Christine Kusminski, Ph.D. Associate Professor School Medical School Department Internal Medicine Biography Christine Kusminski, Ph.D., is an Associate Professor in the Department of Internal Medicine and the Touchstone Diabetes Center at UT Southwestern Medical Center. Originally from the United Kingdom, Dr. Kusminski holds a bachelor's degree in biochemistry from the University of Cardiff, where she graduated with honors. She completed her doctoral degree in biomedical sciences at the University of Warwick in England. Dr. Kusminski joined the UT Southwestern faculty in 2013, bringing along her expertise in adipose tissue function, mitochondrial bioenergetics and energy homeostasis. Dr. Kusminski's primary research interests are in the area of obesity and type 2 diabetes (T2D). Specifically, exploring the mechanisms by which white adipose tissue function impacts lipid metabolism and system-wide metabolic homeostasis. Her early research examined the mechanisms by which mitochondrial dysfunction impacts adipose tissue expansion during obesity. She developed a novel genetic tool that proved instrumental in altering mitochondrial activity in an inducible cell-type specific manner, such as the adipocyte, through modulation of mitochondrial proteins, such as mitoNEET and mitochondrial ferritin. Her mitoNEET research detailed the generation of the most obese, heaviest mus musculus reported to date, 130 g in body weight and the equivalent of a 600 lb human. mitoNEET was shown to drive metabolically healthy obesity, indicating that the alteration in mitochondrial bioenergetics in white adipose tissue is a powerful approach to study obesity. Recently, the primary focus of Dr Kusminski’s lab has centered around the mechanisms of the globally successful multi-receptor agonist drugs that target the incretin receptors, which elicit beneficial metabolic effects for the treatment of obesity and T2D. In particular, how the addition of GIP receptor (GIPR) agonism to GLP-1 receptor (GLP-1R) agonism provides an improved therapeutic profile. Her lab examines the in vivo peripheral mechanisms of GIPR action in white adipose tissue in a preclinical setting. Her recent research entailed the generation of a novel mouse model of adipose tissue-specific induction of the GIPR. Her lab demonstrated that GIPR activation in the fat cell protects mice from weight gain during diet-induced obesity, and triggers profound weight loss (~35%) under obese conditions. They further showed that activation of the GIPR in adipose tissue increases local lipid oxidation and thermogenesis, in addition to enhancing energy expenditure. Mechanistically, her lab reported that GIPR induction upregulates specific energy-wasting processes, by activating SERCA-mediated futile calcium cycling pathways in the white adipocyte. GIPR activation also triggered a unique metabolic memory effect that prevented weight regain, i.e., temporary induction of GIPR in the adipocyte lead to permanent changes in weight loss, highlighted an new aspect in adipocyte biology. Her research put forward a molecular mechanism for the peripheral action of GIPR in white adipose tissue, which triggers favorable metabolic effects on body weight and energy balance. Her studies should contribute to the understanding of how GLP-1R/GIPR co-agonists increase energy expenditure to promote weight loss in obesity. Her research further brings to light the GIPR in the adipocyte as a meaningful target for the development of future incretin-based therapeutic interventions for the treatment of obesity. Dr Kusminski’s research findings have resulted in numerous articles in peer-reviewed publications, reviews, book chapters and media. Education Undergraduate Cardiff University (2003), Biochemistry Graduate School Univ of Warwick (2007), Biomedical Sciences Research Interest The mechanisms of GIP receptor action in white adipose tissue in the context of obesity and type 2 diabetes The regulation of lipid metabolism in adipose tissue function and system-wide energy balance Publications Featured Publications The GIP receptor activates futile calcium cycling in white adipose tissue to increase energy expenditure and drive weight loss in mice. Yu X, Chen S, Funcke JB, Straub LG, Pirro V, Emont MP, Droz BA, Collins KA, Joung C, Pearson MJ, James CM, Babu GJ, Efthymiou V, Vernon A, Patti ME, An YA, Rosen ED, Coghlan MP, Samms RJ, Scherer PE, Kusminski CM, Cell Metab 2024 Dec A Mechanistic Rationale for Incretin-Based Therapeutics in the Management of Obesity. Samms RJ, Kusminski CM, Annu Rev Physiol 2024 Nov Transforming obesity: The advancement of multi-receptor drugs. Kusminski CM, Perez-Tilve D, Müller TD, DiMarchi RD, Tschöp MH, Scherer PE, Cell 2024 Jul 187 15 3829-3853 Targeting adipose tissue in the treatment of obesity-associated diabetes. Kusminski CM, Bickel PE, Scherer PE Nat Rev Drug Discov 2016 Jun MitoNEET-driven alterations in adipocyte mitochondrial activity reveal a crucial adaptive process that preserves insulin sensitivity in obesity. Kusminski CM, Holland WL, Sun K, Park J, Spurgin SB, Lin Y, Askew GR, Simcox JA, McClain DA, Li C, Scherer PE Nat. Med. 2012 Oct 18 10 1539-49 Mitochondrial dysfunction in white adipose tissue. Kusminski CM, Scherer PE Trends Endocrinol. Metab. 2012 Sep 23 9 435-43 MitoNEET-Parkin Effects in Pancreatic a- and ?-Cells, Cellular Survival and Intra-Insular Crosstalk. Kusminski CM, Chen S, Ye R, Sun K, Wang QA, Spurgin SB, Sanders PE, Brozinick JT, Li WH, Unger RH, Scherer PE Diabetes 2016 Feb MitoNEET-mediated effects on browning of white adipose tissue. Kusminski CM, Park J, Scherer PE Nat Commun 2014 5 3962 Diabetes and apoptosis: lipotoxicity. Kusminski CM, Shetty S, Orci L, Unger RH, Scherer PE Apoptosis 2009 Dec 14 12 1484-95 Results 1-9 of 9 1 Honors & Awards JDRF AwardPostdoctoral Research Fellowship Grant (2007) ASO AwardPh.D. Student Research of the Year Award, Association for the Study of Obesity, London, UK (2006) Albert Renold AwardFellowship Award from the European Foundation for the Study of Diabetes (EFSD), Dusseldorf, Germany (2005) Professional Associations/Affiliations American Diabetes Association (2014-2024) American Heart Association (2013)