Dennis Discher

Soft-physics biology and how physical forces shape cell fate and function

Abstract:

Mechanoregulation of gene expression is now well-established and extends to matrix elasticity effects on stem cell differentiation (Cell 2006) as well as mechanosensing by a cell’s nucleus (Science 2013). The latter observation led us to consider fat which is usually considered soft, but the phase-separated fat droplets accumulate within cells and remain round as they displace and deform organelles – even causing rupture of the nucleus at sites of high curvature (J Cell Biol 2023). Transient loss of multiple DNA repair factors into the cytoplasm increases DNA damage and triggers a cell cycle checkpoint. The findings illustrate our more general efforts addressing whether DNA sequence in a cell is altered by various physical factors, with evidence of matrix stiffness effects in clinical data across many cancers. A better understanding of mutation processes is timely for immunotherapies – especially for challenging solid tumors. 

Speaker: Dennis E. Discher, Ph.D., University of Pennsyvania, Philadelphia, PA

The Discher lab has sought to discover, elucidate, and even exploit physical contributions to cell, molecular and tissue function. Early discoveries included matrix elasticity effects on stem cell differentiation (Cell 2006) and mechanosensing by a cell’s nucleus (Science 2013). Current efforts focus on physical determinants of genetic instability and 
heritable mutations (Cell 2016) as well as engineering of macrophages to attack solid tumors and initiate immunity (Nat BME 2023). The latter followed molecularly detailed studies of ‘foreign’ versus ‘self’ recognition (Science 2013). Dozens of trainees from the lab have secured positions in academia and industry around the world. Honors include election to the US National Academy of Medicine, the US National Academy of Engineering, the American Academy of Arts and Sciences, Fellow of the American Association for the Advancement of Science and the American Society for Cell Biology. Service has included numerous NIH Study Sections as well as Editorial Boards of Science, Molecular Biology of the Cell, and PNAS Nexus among other journals.

Host: Sergei Sukharev

Seminars start at 4:00 pm, and refreshments will be served at 3:45 pm. All seminars are held in the 2136 Physical Sciences Complex (#415) unless otherwise noted.