Engineering Tissue Mechanics to Control Genome Integrity

Abstract

Cells sense and respond to mechanical cues in their microenvironment, and these physical signals play a central role in regulating cell behavior and tissue organization across development and disease. Notably, many tissues that undergo extensive mechanical remodeling also exhibit recurrent changes in genome content. However, engineered tissue culture systems that enable causal tests of how mechanics regulates the genome remain limited. In this seminar, I will present recent work demonstrating that extracellular matrix stiffness and physical confinement disrupt the fidelity of cell division and chromosome segregation in engineered tumor tissues, leading to genomic changes that result in tumor heterogeneity. I will then show how migration through physically confined tumors reveals a distinct, mechanically enabled strategy by which immune cells invade and engulf cancer cells. Together, these studies highlight how the mechanical microenvironment regulates genome stability and motivate a mechanogenetics framework for studying hormone-responsive tissues relevant to women’s health.

Biography

Alisya Anlas is an AAAS Science and Technology Policy Fellow at the U.S. National Science Foundation. She received her Ph.D. in Chemical and Biological Engineering from Princeton University and completed her postdoctoral studies at the University of Pennsylvania. In her research, Alisya uses engineered tissue culture models to uncover how the mechanical properties of the tissue microenvironment regulate hallmarks of cancer such as sustained proliferation, survival, genomic instability, and immune evasion. Her work spans engineering, biology, and policy, with a particular interest in employing mechanobiology approaches to advance women’s health.