Jeffrey Flier

Last updated
Jeffrey Flier
Jeffrey S. Flier.jpg
21st Dean of the Harvard Medical School
In office
September 1, 2007 July 31, 2016
Personal details
Born
Jeffrey Scott Flier

(1948-02-27) February 27, 1948 (age 76)
New York, New York
Spouse Eleftheria Maratos-Flier
Children2
Website Dean of the Faculty of Medicine

JeffreyFlier is an American physician, endocrinologist; widely cited scientist; the Higginson Professor of Medicine and Physiology at Harvard Medical School; and a Distinguished Service Professor at the same institution. He was the 21st Dean of the Faculty of Medicine at Harvard University from 2007 to 2016. [1] [2] [3]

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 (Kroll) Flier, who taught junior high school mathematics. [4] 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. [5] 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. [3] At BIDMC he served as a Chief Academic Officer from 2002 to 2007. [6]

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. [3] During his first year as dean, he led an extensive strategic planning process, releasing a report in October 2008. [7] 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. [8] His term as dean of Harvard Medical School ended in 2016 after nine years. [9]

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; [10] 2. successful launch and oversight of the $750 million “The World is Waiting” capital campaign; [11] 3. implementation of a major redesign of the preclinical medical curriculum; [12] 4. design and implementation of a new system for financial contributions to HMS from its affiliated institutions; [11] 5. establishment of a new department of biomedical informatics; [13] 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. [14] Flier's 2016 final class commencement speech at Harvard Medical School is available online. [15]

Research contributions

While at the Diabetes Branch of NIH, under the mentorship of Jesse Roth, Philip Gorden, and C. Ronald Kahn, Flier discovered the existence of autoantibodies to the insulin receptor as a cause of severe insulin resistance. [16] This discovery elucidated a rare cause of diabetes, [17] advanced the field of membrane receptor biology and provided an important tool for research on insulin action. [18] 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. [19] [20] Much of his research has addressed the pathophysiology of obesity; [21] [22] [23] In 1993, he described the dynamics of obesity in a brown-fat deficient, transgenic mouse model; [24] His most extensive work has related to the biology and pathophysiology of leptin, its physiological role in starvation, [25] and the molecular mechanisms of leptin resistance in obesity. [26] With Maratos-Flier, he studied the participation of neuropeptide MCH in feeding behavior and energy balance; [27] and the role of FGF21 in metabolic regulation. [28] With Bruce Spiegelman he discovered an altered production of adipsin in obesity in genetically obese mice. [29] In 2005, he reported the possible role of adult hypothalamic neurogenesis in the control of energy balance; [30] 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. [31] In 1980 he described a rare case of familial acanthosis nigricans-muscle cramps-acral enlargement syndrome. [32]

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 [33] and its sustainability, [34] enhancing US health provider workforce, [35] the pros and cons of prevailing credit attribution practices in academia and industry, [36] the realities and options linked to the irreproducibility of research results, [37] improving the institutional handling of scientific misconduct, [38] the obsolescence of distinctions between basic and translational biomedical research, [39] and the complexities behind conflict of interest (COI) disclosure. [40]

Flier has questioned the blanket and often ineffective approach toward DEI (diversity, equity, inclusion) initiatives. He does not support mandatory diversity statements in faculty applications. [41] He does not support the removal of historic portraits in universities (which are predominantly of white men) in order to provide more inclusive environments for historically underrepresented populations, like women and minorities. [42] Flier wants fairness for all, and he has critiqued the harmful “cancel culture”[ editorializing ]. He and other leaders have asked for an objective and fair-minded adjudication for Dr. David M. Sabatini, a biologist who was fired by the Howard Hughes Medical Institute and resigned from the Whitehead Institute and MIT following an allegation of sexual misconduct. [43]

Personal life

Flier is married to Eleftheria Maratos-Flier. She is an endocrinologist and Professor of Medicine at Harvard Medical School, [44] and currently a director of clinical research at Alynylam Pharmaceuticals. The two have collaborated in several areas of research. [27] [21] [23] They have two daughters. Sarah and Lydia, both of whom are physicians. [45]

Honors/affiliations/awards

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. [49]

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

Notes

Related Research Articles

Insulin resistance (IR) is a pathological condition in which cells either fail to respond normally to the hormone insulin or downregulate insulin receptors in response to hyperinsulinemia.

