Gregory Ku, MD, PhD

Professor
Diabetes Center

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: 

A Whole Genome RNA Interference Screen Reveals a Role for Spry2 in Insulin Transcription and the Unfolded Protein Response.

Diabetes

Pappalardo Z, Chopra DG, Hennings TG, Richards H, Choe J, Yang K, Baeyens L, Ang K, Chen S, Arkin M, German MS, McManus MT, Ku GM

Gai/o-coupled receptor signaling restricts pancreatic ß-cell expansion.

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

Berger M, Scheel DW, Macias H, Miyatsuka T, Kim H, Hoang P, Ku GM, Honig G, Liou A, Tang Y, Regard JB, Sharifnia P, Yu L, Wang J, Coughlin SR, Conklin BR, Deneris ES, Tecott LH, German MS

Menin determines K-RAS proliferative outputs in endocrine cells.

The Journal of clinical investigation

Chamberlain CE, Scheel DW, McGlynn K, Kim H, Miyatsuka T, Wang J, Nguyen V, Zhao S, Mavropoulos A, Abraham AG, O'Neill E, Ku GM, Cobb MH, Martin GR, German MS

Research resource: RNA-Seq reveals unique features of the pancreatic ß-cell transcriptome.

Molecular endocrinology (Baltimore, Md.)

Ku GM, Kim H, Vaughn IW, Hangauer MJ, Myung Oh C, German MS, McManus MT

An siRNA screen in pancreatic beta cells reveals a role for Gpr27 in insulin production.

PLoS genetics

Ku GM, Pappalardo Z, Luo CC, German MS, McManus MT