Suneil Koliwad, MD, PhD

Associate Professor
Diabetes Center
Research Overview: 

My laboratory investigates the role of chronic inflammation in the development of Type 2 Diabetes and how dietary lipids modulate the activation of innate immune cells that trigger and maintain inflammation in metabolic tissues.

Beyond comprising our bodily energy stores, dietary lipids are necessary for several critical processes, including the synthesis of cellular membranes, vitamins, skin lipids and waxes, blood clotting, gene expression, and cell signaling cascades. However, when chronically in excess, dietary fat intake is associated with several diseases, including diabetes, neurodegenerative diseases, certain cancers, and atherosclerosis, which together exact a huge toll on human health. Given the high prevalence of high-fat diets in our world, determining the links between dietary lipids and these diseases is of biomedical and socioeconomic importance. 

One emerging possibility involves chronic inflammation. Excess dietary fat intake often produces tissue inflammation that manifests prior to disease onset. For type 2 diabetes, this process is characterized by the inflammatory (M1) activation of innate immune cells, including macrophages and dendritic cells, in metabolic tissues such as white adipose, muscle, and liver. In exploring how dietary lipids may act as proximal triggers of macrophage activation, we showed that genetically-altered murine macrophages with an increased capacity to store dietary fats as intracellular triacylglycerol are less vulnerable to M1 inflammatory activation both in culture and in living mice. Remarkably, by transplanting these protective macrophages into mice protected them against developing diabetes driven by diet-induced obesity.

We are now deeply focused on probing the mechanisms by which intracellular fatty acids modulate inflammatory activation in macrophages, dendritic cells, and CNS microglia and determine how these impact type 2 diabetes, neurodegeneration, and other diseases in which chronic inflammation precedes overt disease.

Primary Thematic Area: 
Tissue / Organ Biology & Endocrinology
Secondary Thematic Area: 
Immunology
Research Summary: 
The Intersection between Dietary Lipids, Inflammation, and Metabolic Disease

Websites

Publications: 

Microglial Lipid Biology in the Hypothalamic Regulation of Metabolic Homeostasis.

Frontiers in endocrinology

Folick A, Koliwad SK, Valdearcos M

Autoregulation of insulin receptor signaling through MFGE8 and the αvβ5 integrin.

Proceedings of the National Academy of Sciences of the United States of America

Datta R, Lizama CO, Soltani AK, Mckleroy W, Podolsky MJ, Yang CD, Huynh TL, Cautivo KM, Wang B, Koliwad SK, Abumrad NA, Atabai K

Invariant natural killer T cells coordinate removal of senescent cells.

Med

Shivani Arora, Peter J. Thompson, Yao Wang, Aritra Bhattacharyya, Hara Apostolopoulou, Rachel Hatano, Ram P. Naikawadi, Ajit Shah, Paul J. Wolters, Suneil Koliwad, Mallar Bhattacharya, Anil Bhushan