Dennis E. Discher
University of Pennsyvania, Philadelphia, PA
Mechanoregulated gene expression is of course epigenetic and has been clear for decades. Extensive clinical data across many cancers motivates experiments that now show the DNA sequence in a cell is also altered by mechanical factors, including 3D matrix rigidity and actomyosin forces. Solid tumors are also replete with macrophages, and mechanisms to entice them to engulf cells in such tumors pose a mechanical as well as molecular challenge. Cooperative interactions of these immune cells help disrupt solid tumors for cancer cell engulfment, and in vivo cures based on the approach can initiate a vaccination response with anti-tumor antibodies. The approach could complement efforts with Tcell-targeting tumor vaccines.
BIO
The Discher lab has sought to discover, explain, and exploit the mechanobiology of cells, molecules, and tissues. Early discoveries included matrix elasticity effects on stem cell differentiation (Cell 2006) and mechanoregulation of the nucleus (Science 2013). Current efforts focus on physics-driven evolution of mutations (Cell 2016) and tumoricidal macrophages (Nat BME 2023) informed by molecular studies of ‘foreign’ versus ‘self’ (Science 2013). Trainees from the lab are leaders in academia and industry around the world. Honors include election to the US National Academy of Medicine, the US National Academy of Engineering, and the US Academy of Arts & Sciences. Service includes Editorial Boards of Science and PNAS Nexus among other journals.