Congratulations to HAMM Lab member, Sonette Steczina, for successfully defending her Ph.D. dissertation on Tuesday, December 3, 2024!

Her dissertation was titled: “Impact of Hypertrophic Cardiomyopathy mutations on cardiac thick filament function and regulation”

Sonette has been an integral part of the HAMM Lab during her time as a graduate student and previously as an undergraduate summer volunteer student in the lab in 2015 and 2016. Her primary thesis project focused on studying a pathogenic mutation in the sarcomere protein cardiac myosin binding protein C (cMyBP- C) linked to the genetic heart disease, hypertrophic cardiomyopathy (HCM). This work illuminated both molecular and cellular mechanisms for disease pathogenesis. Sonette showed that a specific variant in cMyBP-C (MYBPC3-c.772G>A) results in incorrect transcript splicing leading to degradation and haploinsufficiency (or decreased levels) of the protein. Overall, she observed accelerated cross-bridge cycling in the sarcomere and increased recruitment of the sarcomere protein myosin, providing key insights into how a protein level mutation can lead to hypercontractility in the muscle cells of the heart.

Her work is a beautiful example of how a stem cell-derived cardiomyocyte model can be used to understand what’s going on in a patient’s heart at the molecular/cellular level that may lead to disease pathogenesis. This understanding will lead to the potential of better targeted therapeutic treatments. Sonette used a multitude of techniques and collaborations to accomplish these studies. She spent 8 months at the University of Kent in Canterbury, UK in the lab of Dr. Neil Kad to learn the technique of single molecule imaging. This technique was used to investigate changes in sarcomere thick filament regulation and energy utilization caused by two HCM linked mutations, one in cMyBP-C and one in myosin.

Her many accolades include her Ruth L. Kirschstein Predoctoral Individual National Research Service Award — F31 — from the NHLBI titled, Mechanisms of cardiomyocyte dysfunction due to the E258K-MYBPC3 mutation modeled in patient-derived cardiomyocytes. She was also previously a University of Washington ISCRM Fellow (2020-2021) and has received multiple travel awards from the Biophysical Society (2024) and one from the International Society for Heart Research – International Council (2022).

Sonette has published 1 first author and 2 additional co-author peer-reviewed manuscripts related to her graduate work with 2 more papers in the works. Her first author paper in the Journal of Molecular Cellular Cardiology (JMCC) received the Editor’s Choice Award in June 2024.

See the full article here: “MYBPC3-c.772G>A mutation results in haploinsufficiency and altered myosin cycling kinetics in a patient induced stem cell derived cardiomyocyte model of hypertrophic cardiomyopathy”

Please join us in congratulating Dr. Steczina on her momentous accomplishment! We can’t wait to see what’s next!