<span class="mw-page-title-main">Type 2 diabetes</span> Form of diabetes mellitus

Type 2 diabetes (T2D), formerly known as adult-onset diabetes, is a form of diabetes mellitus that is characterized by high blood sugar, insulin resistance, and relative lack of insulin. Common symptoms include increased thirst, frequent urination, fatigue and unexplained weight loss. Symptoms may also include increased hunger, having a sensation of pins and needles, and sores (wounds) that do not heal. Often symptoms come on slowly. Long-term complications from high blood sugar include heart disease, stroke, diabetic retinopathy which can result in blindness, kidney failure, and poor blood flow in the limbs which may lead to amputations. The sudden onset of hyperosmolar hyperglycemic state may occur; however, ketoacidosis is uncommon.

<span class="mw-page-title-main">Leptin</span> Hormone that inhibits hunger

Leptin also obese protein is a protein hormone predominantly made by adipocytes. Its primary role is likely to regulate long-term energy balance.

<span class="mw-page-title-main">Adipose tissue</span> Loose connective tissue composed mostly by adipocytes

Adipose tissue is a loose connective tissue composed mostly of adipocytes. It also 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. Its main role is to store energy in the form of lipids, although it also cushions and insulates the body.

<span class="mw-page-title-main">Adipocyte</span> 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 through adipogenesis. In cell culture, adipocyte progenitors can also form osteoblasts, myocytes and other cell types.

<span class="mw-page-title-main">Insulin-like growth factor 1</span> Protein found in humans

Insulin-like growth factor 1 (IGF-1), also called somatomedin C, is a hormone similar in molecular structure to insulin which plays an important role in childhood growth, and has anabolic effects in adults. In the 1950s IGF-1 was called "sulfation factor" because it stimulated sulfation of cartilage in vitro, and in the 1970s due to its effects it was termed "nonsuppressible insulin-like activity" (NSILA).

<span class="mw-page-title-main">Adiponectin</span> Mammalian protein found in Homo sapiens

Adiponectin is a protein hormone and adipokine, which is involved in regulating glucose levels and fatty acid breakdown. In humans, it is encoded by the ADIPOQ gene and is produced primarily in adipose tissue, but also in muscle and even in the brain.

<span class="mw-page-title-main">Resistin</span> Mammalian protein found in 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 peptide hormone derived from adipose tissue that in humans is encoded by the RETN gene.

<span class="mw-page-title-main">Fibroblast growth factor 21</span> Protein-coding gene in mammals

Fibroblast growth factor 21 is a protein that in mammals is encoded by the FGF21 gene. The protein encoded by this gene is a member of the fibroblast growth factor (FGF) family and specifically a member of the endocrine subfamily which includes FGF23 and FGF15/19. FGF21 is the primary endogenous agonist of the FGF21 receptor, which is composed of the co-receptors FGF receptor 1 and β-Klotho.

Glucagon-like peptide-1 (GLP-1) receptor agonists, also known as GLP-1 analogs, GLP-1DAs or incretin mimetics, are a class of drugs that reduce blood sugar and energy intake by activating the GLP-1 receptor. They mimic the actions of the endogenous incretin hormone GLP-1 that is released by the gut after eating.

Douglas L. Coleman was a scientist and professor emeritus at the Jackson Laboratory, in Bar Harbor, Maine. His work predicted that there exists a hormone that can cause mice to feel full, and that a mutation in the gene encoding this hormone can lead to obesity. The gene and corresponding hormone were discovered about 20 years later by Jeffrey M. Friedman, Rudolph Leibel, and their research teams at Rockefeller University, which Friedman named leptin.

<span class="mw-page-title-main">Rudolph Leibel</span>

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.

<span class="mw-page-title-main">Leonid Poretsky</span> American endocrinologist

Leonid Poretsky is a Russian-born American endocrinologist. His research interests include mechanisms of insulin action in the ovary, endocrinological aspects of AIDS, and clinical outcomes in diabetes. He has authored over 150 publications and has served on the National Institutes of Health's review committees and on the editorial boards of the Journal of Clinical Endocrinology and Metabolism and other endocrine journals.

