Brian G. Rowan, PhD

Post-translational modifications of estrogen receptor-α(ERα) in physiology and disease

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Our research focuses on understanding the role of post-translational modifications of estrogen receptor alpha (ERα), particularly phosphorylation, in physiology and disease. We demonstrated that targeted disruption of specific phosphorylation sites in ERα results in altered breast tumor growth and response to endocrine therapy. We are currently evaluating the role of ERα phosphorylation in mouse physiologic processes and development. Using a knock-in approach in mice, we demonstrated that mutation of a serine phosphorylation site to alanine in mice (S216A) resulted in delayed mammary gland development, reduced fertility and early onset of mortality in both male and female mice. Our ongoing work with S216A mice and another knock-in model, S171A mice, has demonstrated a tissue specific role for ERα phosphorylation in mice. These collective studies will provide the groundwork for rational design of agents that block or activate specific kinase signaling pathways that alter ERα phosphorylation to impact physiological processes.