My laboratory uses molecular biological and genomic approaches to study hormonal regulation of transcription, particularly thyroid hormone (TH). We study whether epigenetic changes such as DNA methylation and histone modifications play a role in positive and negative regulation of transcription, endocrine tumors, long-term suppression of negative feedback by TH, and hormone-responsiveness during aging. Recently, we have shown that TH regulates Fox01 via SIRT deacetylation to regulate gluconeogenic genes, and we currently are studying this novel regulatory mechanism in greater detail. We also examine the potential beneficial effects and mechanisms of TH on non-alcoholic fatty liver disease (NAFLD), a common complication of obesity and diabetes.
My laboratory’s recent discovery that TH as well as other hormones and compounds such as caffeine and epigallocatechin-3-gallate (EGCG) can induce autophagy coupled with increased b-oxidation of fatty acid has suggested novel potential therapeutic strategies for this condition. I also have initiated a clinical study examining whether levothyroxine can ameliorate hepatosteatosis and glucose control in diabetic Asian patients in patients with NAFLD. I have collaborated with Dr. Dwight Koeberl, Duke University for the past two years to examine the role of autophagy in the hepatosteatosis and hepatic glycogen storage in G6Pase deficiency. We have found that there is defective autophagy, impaired beta oxidation of fatty acids, and mitochondrial injury and dysfunction in G6Pase deficiency suggesting that correction of the autophagy defect can improve the major hepatic metabolic dysfunctions in this disease.