<span class="mw-page-title-main">Jose F. Caro</span> American physician

José F. Caro 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 an artist and a signature member of the Pastel Society of America.

<span class="mw-page-title-main">Christos Socrates Mantzoros</span> Greek American physician and scientist

Christos Socrates Mantzoros is a Greek American physician-scientist, practicing internist-endocrinologist, teacher and researcher. He is a professor of medicine at Harvard Medical School and an adjunct professor at Boston University School of Medicine. He currently serves as the chief of endocrinology, diabetes and metabolism at the VA Boston Healthcare System, where he created de novo a leading academic division true to its tripartite mission and as the founding director of human nutrition at Beth Israel Deaconess Medical Center (BIDMC), Harvard Medical School. Finally, he holds the editor-in-chief position of the journal Metabolism: Clinical and Experimental.

<span class="mw-page-title-main">Sadaf Farooqi</span> British consultant physician

Ismaa Sadaf Farooqi 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.

<span class="mw-page-title-main">Pathophysiology of obesity</span> Physiological processes in obese people

Pathophysiology of obesity is the study of disordered physiological processes that cause, result from, or are otherwise associated with obesity. A number of possible pathophysiological mechanisms have been identified which may contribute in the development and maintenance of obesity.

Rexford Sefah Ahima is a professor of medicine, Public Health and Nursing; Bloomberg Distinguished Professor of Diabetes at the Johns Hopkins Medical School; and the Director of the Division of Endocrinology, Diabetes and Metabolism, Johns Hopkins University School of Medicine. Ahima's research focuses on central and peripheral actions of adipocyte hormones in energy homeostasis, and glucose and lipid metabolism.

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 on the neuroendocrine control of feeding behaviour. She is a contributing author to known textbooks and reviews in internal medicine, endocrinology, and physiology. Her marriage with professor Jeffrey Flier, was noted by Forbes as a lasting and productive bond between eminent medical scholars. They have two adult daughters who are also physicians. She is also known as Terry Maratos-Flier.

<span class="mw-page-title-main">Alexei Kharitonenkov</span> Russian biochemist

Alexei Kharitonenkov is a Russian-American researcher best known for his discoveries of endocrine functions of Fibroblast Growth Factor 21 (FGF21) and its prospects in developing novel therapies for metabolic diseases. He is also known for his landmark identification of the signal-regulatory family of proteins (SIRPs), and their corresponding protein-tyrosine phosphatases, which helped unveil the molecular machinery of immune self-recognition and their potential for the development of drugs to fight cancer.

References

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  20. 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. doi: 10.1016/S0021-9258(18)77212-8 . PMID   2168397.
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  23. 1 2 Flier JS, Maratos-Flier E (September 2007). "What fuels fat". Scientific American. 297 (3): 72–81. Bibcode:2007SciAm.297c..72F. doi:10.1038/scientificamerican0907-72. PMID   17784627.
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  26. 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. S2CID   8086930.
  27. 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. Bibcode:1998Natur.396..670S. doi:10.1038/25341. PMID   9872314. S2CID   4370377.
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  31. Shi, Hang; Kokoeva, Maia V.; Inouye, Karen; Tzameli, Iphigenia; Yin, Huali; Flier, Jeffrey S. (2006). "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.
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  45. "Sarah Flier, MD, Joins BIDMC". 1 September 2010. Retrieved 2010-09-29.
  46. "Jeffrey S. Flier, MD, Receives American Diabetes Association's Distinguished Research Award" (PDF). 9 June 2008. Archived from the original (PDF) on 9 March 2012. Retrieved 2010-10-18.
  47. "Graduation Ceremony, McEwan Hall: Honorary Graduate: Jeffrey S. Flier". 2010. Archived from the original on 2020-01-10. Retrieved 2010-10-18.
  48. "NIDDK Welcomes Five New Members to Advisory Council". 11 March 2005. Archived from the original on 20 December 2010. Retrieved 2010-10-18.
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