TCRC Seminar Series | Modulation of cardiac inflammation and fibrosis by the Hippo-Yap pathway

The University of Arizona College of Medicine – Phoenix's Translational Cardiovascular Research Center Seminar Series presents the following lecture:

Abstract:
Inflammation and fibrosis are hallmarks of heart disease independent of etiology and are thought to contribute to impaired cardiac dysfunction and the development of heart failure. However, the underlying mechanisms that regulate these processes remain incompletely defined. As a result, effective treatments to mitigate excessive inflammatory responses and fibrosis are lacking. The Hippo-Yap signaling pathway is a fundamental and evolutionarily conserved kinase cascade that regulates multiple cellular functions including growth, proliferation and survival. Our initial studies focused on the role of this pathway in cardiomyocyte demonstrated critical roles in modulating hypertrophy and apoptosis in ischemic injury and heart failure. However, as this pathway has emerged as a potentially attractive therapeutic target for mitigating cardiac pathology, we have focused our more recent investigations to determine Hippo-Yap function in non-myocytes within the heart including cardiac fibroblasts and immune cell populations. This ongoing work has uncovered striking cell-type specific functions that mediate distinct and sometimes opposing cardiac outcomes. Taken together, these findings implicate Hippo-Yap as an important molecular nodal point that facilitates cardiac inflammation and fibrosis during heart stress and suggest that selective pathway inhibition may prove a novel therapeutic target for cardiovascular disease.

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Dominic Del Re, PhD
Associate Professor, Department of Cell Biology & Molecular Medicine
Rutgers New Jersey Medical School

Del Re earned his doctorate from the University of California, San Diego, with Joan Heller Brown, PhD, chair of the Department of Pharmacology, investigating the role of the small G-protein RhoA in modulating cardiomyocyte growth and survival in cardiac ischemic injury. Del Re completed his postdoc training in the lab of Junichi Sadoshima, MD, PhD, chair of Cell Biology and Molecular Medicine at Rutgers New Jersey Medical School. As a postdoc fellow, Del Re investigated the role of the Hippo signaling pathway in the development of heart failure, with a specific focus on upstream regulation of key Hippo pathway components during myocardial stress. Del Re is interested in elucidating novel signaling pathways that mediate heart injury, remodeling and failure following ischemic stress. Projects in the lab focus on Hippo signaling in multiple cardiac cell types, with the goal of better understanding how the heart responds to stress.

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