From Max-Delbrück_center, Berlin (DEU)

will give a seminar entitled :

Cellular mechanics of heart development and regeneration

Abstract

Organs form through precise coordination between cell proliferation, cell fate specification, and differentiation. Physiological cues, such as mechanical forces, have been increasingly implicated in organ formation and homeostasis, yet how they integrate with developmental signaling remains incompletely understood. A long-standing interest of my lab is to understand the interactions between physiological cues and Wnt signaling, a major signaling pathway in development.

The heart is the first functional organ to form during vertebrate development, which cells (cardiomyocytes) are capable of spontaneous and synchronized electrical activity followed by force-generating contractions. Additionally, adult zebrafish heart can regenerate after damage. Using zebrafish heart as a paradigm, we investigate both quantitative and qualitative aspects of interactions between physiological cues and Wnt signaling as the heart develops as well as in cardiac regeneration. In our previous work, we have established the genetic, cellular, mechanical and functionalheterogeneities that emerge as the heart chambers form. We have uncovered Wnt signaling as the key pathway driving these features in developing cardiomyocytes.

My ongoing and future research focuses on the role of mechanical stimuli during cardiovascular development in zebrafish and on studying their impact in the context of heart disease modeling, regeneration, and tissue repair. Combining novel transgenic zebrafish tools with multi-disciplinary approaches including quantitative imaging and single-cell omics, we aim to understand the cellular mechanics at multiple levels: i) at the cardiac progenitor level, by analyzing the integration of cellular and mechanical dynamics in early heart formation through Wnt signaling ii) at the subcellular level, by identifying how Wnt signaling impacts gene expression through modulation of nuclear mechanics, iii) at the level of regenerating tissue, by determining cell-level responses in healthy and regenerating hearts and their interplay with mechanical cues and Wnt signals.

Our findings promise to reveal new insights into molecular mechanisms of human diseases that integrate the functional inputs and that are affected in congenital heart disease, arrhythmias, cardiac hypertrophy, and heart failure.