11/16/2021
By Susan Pryputniewicz

The Biomedical Engineering and Biotechnology program invites you to attend a doctoral dissertation defense by SaiLavanyaa Sundar on “The Tropomyosin Overlap Domain: Fine Tuning Mechanisms in Muscle Regulation and Cardiomyopathy.”

Name: SaiLavanyaa Sundar
Date: Tuesday, Nov. 30, 2021
Time: 11 a.m. to 2 p.m.
Location: Room 503, Olsen Hall, North Campus

Committee Chair (Advisor): Jeffrey Moore, Ph.D., Professor, Department of Biological Sciences, University of Massachusetts Lowell

Committee Members:

  • Matthew Nugent, Ph.D., Associate Dean for Research, Innovation and Partnerships, Professor, Department of Biological Sciences, University of Massachusetts Lowell
  • Matthew Gage, Ph.D., Associate Professor, Department of Chemistry, University of Massachusetts Lowell
  • Nicolai Konow, Ph.D., Assistant Professor, Department of Biological Sciences, University of Massachusetts Lowell

Abstract:
Dilated cardiomyopathy (DCM), a disease affecting 1 in 250 individuals, widely remains undiagnosed till onset of severe symptoms that often lead to heart failure. DCM is the leading cause for heart transplantation in the US and Europe. Human genome sequencing and genetic testing of DCM patients have identified at least 12 missense mutations in the thin filament regulatory protein, alpha-tropomyosin (Tpm; encoded by TPM1 gene). However, the exact mechanism for how these mutations lead to DCM is unknown and information about the initial stages of the disease and its effects on muscle regulation are scarce.

Here, this dissertation focuses on characterizing the biochemical, structural, and functional effects of alterations in the Tpm end-end overlap domain, that is known to be important for Tpm’s stability and regulatory function in calcium-mediated thin filament activation. Our studies provide important insights into structure – function relationships in the biochemical mechanisms of Tpm’s regulatory function and have highlighted molecular level modulations that fine-tune Tpm interactions with other thin filament proteins, further revealing critical aspects that help identify and validate targets as potential therapeutic interventions to disease.

All interested students and faculty members are invited to attend the defense.