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: 

The Impact of Insulin Resistance on Loss of Lung Function and Response to Treatment in Asthma.

American journal of respiratory and critical care medicine

Peters MC, Schiebler M, Cardet JC, Johansson MW, Sorkness R, DeBoer MD, Bleecker ER, Meyers DA, Castro M, Sumino K, Erzurum SC, Tattersall MC, Zein JG, Hastie AT, Moore W, Levy BD, Israel E, Duvall M, Phillips BR, Mauger DT, Wenzel SE, Fajt ML, Koliwad SK, Denlinger LC, Woodruff PG, Jarjour NN, Fahy JV, National Heart Lung and Blood Institute Severe Asthma Research Program-3

Excess natural-cause deaths in California by cause and setting: March 2020 through February 2021.

PNAS nexus

Chen YH, Stokes AC, Aschmann HE, Chen R, DeVost S, Kiang MV, Koliwad S, Riley AR, Glymour MM, Bibbins-Domingo K

ASB4 modulates central melanocortinergic neurons and calcitonin signaling to control satiety and glucose homeostasis.

Science signaling

Vagena E, Crneta J, Engström P, He L, Yulyaningsih E, Korpel NL, Cheang RT, Bachor TP, Huang A, Michel G, Attal K, Berrios DI, Valdearcos M, Koliwad SK, Olson DP, Yi CX, Xu AW

Metabolic factors in the regulation of hypothalamic innate immune responses in obesity.

Experimental & molecular medicine

Folick A, Cheang RT, Valdearcos M, Koliwad SK

A Glycemia Risk Index (GRI) of Hypoglycemia and Hyperglycemia for Continuous Glucose Monitoring Validated by Clinician Ratings.

Journal of diabetes science and technology

Klonoff DC, Wang J, Rodbard D, Kohn MA, Li C, Liepmann D, Kerr D, Ahn D, Peters AL, Umpierrez GE, Seley JJ, Xu NY, Nguyen KT, Simonson G, Agus MSD, Al-Sofiani ME, Armaiz-Pena G, Bailey TS, Basu A, Battelino T, Bekele SY, Benhamou PY, Bequette BW, Blevins T, Breton MD, Castle JR, Chase JG, Chen KY, Choudhary P, Clements MA, Close KL, Cook CB, Danne T, Doyle FJ, Drincic A, Dungan KM, Edelman SV, Ejskjaer N, Espinoza JC, Fleming GA, Forlenza GP, Freckmann G, Galindo RJ, Gomez AM, Gutow HA, Heinemann L, Hirsch IB, Hoang TD, Hovorka R, Jendle JH, Ji L, Joshi SR, Joubert M, Koliwad SK, Lal RA, Lansang MC, Lee WA, Leelarathna L, Leiter LA, Lind M, Litchman ML, Mader JK, Mahoney KM, Mankovsky B, Masharani U, Mathioudakis NN, Mayorov A, Messler J, Miller JD, Mohan V, Nichols JH, Nørgaard K, O'Neal DN, Pasquel FJ, Philis-Tsimikas A, Pieber T, Phillip M, Polonsky WH, Pop-Busui R, Rayman G, Rhee EJ, Russell SJ, Shah VN, Sherr JL, Sode K, Spanakis EK, Wake DJ, Waki K, Wallia A, Weinberg ME, Wolpert H, Wright EE, Zilbermint M, Kovatchev B