Christine Kusminski, Ph.D.

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.