Wikipedia

Gökhan S. Hotamisligil

Gökhan S. Hotamisligil (Turkish: Gökhan Sıddık Hotamışlıgil;[1] born June 24, 1962) is a Turkish-American physician scientist; James Stevens Simmons Chair of Genetics and Metabolism at Harvard T.H. Chan School of Public Health (HSPH); Director of the Harvard Chan Center on Causes and Prevention of Cardiovascular Disease (CAP-CVD)[2] and associate member of Harvard-MIT Broad Institute, Harvard Stem Cell Institute and the Joslin Diabetes Center.[3]

Gökhan S. Hotamisligil
Born (1962-06-24) June 24, 1962 (age 62)
Rize, Turkey
CitizenshipTurkey and US
Alma materAnkara University (MD, 1986)
Harvard University (PhD, 1994)
SpouseSelen Ciliv Hotamisligil
Children2
Scientific career
FieldsMetabolism, obesity, diabetes, atherosclerosis
InstitutionsHarvard T.H. Chan School of Public Health

Hotamisligil has been a pioneer in research efforts to explain the mechanistic basis of common chronic metabolic diseases; particularly obesity, diabetes, fatty liver disease, and atherosclerosis. His work has led to the emergence of novel concepts that have altered the understanding of metabolic disease pathogenesis.[4]

Biography

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Gökhan Hotamisligil was born in Rize, Turkey and after attending elementary schools in Vakfikebir, Turgutlu, and Gediz; he graduated from the public Ankara Atatürk Anadolu High School in 1980. He then received his degree in medicine from Ankara University Medical School in 1986 and his PhD from Harvard Medical School (HMS) in 1994. Hotamisligil joined the Harvard T.H. Chan School of Public Health (HSPH) as an assistant professor in the Department of Nutrition & Division of Biological Sciences. He was promoted to tenured professor in 2003. He founded the Department of Genetics & Complex Diseases in the same year and served as the chair of the department for 16 years.[5]

From 2014 to 2024, the Sabri Ülker Center for Nutrient, Genetic, and Metabolic Research at HSPH was established by the Ülker family to honor their late father Sabri Ülker and to support the research in the laboratory of Hotamisligil.[6]

Hotamisligil has been recognized with many fellowships and awards over the course of his career. These include election as a fellow of the American Association for the Advancement of Science,[7] the Naomi Berrie Award for Outstanding Achievement in Diabetes Research,[8] the Outstanding Scientific Accomplishment Award from the American Diabetes Association,[9] the Wertheimer Award for Outstanding Basic Research Contributions in the field of obesity from IASO,[10] the Danone International Prize for Nutrition,[11] the Roy Greep Award for Outstanding Research from the Endocrine Society,[12] EASD–Novo Nordisk Foundation Diabetes Prize for Excellence,[13] , The John K. and Mary E. Davidson Lectureship Award[14], among others.

He was featured as an exhibitor for his project "Molecular Architecture" in a join exhibit with Refik Anadol Studios at Venice Biennale in 2024. He has also been the recipient of 2004 TUBITAK Science Award,[15] Koç Science Award[16][17] and elected member of the Turkish Academy of Sciences. He also serves as a member of the board of trustees of Kadir Has University. Hotamisligil serves in many editorial boards including Science Translational Medicine, Cell Metabolism, EMBO molecular Medicine, Journal of Clinical Investigation, PlosBiology, and others.

Research

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Hotamisligil’s research efforts focus on the molecular and genetic basis of common and complex diseases, particularly those associated with obesity and aging including diabetes, carvdiovascular disease, fatty liver disease, and asthma. His research examines the mechanisms of nutrient sensing and response pathways as they relate to immune and metabolic homeostasis. Hotamisligil’s work has been instrumental in the emergence of the immunological basis of obesity and diabetes and the field of immunometabolism[18],[19],.[4] Today obesity and diabetes are understood as states of chronic, low-grade, sustained, systemic and metabolically orchestrated inflammation; also known as “metaflammation,” a concept introduced by Hotamisligil; which underlies the pathogenesis of metabolic diseases.

In a 1997 paper, Hotamışlıgil lab published a study showing that genetic ablation of an inflammatory mediator or its receptor in  obese mice resulted in the improvement of insulin sensitivity and glucose metabolism.  This study provided definitive proof that metaflammation was a critical component of chronic metabolic diseases.

