a receptor for the fat cell-specific hormone leptin. LEP-R has also been designated as CD295. Its location is the cell membrane, and it has extracellular, trans-membrane, and intracellular sections.

ob/ob mouse mutant mouse that eats excessively and becomes profoundly obese

The ob/ob or obese mouse is a mutant mouse that eats excessively due to mutations in the gene responsible for the production of leptin and becomes profoundly obese. It is an animal model of type II diabetes. Identification of the gene mutated in ob led to the discovery of the hormone leptin, which is important in the control of appetite.

Adipose tissue is an endocrine organ that secretes numerous protein hormones, including leptin, adiponectin, and resistin. These hormones generally influence energy metabolism, which is of great interest to the understanding and treatment of type 2 diabetes and obesity.

Douglas L. Coleman was a scientist and professor at The Jackson Laboratory, in Bar Harbor, Maine. His work predicted that the ob gene encoded the hormone leptin, later co-discovered in 1994 by Jeffrey Friedman, Rudolph Leibel and their research teams at Rockefeller University. This work has had a major role in our understanding of the mechanisms regulating body weight and that cause of human obesity.

Adipotide, a peptidomimetic with sequence CKGGRAKDC-GG-D(KLAKLAK)2, is an experimental proapoptotic drug that has been shown to cause rapid weight loss in mice and rhesus monkeys. Its mechanism of action is to target specific blood vessels supplying adipose tissue with blood, cause the vessels to shrink and the fat cells fed by those vessels to undergo apoptosis. Adipotide is designed to bind to two receptors, ANXA2 and prohibitin, that are specific to blood vessels supplying white adipose tissue.

Rudolph Leibel American medical researcher

Rudolph Leibel is the Christopher J. Murphy Professor of Diabetes Research, Professor of Pediatrics and Medicine at Columbia University Medical Center, and Director of the Division of Molecular Genetics in the Department of Pediatrics. He is also Co-Director of the Naomi Berrie Diabetes Center and Executive Director of the Russell and Angelica Berrie Program in Cellular Therapy, Co-Director of the New York Obesity Research Center and the Columbia University Diabetes and Endocrinology Research Center.

Jose F. Caro American physician

José F. Caro, M.D. is an American physician, scientist, and educator most notable for his research in obesity and diabetes. The Institute for Scientific Information listed him the third most cited investigator in the world in the field of obesity research during the 1991-2000 period for his work on Leptin. Caro is also an artist.

AdipoRon chemical compound

AdipoRon is a selective, orally active, synthetic small-molecule agonist of the adiponectin receptor 1 (AdipoR1) and adiponectin receptor 2 (AdipoR2). It activates AMPK and PPARα signaling and ameliorates insulin resistance, dyslipidemia, and glucose intolerance in db/db mice. Moreover, AdipoRon has been found to extend the lifespans of db/db mice fed a high-fat diet, as well as improve exercise endurance. The compound was discovered by Japanese researchers in 2013 via screening of a compound library, and is the first orally active, small-molecule agonist of the adiponectin receptors to be identified.

Christos Socrates Mantzoros

Christos Socrates Mantzoros is a Greek American physician scientist, internist - endocrinologist, researcher, Harvard Medical School professor and the editor-in-chief of the journal Metabolism: Clinical and Experimental. He is considered a pioneer and worldwide expert in obesity and metabolism. He has given more than 500 lectures nationally and internationally on these critical topics. His research has resulted in more than 800 publications in Medline, including more than 150 publications under the collaborative Look Ahead Research Group, more than 200 chapters and reviews and has received more than 72,000 citations with an h-index=121 as well as prestigious awards at national and international meetings. He has an H index of 114.

(Ismaa) Sadaf Farooqi FMedSci is a Wellcome Trust Senior Research fellow in Clinical Science, professor of Metabolism and Medicine at the University of Cambridge and a consultant physician at Addenbrooke's Hospital in Cambridge, UK.

