Gregory Ku, MD, PhD

Assistant Professor
Diabetes Center
Research Overview: 

Our lab studies the pancreatic beta cell, the body’s primary source of insulin. Diabetes mellitus can only occur when the beta cell is either destroyed by autoimmunity (type 1) or can’t make enough insulin to meet the demands of increased insulin resistance (type 2). Therefore, we believe that the next generation of diabetes therapeutics will come from a better understanding of beta cell biology.

Using a whole genome RNA interference screen, we have identified ~20 novel regulators of insulin production in the beta cell. We have used genetic interaction maps to understand how these hits regulate insulin production. One of these hits is a new player in the unfolded protein response and another hit is a novel regulator of mitochondrial dynamics. We are also now studying the role of these and other hits in mice and tissue culture cells. We are also developing novel assays to allow high throughput RNAi and CRISPR screens for regulators of human pancreatic beta cell survival/proliferation and insulin secretion both in vivo and in vitro.

Primary Thematic Area: 
Tissue / Organ Biology & Endocrinology
Secondary Thematic Area: 
Human Genetics
Research Summary: 
Whole genome approaches to identify novel regulators of pancreatic beta cell function

Websites

Publications: 

Adhesion-mediated mechanosignaling forces mitohormesis.

Cell metabolism

Tharp KM, Higuchi-Sanabria R, Timblin GA, Ford B, Garzon-Coral C, Schneider C, Muncie JM, Stashko C, Daniele JR, Moore AS, Frankino PA, Homentcovschi S, Manoli SS, Shao H, Richards AL, Chen KH, Hoeve JT, Ku GM, Hellerstein M, Nomura DK, Saijo K, Gestwicki J, Dunn AR, Krogan NJ, Swaney DL, Dillin A, Weaver VM

Deletion of Gpr27 in vivo reduces insulin mRNA but does not result in diabetes.

Scientific reports

Chopra DG, Yiv N, Hennings TG, Zhang Y, Ku GM

A genetic interaction map of insulin production identifies Mfi as an inhibitor of mitochondrial fission.

Endocrinology

Lee J, Pappalardo Z, Chopra DG, Hennings TG, Vaughn I, Lan C, Choe JJ, Ang K, Chen S, Arkin M, McManus MT, German MS, Ku GM

In vivo Deletion of Beta Cell Drp1 Impairs Insulin Secretion without Affecting Islet Oxygen Consumption.

Endocrinology

Hennings TG, Chopra DG, DeLeon ER, VanDeusen HR, Sesaki H, Merrins MJ, Ku GM