Xia Lei

My training in medicine (M.D.) has fostered a strong interest in understanding disease pathogenesis, particularly from the perspective of molecular therapeutics. To fuel this interest, I pursued a Ph.D. in biochemistry and molecular biology, undertaking a project related to diabetic retinopathy. This work yielded important insight on the non-conventional anti-inflammatory effect of erythropoietin on Müller cells. During my subsequent brief postdoctoral training in Dr. Weijun Jin's lab at SUNY Downstate Medical Center, I demonstrated the protective effect of the furin prodomain in atherosclerosis. Through these two projects, I cemented my interest in health outcomes related to metabolic disorders. I joined Dr. Guang William Wong's lab at Johns Hopkins University School of Medicine to acquire additional skills and expertise on molecular, genetic and physiological aspects of metabolism. I have now characterized the roles of 6 of the 15C1q/TNF-Related Proteins (CTRPs) in glucose and lipid metabolism using type 2 diabetes mousemodels. I joined the Department of Biochemistry and MolecularBiology at OSU in July 2019. My lab focuses on investigating the metabolic regulation of CTRP family members in physiology and disease.

Research Interests:

C1q/TNF-Related Proteins (CTRPs) are a conserved family of 15 secreted proteins that function in glucose and lipid metabolism. Metabolism and immunity are linked by proteins with dual functions such as the CTRP family proteins. One of my postdoctoral projects focused on understanding how the CTRP6 protein links obesity to adipose tissue inflammation. In obese and diabetic humans and mouse models, I found that CTRP6 expression was markedly upregulated in adipose tissue. Mechanistically, CTRP6 regulates local inflammation and glucose metabolism by targeting adipose tissue macrophages and adipocytes, respectively. I provide the first physiological evidence, using gain- and loss-of function mouse models, that CTRP6 is a novel secreted regulator of systemic glucose metabolism through both autocrine and paracrine action, which modulates insulin sensitivity and pro-inflammatory responses within adipose tissue. My long-term goal is to understand the underlying molecular and cellular mechanisms of immunometabolic regulation by CTRPs and their receptors and other secreted proteins and their receptors. Secreted and transmembrane proteins have advanced properties that lend themselves to be utilized as therapeutic agents or targets. My lab will exploit genetic mouse models, cellular and molecular techniques, histological assays, flow cytometry, and gene expression profiling methods (e.g., RNA-seq) and metabolomics to study protein function in immunometabolism. I believe our findings will greatly contribute to the development of new potential therapeutic targets for the treatment of obesity and diabetes.