The Wendong Huang lab uses genetically engineered mouse models and molecular pharmacology tools to identify novel signaling pathways in metabolic regulation and provide innovative targets for drug discovery. The lab primarily focuses on bile acids, bile acid receptors, and bile acid-gut microbiota crosstalk as metabolic mediators in regulating normal physiology and pathogenesis. The lab's second research focus is identifying and developing novel drug candidates, including those from natural products and other sources, to treat diabetes and cancer.

The Wendong Huang lab’s current research projects focus on

• Identification of novel signaling molecules and pathways in regulating metabolism, diabetes and cancer
• Small molecules and RNA targeted therapy for diabetes and cancer
• Mechanisms underlying bariatric surgery and diabetes therapy

Bile acid signaling and metabolic regulation 

One research focus of this lab is to investigate bile acid signaling in the gastrointestinal tract and adipose tissues, and to study its impact on obesity/diabetes, NAFLD/NASH and other diseases. Dr. Huang’s lab harnesses extensive research experience in this topic and uses a variety of approaches, including unique mouse surgical models, to evaluate the impact of bile acid signaling on metabolism. For example, the lab used mouse gastrointestinal surgery (i.e., 70% partial hepatectomy) to understand bile hormone signaling in liver regeneration and liver diseases. More recently, Dr. Huang’s lab successfully developed a mouse model of vertical sleeve gastrectomy (VSG) to understand the beneficial effects of bariatric surgery on obesity, diabetes, and fatty liver diseases. By applying these unique tools, Dr. Huang’s lab has become well-versed in the roles that bile acid signaling plays in regulating normal physiology and disease pathogenesis. The research team also found that alterations of bile acid signaling contribute to the sustained weight loss and glucose homeostasis by bariatric surgery, providing mechanistic insight into how the surgical procedure improves metabolism and ameliorate disease development. Further, bile acid receptors, including FXR, TGR5 and S1PR2, are being investigated as downstream mediators of the beneficial effects of bariatric surgery.

Nutrient sensing in the gut and host-microbiota crosstalk 

Another direction of our research lab is to understand the roles of the gut microbiota in diabetes and cancer. Gut is a primary site of nutrient sensing, which is critical in regulating lipid and glucose homeostasis. Dr. Huang’s lab is interested in understanding the molecular interactions between the host and gut microbiota, as this appears to be a critical signaling axis for systemic regulation of metabolism. For example, primary bile acids are generated in the liver but metabolized in the gut by microbiota into a large family of different bile acid species, which appears to have distinct functions in activating or suppressing the activity of bile acid receptors and other signaling pathways in host. Currently, the lab is determining the crosstalk between the host and gut microbiota in metabolic regulation, under either normal physiology or disease conditions.

Translational research and drug development

The long-term goal of this lab is to identify novel ways to treat obesity, diabetes, NAFLD/NASH, cancer and other metabolic disorders. City of Hope has excellent infrastructure and resources for drug development. Dr. Huang’s lab has identified a variety of lead compounds from either nature sources or high-through put screening. By taking advantage of the unique facilities and expertise in drug development at City of Hope, they are actively developing small molecules and RNA-targeted therapies for both diabetes and cancer. 

Dr. Huang’s lab has extensive experience training future scientists and has hosted more than 40 trainees, most of whom have become independent PIs in academia or scientists in industry. Please contact Dr. Huang directly for research training opportunities at City of Hope.