HER2 is a member of human epidermal growth receptors (EGFR/HER) family proteins. Overexpression of HER2 is found in ~25% of breast tumors and is generally associated with poor patient survival. Although there are different small-molecule tyrosine kinase inhibitors (TKIs) and anti-HER2 antibodies therapies that have been developed which showed relative clinical success, tumors frequently develop resistance and patient relapse. Recent studies found that the major cause of treatment failure in HER2 directed therapies is due to the drug-induced compensatory upregulation of HER3 (another member of HER family protein). Though HER3 is critical in early development (embryonic lethal in knockout mice) and expressed at very low levels in adult tissues such as skin and colon, yet it is commonly activated in many cancer types like breast, colorectal, and gastric cancer. My work is to understand how HER3 function in physiologic signaling and how this function is perturbed in cancer cells.