In a 2002 paper, the Hotamisligil lab established a link between activation of the inflammatory and stress kinase JNK and consequent inhibition of insulin receptor signaling via phosphorylation of the insulin receptor substrate (IRS-1).[20] Since then, his lab has identified multiple other significant molecules and pathways as key modulators of chronic metabolic inflammation, insulin sensitivity and glucose metabolism in obesity, including the double stranded RNA dependent protein kinase PKR[21] and the transmembrane protein STAMP2.[22][23]

The Hotamisligil lab also established the importance of organelle homeostasis in metabolic tissues and the role of organelle dysfunction in metabolic disease. In particular, they established that chronic endoplasmic reticulum (ER) dysfunction is a feature of metabolic tissues in obesity,[24] linked to regulation of insulin action and glucose and lipid metabolism. In subsequent studies they showed that the increase in ER stress in the obese condition is in part related to defects in autophagy, the cellular recycling system,[25] as well as changes in lipid metabolism and ER membrane composition and result in alterations ER calcium homeostasis.[26] Recently, the Hotamisligil lab also delineated abnormal interactions between ER and mitochondria in the context of metabolic disease that result in aberrant calcium metabolism and mitochondrial dysfunction.[27] More recently, Hotamisligil lab performed the most detailed molecular architectural analysis of subcellular structures in hepatocytes, in their native liver tissue environment in leand obese liver and during feeding and fasting cycles.  These pioneering studies demonstrated the structural changes that are caused by obesity and nutritional status and defined a novel mechanism of metabolic homeostasis through molecular architectural regulation[28]

Hotamisligil lab integrates these cellular and molecular stress pathways to nutrients through their work in an integrated field on lipid trafficking and signaling with a focus on fatty acid binding proteins,[29] de novo lipogenesis products, and new hormones.[30] In a 2008 paper, Hotamisligil lab described a lipid natured hormone, which they named as a “lipokine” and showed its beneficial actions on lipid and glucose metabolism.[31] In 2015, Hotamisligil lab described a novel hormone that is produced by the adipose tissue during fasting to regulate hepatic glucose production and pancreatic activity.[32] Therapeutic targeting of both of these molecules is pursued for the treatment of metabolic diseases.[33] In a 2017 paper, Hotamisligil lab has identified a transcription factor, NRF1, that both senses and responds to excess cholesterol in the ER[34] and acts together with SREBP2 as yin-yang to keep ER cholesterol levels within a safe, narrow range.[35] The lab also defined the mechanism of interactions between these two critical pathways controlling cholesterol balance.  Additional studies demonstrated that NRF1 is a critical defender of metabolic homeostasis under the most challenging of conditions, such as brown adipose tissue challenged by cold, or the integrity of the cells with the highest secretory demands[36].

In 2022, Hotamisligil lab described the discovery of a new hormone complex called Fabkin, formed by FABP4-ADK-NDPK proteins and defined its molecular mechanism of action[37].  These studies also demonstrated a remarkable therapeutic activity of targeting this complex in both type 1 and type 2 diabetes.  The lab now pursues innovative collaborative models to realize the translational potential of this target and pursuing paths towards clinical applications

As of 2025, Hotamisligil has authored over 200 publications, which have received in excess of 85,000 citations and was named as an inventor on multiple patents.[5][38] He has an h-index of 115.[5] Hotamisligil has also been a mentor to many students and fellows who are now pursuing their independent scientific careers in many capacities around the world.[39] He has been an advocate of science as a vehicle of diplomacy between cultures and delivered more than 500 lectures around the world.[5]

Personal life

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Hotamisligil is married to Selen Ciliv, a physician scientist specialized in assisted infertility treatment technologies and clinical applications and a consultant to World Health Organization.[40] Their two children Leyla and Derin live in the United States and Canada.[41] His late father Hulki Hotamisligil was a physician and mother Güner Hotamisligil was a teacher who served in remote regions of Turkey to support public health and education.[42][43]

Selected awards

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1991 Lucille P. Markey Predoctoral Fellowship in Developmental Biology[5]

