Margaret Westfall

Margaret Westfall, Ph.D.

Associate Professor of Cardiac Surgery
Accepting new students?
No
Research Interests:
Cardiac myocyte; Sarcomere; Post-translational Modifications; Protein kinase

I welcome a diverse workplace in my laboratory. I believe inclusion of diversity is critical for the success and advancement of research and education at the University of Michigan. Members of my laboratory are encouraged to pursue research and educational opportunities to promote diversity, equity and inclusion.

My laboratory investigates the significant impact of thin filament post-translational modifications on cardiac performance and progressive dysfunction. My PhD training was in organ systems physiology, while post-doctoral work defined developmental troponin I isoform transitions and functional domains within cardiac troponin I (cTnI). As an independent investigator, my laboratory initially focused on viral-mediated gene transfer to gain insights into the role cTnI phosphorylation plays in modulating contractile function in isolated human and rodent myocytes and in vivo models of heart failure. A current focus of my laboratory is on the contribution protein kinase C (PKC)-targeted cTnI phosphorylation plays in cardiac dysfunction. Our recent work shows PKC-targeted cTnIS43/45 reduces both systolic and diastolic function in myocytes, and chronic phosphorylation of this cluster causes heart failure. Our most recent data shows that sustained modification at cTnIS43/45 communicates sarcomere stress to mitochondria, which initiates early oxidative stress, altered energetics and mitochondrial remodeling. An important goal of the currently funded NIH grant tests whether these primary and secondary responses contributes to progressive heart failure in a mouse model. A functionally conservative substitution for this cluster also was developed, which is essential for phospho-null studies. Our analysis includes the sarcomere structure, in vivo and cellular contractile function and remodeling, plus mitochondrial structure and function.