02/13/2024
By Irma Silva

The Kennedy College of Sciences, Department of Biological Sciences, invites you to attend a master’s thesis proposal defense by Alfredo Bongiorno, entitled "The Role of Key Tropomyosin-Troponin T Interactions in Thin Filament Mediated Myocardial Regulation."

Candidate: Alfredo Bongiorno
Date: Tuesday, Feb. 27, 2024
Time: 1 to 3:30 p.m.
Location: Olsen 403

Committee members:

  • Jeffrey Moore, Professor, Biological Sciences, University of Massachusetts Lowell
  • Teresa Lee, Assist. Professor, Biological Sciences, University of Massachusetts Lowell
  • Matthew Gage, Assoc. Professor, Chemistry, University of Massachusetts Lowell

Title: The Role of Key Tropomyosin-Troponin T Interactions in Thin Filament Mediated Myocardial Regulation.

Abstract:
Approximately three in every 500 individuals are born with hypertrophic cardiomyopathy (HCM) or dilated cardiomyopathy (DCM), dominant genetic conditions arising from disruptions in intracellular calcium regulation within the heart muscle. HCM manifests as impaired relaxation during ventricular filling at low calcium levels, while DCM results from impaired contraction during ventricular emptying at high calcium levels (i.e., diastolic and systolic dysfunction for HCM and DCM, respectively). Mutations in genes encoding myocardial contractile proteins, particularly thin filament (TF) regulatory proteins, are involved in both conditions. The cardiac TF, governing contraction by sensing intracellular calcium levels, undergoes conformational changes at a threshold of pCa 6, enabling myosin-actin cross bridge cycling. Notably, mutations in genes encoding Actin, Troponin (Tn), and Tropomyosin (Tpm) within the cardiac TF, especially TnT, have been linked to disease. Despite TnT being a "hot spot" for disease-linked mutations, detailed residue-specific information about TnT-Tpm interactions and their impact on heart muscle function remains unknown. This study aims to investigate the contributions of crucial Tpm-TnT interactions in cardiac muscle regulation by calcium, seeking to enhance our understanding of the molecular mechanisms underlying mutation-induced diseases. This knowledge is crucial for developing targeted therapies addressing the molecular basis of both HCM and DCM, potentially preventing eventual irreversible compensatory remodeling of the myocardium.