Page 38 - Rappaport Institute Magazine 2024

Modulating cellular response to matrix rigidity. (A) Top: Cells activate apoptosis on soft matrices through phosphorylated YAP (pYAP) at adhesions. Bottom: Suppressing cellular forces by Blebbistatin (Bleb) results in adhesion growth, reduced pYAP, and decreased apoptosis. (B) Number of large focal adhesions (FAs) in the absence or presence
of 5μM Bleb. (C) % apoptotic cells in the absence or presence of 5μM Bleb.
GENETICS AND DEVELOPMENTAL BIOLOGY
Haguy Wolfenson, PhD Associate Professor of Mechanobiology
PhD, 2012 – Tel Aviv University, Israel
Studying principles of mechano-biology of cells in health and disease
My laboratory studies basic aspects of cellular mechano-biology, namely, the mechanisms by which cells receive information about the mechanical properties of their environment and the ways in which these properties affect cellular behaviors. In particular, we are interested in mechanisms of rigidity sensing since the rigidity of the extracellular matrix is a critical regulator of many cellular functions. Moreover, we are interested in understanding how irregular mechanical signals or defective cellular responses to mechanical signals are involved in medical disorders, including cancer and fibrosis.
In the past few years, we have made significant progress in understanding how cells test the rigidity of the extracellular matrix and how this affects cellular functions such as growth, apoptosis, and migration. We also identified ways by which cells modulate the extracellular matrix to control their fates, and we are currently following up on these findings to develop treatments for fibrotic diseases.
Selected Publications
ˆ Feld, L, Kellerman L, Mukherjee A, Livne A, Bouchbinder E & Wolfenson H. Cellular contractile forces are nonmechanosensitive. Science Advances, 2020. 6: eaaz6997. doi:10.1126/sciadv.aaz6997. Recommended by Faculty Opinions
ˆ Mukherjee A, Melamed S, Damouny-Khoury H, Amer M, Feld L, Nadjar-Boger E, Sheetz MP & Wolfenson H. a-Catenin links integrin adhesions to F-actin to regulate ECM mechanosensing and rigidity dependence. Journal of Cell Biology, 2022. 221: e202102121. doi: doi.org/10.1083/jcb.202102121
ˆ Melamed S, Zaffryar-Eilot S, Nadjar-Boger E, Aviram R, Zhao H, Yaseen-Badarne W, Kalev-Altman R, Sela-Donenfeld D, Lewinson O, Astrof S, Hasson P & Wolfenson H. Initiation of fibronectin fibrillogenesis is an enzyme dependent process. Cell Reports, 2023. 42: 112473. doi: 10.1016/j.celrep.2023.112473
ˆ Shi L, Nadjar-Boger E, Jafarinia H, Carlier A & Wolfenson H. YAP mediates apoptosis through failed integrin adhesion reinforcement. Cell Reports, 2024. 43: 113811. doi: 10.1016/j.celrep.2024.113811.
Grants and Awards
2017-2021 – Israel Science Foundation, The role of a-catenin in epithelial-to- mesenchymal transition
2022-2025 – John Templeton Foundation, Cells as the basic units of biotic purposive behavior: from active sensing to decision making
2023-2026 – DFG, German Research Foundation, Deciphering the role of mechanotransduction in biomineralization during sea urchin skeletogenesis 2023-2024 – T-Start Science Accelerator, Inhibiting enzyme-mediated fibronectin fibrillogenesis as a novel strategy for blocking idiopathic pulmonary fibrosis Aurélie Carlier, Maastricht University
Ben Goult, University of Liverpool
Michael Sheetz, The University of Texas Medical Branch
haguyw@technion.ac.il
Haguy Wolfenson Lab