Page 39 - Rappaport Institute Magazine 2024

GENETICS AND DEVELOPMENTAL BIOLOGY
36-37
Dissecting the interactions between cells and the ECM in health and disease
My lab is interested in the interactions that take place between the extracellular matrix (ECM) and the distinct cell types within the skeletal, cardiac and vascular muscles, tissues rich in ECM where many human diseases that affect them are ECM-related. We concentrate on embryonic development and adult homeostasis. Specifically, we focus on the roles played by members of the lysyl oxidase (LOX) family, a family of enzymes that regulates ECM maturation in otherwise normal scenarios but also in multiple pathologies. It is now clear that members of this family not only participate in ECM maturation, as once thought, but rather are implicated in a plethora of other unrelated processes. We further use several model systems to dissect how connective tissue resident cells develop, participate in stress-induced ECM remodeling, and how can we use our knowledge and expertise in this field to develop new therapeutic approaches for related pathologies focusing on fibrotic diseases. Our work combines in- vivo experiments, mouse genetics, cell cultures, and computational tools for bioinformatics and images analysis.
Selected Publications
ˆ Melamed S, et al., Initiation of fibronectin fibrillogenesis is an enzyme-dependent process. Cell Reports 2023.
ˆ Yaseen-Badarneh W, et al., Fibroblast fusion to the muscle fiber regulates myotendinous junction formation. Nature Communications 2021.
ˆ Gabay Yehezkely R, et al., Intracellular role for the matrix modifying enzyme Lox in regulating transcription factor subcellular localization and activity in muscle regeneration. Developmental Cell, 2020
Research Support:
ˆ 2022-2024 – M2LOX-inhib a novel drug aimed at reducing the fibrotic burden in DMD. ADI Foundation. Peleg Hasson (P.I.).
ˆ 2023 – Inhibiting enzyme-mediated fibronectin fibrillogenesis as a novel strategy for blocking fibrosis. Rappaport Foundation Translational Grant. Hasson P (P.I.) and Wolfenson H (co-P.I.).
ˆ 2023 – Inhibiting enzyme-mediated fibronectin fibrillogenesis as a novel strategy for blocking fibrosis. T-start Hasson P (P.I.) and Wolfenson H (co-P.I.).
ˆ 2023-2027 – Fibroblasts diversification in the embryonic skeletal muscle. Israel Science Foundation. Peleg Hasson (P.I.).
phasson@technion.ac.il
Peleg Hasson Lab
Peleg Hasson, PhD Associate Professorof Cell and Developmental Biology
PhD 2005 – The Hebrew University of Jerusalem, Israel
Deletion of Lox in smooth muscle cells attenuates cardiac remodeling in response to hypertension. Wheat germ agglutinin (WGA) and picro
sirius red, stainings of extracellular matrix, demonstrate that in response to hypertension, hearts become fibrotic (left), but not if Lox is deleted in smooth muscle cells (right).