1997 Pew Scholar in Biomedical Sciences, Pew Charitable Trusts[5]

2004 Recipient of the Turkish Scientific and Research Council, TUBITAK Award[15]

2007 Outstanding Scientific Accomplishment Award, American Diabetes Association[9]

2009 Elected Fellow of American Association for Advancement of Science[7]

2010 Wertheimer Award, International Association for the Study of Obesity[10]

2010 Naomi Berrie Award for Outstanding Achievement in Diabetes Research[8]

2012 Richard J. Havel Lecture[5]

2013 Koç Foundation Science Award[16][17]

2014 Danone International Prize for Nutrition[11]

2015 Roy O. Greep Award for Outstanding Research, Endocrine Society[12]

2017 Hans L. Falk Memorial Lecture[44]

2018 EASD–Novo Nordisk Foundation Diabetes Prize for Excellence[13]

2019 Keystone Symposia-- Immunometabolism, Metaflammation and Metabolic Disorders[45]

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References

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  1. ^ Yılmaz, Sedat (8 October 2014). "Parayı Harvard'a değil Türkiye'ye bağışladı" (in Turkish). Yeni Akit. Archived from the original on 26 December 2020. Retrieved 27 December 2020. Gökhan Sıddık Hotamışlıgil oldukça uzun bir isim ve söylenmesi zor. Bana bazen 'Hotalar' diyorlar. Ancak daha çok Gökhan'ı kısaltarak Amerikalılar Doktor G (Ci) deyip kolayı seçiyorlar. Hakikaten yurt dışında söylenişi zor isim sıkıntılı" diye konuştu.
  2. ^ "Center on Causes and Prevention of Cardiovascular Disease". Center on Causes and Prevention of Cardiovascular Disease. 2025-04-01. Retrieved 2025-04-01.
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  4. ^ a b Hotamisligil, Gökhan S. (February 8, 2017). "Inflammation, metaflammation and immunometabolic disorders". Nature. 542 (7640): 177–185. Bibcode:2017Natur.542..177H. doi:10.1038/nature21363. ISSN 1476-4687. PMID 28179656. S2CID 205253771.
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  18. ^ Hotamisligil, G. S.; Shargill, N. S.; Spiegelman, B. M. (1993-01-01). "Adipose expression of tumor necrosis factor-alpha: direct role in obesity-linked insulin resistance". Science. 259 (5091): 87–91. Bibcode:1993Sci...259...87H. doi:10.1126/science.7678183. ISSN 0036-8075. PMID 7678183.
  19. ^ Hotamisligil, Gökhan S. (2006-12-14). "Inflammation and metabolic disorders". Nature. 444 (7121): 860–867. Bibcode:2006Natur.444..860H. doi:10.1038/nature05485. ISSN 1476-4687. PMID 17167474. S2CID 4424156.
  20. ^ Hirosumi, Jiro; Tuncman, Gürol; Chang, Lufen; Görgün, Cem Z.; Uysal, K. Teoman; Maeda, Kazuhisa; Karin, Michael; Hotamisligil, Gökhan S. (2002-11-21). "A central role for JNK in obesity and insulin resistance". Nature. 420 (6913): 333–336. Bibcode:2002Natur.420..333H. doi:10.1038/nature01137. ISSN 0028-0836. PMID 12447443. S2CID 1659156.
  21. ^ Nakamura, Takahisa; Furuhashi, Masato; Li, Ping; Cao, Haiming; Tuncman, Gurol; Sonenberg, Nahum; Gorgun, Cem Z.; Hotamisligil, Gökhan S. (2010-02-05). "Double-stranded RNA-dependent protein kinase links pathogen sensing with stress and metabolic homeostasis". Cell. 140 (3): 338–348. doi:10.1016/j.cell.2010.01.001. ISSN 1097-4172. PMC 2820414. PMID 20144759.
  22. ^ Wellen, Kathryn E.; Fucho, Raquel; Gregor, Margaret F.; Furuhashi, Masato; Morgan, Carlos; Lindstad, Torstein; Vaillancourt, Eric; Gorgun, Cem Z.; Saatcioglu, Fahri (2007-05-04). "Coordinated regulation of nutrient and inflammatory responses by STAMP2 is essential for metabolic homeostasis". Cell. 129 (3): 537–548. doi:10.1016/j.cell.2007.02.049. ISSN 0092-8674. PMC 2408881. PMID 17482547.
  23. ^ ten Freyhaus, Henrik; Calay, Ediz S.; Yalcin, Abdullah; Vallerie, Sara N.; Yang, Ling; Calay, Zerrin Z.; Saatcioglu, Fahri; Hotamisligil, Gökhan S. (2012-07-03). "Stamp2 controls macrophage inflammation through nicotinamide adenine dinucleotide phosphate homeostasis and protects against atherosclerosis". Cell Metabolism. 16 (1): 81–89. doi:10.1016/j.cmet.2012.05.009. ISSN 1932-7420. PMC 4163924. PMID 22704678.
