Research Expertise and Interest
steroid hormones, glucocorticoids, molecular physiology, Metabolic Diseases, Type 2 diabetes, cellular signaling, factors regulated glucose/insulin homeostasis, fatty liver
Glucocorticoids are steroid hormones that play important roles in many aspects of mammalian physiology, including metabolic adaption upon stress conditions. Because of their potent anti-inflammatory and immunomodulatory activates glucocorticoids are also frequently used to treat inflammatory and autoimmune diseases. Chronic and/or excess glucocorticoid exposure, however, causes unwanted adverse effects that limit the application of glucocorticoids and is associated with a greater risk of comorbidities. One major focus in my lab is to elucidate the mechanisms of physiological, pathological, and pharmacological effects of glucocorticoids. Glucocorticoids convey their signals through an intracellular glucocorticoid receptor (GR), which is a transcriptional regulator. We focus on identifying GR-regulated genes, such as angiopoietin-like 4 (Angptl4), that mediate glucocorticoid responses, and transcriptional coregulators, such as Ehmt2 and Ccar1, that selectively participate in physiological functions of GR. We also seek to identify signaling pathways that are specifically induced upon chronic glucocorticoid exposure. One of these pathways is ceramide- and sphingosine 1 phosphate-mediated signaling pathway. The ultimate goal is to not only advance our molecular understanding of glucocorticoid actions but also provide novel insights to design improved glucocorticoid therapy.
Genome-wide association studies (GWAS) have associated specific genetic variations to particular diseases. However, how genes containing these variations work is still largely unknown. Another focus in the lab is to identify the mechanisms underlying the actions of these GWAS genes, especially those encode transcription regulators and associate with metabolic disorders and type 2 diabetes, such as EHMT2, ZNF664 and BAHD1. Learning how these genes exert their actions could lead to the development of new therapeutic interventions against metabolic diseases.