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Samantha Harris, Ph.D.

Samantha Harris, Ph.D.

Stop making waves: A new regulatory role for cardiac myosin binding protein-C in contraction

When

October 11, 2019, 11:00 a.m. to 12:00 p.m.

Who

Samantha Harris, Ph.D.

Professor
Cellular and Molecular Medicine
University of Arizona

Where

Fralin Biomedical Research Institute, R3012
2 Riverside Circle, Roanoke, VA 24016

Cardiac myosin binding protein-C (cMyBP-C) is a critical regulator of heart muscle contraction that is phosphorylated by adrenergic stimuli (“fight-or-flight” responses), whereas mutations in MYBPC3, the gene encoding cMyBP-C, are the most frequent cause of hypertrophic cardiomyopathy (HCM). However, the mechanisms by which cMyBP-C affects cardiac contraction are complex and only partly understood. A primary obstacle has been the lack of methods to rapidly modify cMyBP-C at its position in sarcomeres in situ. To overcome this obstacle, we designed a novel hybrid genetic/protein engineering approach to efficiently “cut and paste” cMyBP-C at its native location in sarcomeres. Results using this new method showed that loss of cMyBP-C (“cut”) caused sustained auto-oscillatory contractions when detergent permeabilized myocytes were activated by submaximal [Ca2+]. Ligation (“paste”) of new recombinant cMyBP-C abolished the oscillations, but phosphorylated cMyBP-C did not. These results suggest a previously unrecognized role of cMyBP-C in damping sarcomere-generated contractile waves in a phosphorylation dependent manner.

This Pioneers in Biomedical Research Seminar is presented by the Fralin Biomedical Research Institute and co-sponsored by the institute's Center for Heart and Reparative Medicine Research.

Additional Details

This is a free event. The host is Fralin Biomedical Research Institute Center for Heart and Reparative Medicine Research. For more information, please call 540-526-2002, or send an e-mail.

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