RESEARCH

The long-term goal of our research is to elucidate mechanisms underlying regulation of metabolic homeostasis. Metabolic disorders are associated with various diseases, such as diabetes, fatty liver diseases, and cancer. Our current studies encompass fundamental investigation of physiological processes and novel approaches to therapeutic intervention. The lab focuses on a single regulatory pathway, glucocorticoid signaling, applying a combinatorial approach, including biochemistry, genetics, chemistry and physiology, to dissect its function in metabolic regulation. Glucocorticoids are steroid hormones that play important roles in many aspects of mammalian physiology, including metabolic adaptions under stress conditions. Because of their potent anti-inflammatory and immunomodulatory activities, 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 are associated with a greater risk of comorbidities. Glucocorticoids convey their signals through an intracellular glucocorticoid receptor (GR), which is a transcriptional regulator. We focus on identifying GR-regulated genes that mediate glucocorticoid responses, and transcriptional coregulators that selectively participate in the physiological and pharmacological functions of GR. We also seek to identify signaling pathways that are specifically induced upon chronic glucocorticoid exposure. The goal is not only to advance our molecular understanding of glucocorticoid actions, but also to provide novel insights in designing improved glucocorticoid therapy.

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Genome-wide association studies (GWAS) have associated specific genetic variations to diseases. However, how genes containing these variations exert their actions are largely unknown. Another focus in the lab is to identify the mechanisms underlying the actions of these GWAS genes, especially those that encode transcriptional regulators and associate with metabolic disorders and type 2 diabetes. Learning how these genes exert their actions could lead to the development of new therapeutic interventions against metabolic diseases.