References

  1. 1 2 3 4 5 6 7 8 9 An opponent to healthcare for all. "Jeffrey S. Flier, MD, Dean of Harvard Medical School".
  2. 1 2 3 4 "Jeffrey S. Flier named next dean of Faculty of Medicine". Harvard Gazette. 11 July 2007.
  3. ↑ "Strategic Planning at Harvard Medical School" (PDF). October 2008.
  4. ↑ "The Dean's Report 2008-2009" (PDF). 2008.
  5. ↑ Flier, Jeffrey. "Health 'Reform' Gets a Failing Grade". Wall Street Journal. Retrieved 16 August 2012.
  6. ↑ Flier, Jeffrey. "New Dean for Faculty of Medicine". Harvard Medical School. Retrieved 9 August 2016.
  7. ↑ Flier, JS; Kahn, CR; Roth, J; Bar, RS (1975). "Antibodies that impair insulin receptor binding in an unusual diabetic syndrome with severe insulin resistance". Science. 190 (4209): 63–5. doi:10.1126/science.170678. PMID   170678.
  8. ↑ Kahn, CR; Kasuga, M; King, GL; Grunfeld, C (1982). "Autoantibodies to insulin receptors in man: immunological determinants and mechanism of action". Ciba Foundation symposium (90): 91–113. PMID   6183063.
  9. ↑ Kahn, CR; Baird, KL; Jarrett, DB; Flier, JS (1978). "Direct demonstration that receptor crosslinking or aggregation is important in insulin action". Proceedings of the National Academy of Sciences of the United States of America. 75 (9): 4209–13. doi:10.1073/pnas.75.9.4209. PMC   336081  Lock-green.svg. PMID   279910.
  10. ↑ Moller, DE; Flier, JS (1988). "Detection of an alteration in the insulin-receptor gene in a patient with insulin resistance, acanthosis nigricans, and the polycystic ovary syndrome (type a insulin resistance)". The New England Journal of Medicine. 319 (23): 1526–9. doi:10.1056/NEJM198812083192306. PMID   2460770.
  11. ↑ Moller, DE; Yokota, A; White, MF; Pazianos, AG; Flier, JS (1990). "A naturally occurring mutation of insulin receptor alanine 1134 impairs tyrosine kinase function and is associated with dominantly inherited insulin resistance". The Journal of Biological Chemistry. 265 (25): 14979–85. PMID   2168397.
  12. 1 2 Flier JS, Maratos-Flier E (1990). "Biology of Obesity". Harrison's Principles of Internal Medicine.
  13. ↑ Flier, JS (2004). "Obesity wars: molecular progress confronts an expanding epidemic". Cell. 116 (2): 337–50. doi:10.1016/S0092-8674(03)01081-X. PMID   14744442.
  14. 1 2 Flier JS, Maratos-Flier E (September 2007). "What fuels fat". Scientific American.
  15. ↑ Flier, JS; Cook, KS; Usher, P; Spiegelman, BM (1987). "Severely impaired adipsin expression in genetic and acquired obesity". Science. 237 (4813): 405–8. doi:10.1126/science.3299706. PMID   3299706.
  16. ↑ Lowell, BB; S-Susulic, V; Hamann, A; Lawitts, JA; Himms-Hagen, J; Boyer, BB; Kozak, LP; Flier, JS (1993). "Development of obesity in transgenic mice after genetic ablation of brown adipose tissue". Nature. 366 (6457): 740–2. doi:10.1038/366740a0. PMID   8264795.
  17. 1 2 Shimada, M; Tritos, NA; Lowell, BB; Flier, JS; Maratos-Flier, E (1998). "Mice lacking melanin-concentrating hormone are hypophagic and lean". Nature. 396 (6712): 670–4. doi:10.1038/25341. PMID   9872314.
  18. ↑ Kokoeva, MV; Yin, H; Flier, JS (2005). "Neurogenesis in the hypothalamus of adult mice: potential role in energy balance". Science. 310 (5748): 679–83. doi:10.1126/science.1115360. PMID   16254185.
  19. ↑ Badman, MK; Pissios, P; Kennedy, AR; Koukos, G; Flier, JS; Maratos-Flier, E (2007). "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): 426–37. doi:10.1016/j.cmet.2007.05.002. PMID   17550778.
  20. ↑ Ahima, RS; Prabakaran, D; Mantzoros, C; Qu, D; Lowell, B; Maratos-Flier, E; Flier, JS (1996). "Role of leptin in the neuroendocrine response to fasting". Nature. 382 (6588): 250–2. doi:10.1038/382250a0. PMID   8717038.
  21. ↑ Howard, JK; Cave, BJ; Oksanen, LJ; Tzameli, I; Bjørbaek, C; Flier, JS (2004). "Enhanced leptin sensitivity and attenuation of diet-induced obesity in mice with haploinsufficiency of Socs3". Nature Medicine. 10 (7): 734–8. doi:10.1038/nm1072. PMID   15220914.
  22. ↑ "Flier and Maratos-Flier Research Lab at Beth Israel Deaconess Medical Center".
  23. ↑ "Sarah Flier, MD, Joins BIDMC". 1 September 2010. Retrieved 2010-09-29.
  24. ↑ "Brigham and Women's Alumni in Academia". 1 September 2010. Retrieved 2010-09-29.
  25. ↑ "Jeffrey S. Flier, MD, Receives American Diabetes Association's Distinguished Research Award" (PDF). 9 June 2008. Retrieved 2010-10-18.
  26. ↑ "Graduation Ceremony, McEwan Hall: Honorary Graduate: Jeffrey S. Flier". 2010. Retrieved 2010-10-18.
  27. ↑ "NIDDK Welcomes Five New Members to Advisory Council". 11 March 2005. Retrieved 2010-10-18.
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