Shenhav Cohen

PhD (Direct track): Faculty of life sciences, Bar Ilan University, 2002

MSc: BSc: Faculty of life sciences, Bar Ilan University, 1996

Nano Main Field: Nanostructure and dynamics of filamentous assemblies within striated muscles in pathological catabolic states. We use biochemical, genomic and bioinformatic approaches, as well as an electron microscopy to characterize the subcellular organization and structural properties of the desmin cytoskeleton in disease, and the effect of its depolymerization on the integrity of the fundamental contractile machinery in muscle, the myofibrils. The combination of these powerful techniques together with the development of in vitro assembly regimes will increase our understanding of muscle architecture in health and disease.

Research Interests: we study the molecular mechanisms of myofibril destruction during atrophy induced by inactivity or disease. Myofibrils comprise the majority of muscle proteins and are responsible for force production. Upon disuse, denervation or aging, and in systemic catabolic states, including cancer cachexia, diabetes and sepsis, myofibril destruction is accelerated leading to muscle wasting, disability, morbidity and mortality. The integrity of myofibrils is likely to be compromised by the initial destruction of certain myofibril stabilizing structures, hence facilitating their degradation by different enzymes and the proteasome. We focus on the distinct individual proteolytic steps that lead to myofibril loss during rapid or slow atrophy, and specifically on the structural changes of filamentous assemblies, whose loss accelerates myofibril destruction. We use an electron microscopy, genomic and bioinformatic approaches to acquire nano-resolution of these critical structures, and to determine the molecular mechanisms leading to their disassembly during atrophy. Our goal is to identify critical key players in this debilitating process of atrophy in order to facilitate the development of new rational therapies.