Research Topics

Endocrinology, Metabolic Regulation, Regulation of Gene Expression

Disease Research Interests

Cancer, Metabolic Disorders/Diabetes

Bachelors in Pharmacy, Birla Institute of Technology & Sciences, Pilani, India
MSc, Birla Institute of Technology & Sciences, Pilani, India (Biological Sciences)
Ph.D., University of Texas, Graduate School of Biomedical Sciences at Houston (Biochemistry)
Postdoctoral Fellow, Baylor College of Medicine, Houston

Liver metabolism in normal and diseased state

My laboratory will focus on understanding liver metabolism in normal and diseased state. Our goal is to investigate how bile acids and nuclear receptors maintain metabolic homeostasis, and contribute to liver diseases, including cancer using cell-based systems and genetically engineered mouse models.

Liver is a major organ that regulates metabolism of triglycerides, cholesterol, glucose, amino acids, heme, xenobiotics and many more substances. One of the salient features of the liver is to make bile! Bile acids are amphiphilic detergents synthesized in liver to facilitate absorption of dietary lipids. Biliary homeostasis is critical and defects/dysfunctions in this pathway lead to several liver diseases including liver cancer.

Nuclear receptor signaling regulates biliary homeostasis.

Bile acid concentrations are tightly maintained through a negative feedback mechanisms coordinated chiefly by nuclear receptors, Farnesoid X Receptor (FXR) and Small Heterodimer Partner (SHP). We generated global FXR; SHP double knockout (DKO) mice to understand the consequence of biliary overload. These DKO mice have chronically elevated bile acids and mimic pediatric cholestasis.

We next want to examine the tissue specific role for FXR and SHP. Is the coordinate role of FXR and SHP observed in liver maintained in other tissues as well? How does tissue specific loss of these two receptors affect synthesis, transport and recirculation of bile acids?

Nuclear receptor signaling regulates adipogenesis

Obesity and diabetes have emerged as major epidemics of the 21st century. More than 100 genes have now been identified for their role in regulating body fat. These genes are controlled by multiple signals, including nuclear receptors and bile acids (BAs).

Our findings indicate that elevated BAs protect against obesity. It is fascinating that naïve mice on a BA enriched diet as well as DKO mice, which have elevated BAs, exhibit decreased visceral fat without any difference in food intake. We want to understand how BAs and nuclear receptors, especially FXR and SHP, regulate this beneficial effect. Do they burn more fat? Are they more active? Do they have defective adipogenesis?

Bile acids signal to Hippo pathway and cause hepatocellular carcinoma (HCC)

HCC is the fifth most common malignancy and results in 500,000 deaths annually. The underlying molecular events leading to HCC are still being evaluated and no targeted drug therapy currently exists for HCC.

Hippo signaling has been recently identified as a regulator of organ size and as a critical contributing factor to the development of spontaneous HCC. Bile acids are known to promote liver tumors and we recently identified BAs as regulators of hippo pathway. Consistent with this, the DKO mice, which have excess amounts of BAs develop rigorous and spontaneous HCC. We are excited to examine the importance of BA mediated YAP activation in liver tumorigenesis. How do BAs signal to the hippo pathway? Is it direct or mediated via other signaling proteins? Is there any nuclear receptor involved in this process?

Overall, these projects will broaden our understanding of bile acid signaling and nuclear receptor-mediated pathways necessary in the maintenance of energy balance, regulation of hepatic metabolism, and protection from tumorigenesis.

2020 - Listed in "Teachers Ranked as Excellent"
2016 - Outstanding Advisor Award, Medical Scholars Program, UIUC, IL