  24. ^ Ozcan, Umut; Cao, Qiong; Yilmaz, Erkan; Lee, Ann-Hwee; Iwakoshi, Neal N.; Ozdelen, Esra; Tuncman, Gürol; Görgün, Cem; Glimcher, Laurie H. (2004-10-15). "Endoplasmic reticulum stress links obesity, insulin action, and type 2 diabetes". Science. 306 (5695): 457–461. Bibcode:2004Sci...306..457O. doi:10.1126/science.1103160. ISSN 1095-9203. PMID 15486293. S2CID 22517395.
  25. ^ Yang, Ling; Li, Ping; Fu, Suneng; Calay, Ediz S.; Hotamisligil, Gökhan S. (2010-06-09). "Defective hepatic autophagy in obesity promotes ER stress and causes insulin resistance". Cell Metabolism. 11 (6): 467–478. doi:10.1016/j.cmet.2010.04.005. ISSN 1932-7420. PMC 2881480. PMID 20519119.
  26. ^ Fu, Suneng; Yang, Ling; Li, Ping; Hofmann, Oliver; Dicker, Lee; Hide, Winston; Lin, Xihong; Watkins, Steven M.; Ivanov, Alexander R. (2011-05-26). "Aberrant lipid metabolism disrupts calcium homeostasis causing liver endoplasmic reticulum stress in obesity". Nature. 473 (7348): 528–531. Bibcode:2011Natur.473..528F. doi:10.1038/nature09968. ISSN 1476-4687. PMC 3102791. PMID 21532591.
  27. ^ Arruda, Ana Paula; Pers, Benedicte M.; Parlakgül, Güneş; Güney, Ekin; Inouye, Karen; Hotamisligil, Gökhan S. (December 2014). "Chronic enrichment of hepatic endoplasmic reticulum-mitochondria contact leads to mitochondrial dysfunction in obesity". Nature Medicine. 20 (12): 1427–1435. doi:10.1038/nm.3735. ISSN 1546-170X. PMC 4412031. PMID 25419710.
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  29. ^ Hotamisligil, Gökhan S.; Bernlohr, David A. (October 2015). "Metabolic functions of FABPs--mechanisms and therapeutic implications". Nature Reviews. Endocrinology. 11 (10): 592–605. doi:10.1038/nrendo.2015.122. ISSN 1759-5037. PMC 4578711. PMID 26260145.
  30. ^ Yilmaz, Mustafa; Claiborn, Kathryn C.; Hotamisligil, Gökhan S. (July 2016). "De Novo Lipogenesis Products and Endogenous Lipokines". Diabetes. 65 (7): 1800–1807. doi:10.2337/db16-0251. ISSN 1939-327X. PMC 4915584. PMID 27288005.
  31. ^ Cao, Haiming; Gerhold, Kristin; Mayers, Jared R.; Wiest, Michelle M.; Watkins, Steven M.; Hotamisligil, Gökhan S. (2008-09-19). "Identification of a lipokine, a lipid hormone linking adipose tissue to systemic metabolism". Cell. 134 (6): 933–944. doi:10.1016/j.cell.2008.07.048. ISSN 1097-4172. PMC 2728618. PMID 18805087.
  32. ^ Ertunc, Meric Erikci; Sikkeland, Jørgen; Fenaroli, Federico; Griffiths, Gareth; Daniels, Mathew P.; Cao, Haiming; Saatcioglu, Fahri; Hotamisligil, Gökhan S. (February 2015). "Secretion of fatty acid binding protein aP2 from adipocytes through a nonclassical pathway in response to adipocyte lipase activity". Journal of Lipid Research. 56 (2): 423–434. doi:10.1194/jlr.M055798. ISSN 1539-7262. PMC 4306695. PMID 25535287.
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  36. ^ Widenmaier, Scott B.; Snyder, Nicole A.; Nguyen, Truc B.; Arduini, Alessandro; Lee, Grace Y.; Arruda, Ana Paula; Saksi, Jani; Bartelt, Alexander; Hotamisligil, Gökhan S. (2017-11-16). "NRF1 Is an ER Membrane Sensor that Is Central to Cholesterol Homeostasis". Cell. 171 (5): 1094–1109.e15. doi:10.1016/j.cell.2017.10.003. ISSN 1097-4172. PMID 29149604.
  37. ^ Prentice, Kacey J.; Saksi, Jani; Robertson, Lauren T.; Lee, Grace Y.; Inouye, Karen E.; Eguchi, Kosei; Lee, Alexandra; Cakici, Ozgur; Otterbeck, Emily; Cedillo, Paulina; Achenbach, Peter; Ziegler, Anette-Gabriele; Calay, Ediz S.; Engin, Feyza; Hotamisligil, Gökhan S. (December 2021). "A hormone complex of FABP4 and nucleoside kinases regulates islet function". Nature. 600 (7890): 720–726. doi:10.1038/s41586-021-04137-3. ISSN 1476-4687.
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  40. ^ "Steps through the Revision Process of Reproductive Health Sections of ICD-11". karger.com. Retrieved 2017-06-05.
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