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Research Interest

My group is interested in inter-organ communication in various metabolic disease states, such as obesity, diabetes, and cancer. Lipids, both derived from food and released from organs such as adipose tissue, are important mediators of this tissue crosstalk. We have previously shown that the transcription factors TBL1 and TBLR1 are critical regulators of lipid metabolism in multiple organs such as liver and adipose tissue (Rohm et al. 2013, Kulozik et al. 2011). By regulating lipid storage and usage, TBL1 and TBLR1 are involved in the development of type 2 diabetes and associated diseases such as fatty liver disease and lipotoxicity. Pancreatic beta-cells are particularly prone to lipotoxicity, which is one of the factors involved in progressive beta-cell failure in diabetes, mediated by defective tissue crosstalk in the diseased state.

Project

Transcriptional control of pancreatic beta-cells by TBL1/TBLR1

While we do not yet know how TBL1/TBLR1 are involved in beta-cell function, preliminary data shows that TBL1 levels are dysregulated in islets of obese diabetic mice, indicating that these transcription factors are indeed important for beta-cell function in hyperglycemic/ dyslipidemic conditions. In the present project, using both in vitro cell culture models and beta-cell specific TBL1/TBLR1 knockout mice, we will investigate how these transcription factors regulate beta-cell function (and subsequent whole-body physiology) under various disease conditions, and how we can target them to fight diabetes. In our collaboration with the Alberta Diabetes Institute, the successful PhD candidate will further characterize the TBL1/TBLR1 deficient beta-cells using Calcium imaging and patch clamping, and expand findings to human pancreatic islets.

Publications

Rohm M, et al. (2013) Transcriptional cofactor TBLR1 controls lipid mobilization in white adipose tissue. Cell Metab. 2013 Apr 2;17(4):575-85.

Kulozik P, et al. (2011) Hepatic deficiency in transcriptional cofactor TBL1 promotes liver steatosis and hypertriglyceridemia. Cell Metab. 2011 Apr 6;13(4):389-400.