The major goal of my research program is to advance our understanding of the epigenetic and transcriptional regulation of metabolic processes and to identify potential targets for therapeutic intervention in metabolic disorders such as obesity and type 2 diabetes. A major focus of my lab has been on the study the function and gain mechanistic insight of epigenetic modifiers in adipose and skeletal muscle biology and whole-body metabolism in disease and health. To achieve the goal, my lab employs multiple approaches including mouse genetics, molecular and cellular biology, and global profiling studies.
We identify a small molecular weight of Jumonji domain-containing protein, whose expression is increased in insulin resistant mouse models including diet and genetic mous models of insulin resistance. Moreover, the expression of this protein is suppressed by feeding and insulin. We then noted that the expression of this protein is most abundant in adipose tissue relative to other tissues and that it is enriched in adipocytes compared to stromal vascular fraction of cells. Such expression pattern led us to explore its role in the regulation of adipose insulin sensitivity. Our in vitro studies demonstrate that mouse and human adipocytes lacking this gene are more insulin sensitive while adipocytes with its overexpression are more insulin resistant. Consistent with these results, the whole-body knock-out mice exhibit improved insulin sensitivity and glucose tolerance even on chow diet and more apparently on high fat diet. Conversely, adipose-specific Jmjd8 transgenic mice exhibit an impaired insulin sensitivity when challenged by high fat diet. Mechanistically, we identify that the function of this protein is wired into the transcriptional regulation of proinflammatory genes in adipocytes in a cell autonomous manner. Future direction: We will firmly determine the metabolic functions of this protein in adipose tissue by conducting in-depth metabolic characterization of the KO and TG mice, including in vivo insulin signaling. Moreover, we are in the process of generating Jmjd8 floxed mice to ascertain the adipose-specific function for this protein in metabolism. Our current data suggest that this protein exclusively reside in the cytosol and lose the ability to suppress inflammation when enforced to be in the nucleus. Additional mechanistic studies are underway to understand the mechanisms whereby this protein regulates insulin sensitivity and inflammation.
This is continuation of previous SPUR project.
Undergraduate researchers from SPUR program are expected to participate virtual lab meetings and present research articles for weekly journal clubs, or participate in in-person research.