My work at Upenn mainly focuses on the correlation between nuclear envelope rupture and DNA damage. The genomic heterogeneity within a tumor is increasingly recognized as important in understanding cancer progression and drug resistance. Recent studies show a possible causality of this genomic heterogeneity is nuclear envelope rupture which occurs when cancer cells migrate through constrictions created by the dense extracellular matrix. We found that when lamin-A, a structural protein in the nucleus, is partially depleted in 2D conventional culture, the nucleus becomes softer and more susceptible to stress-induced rupture. After rupture, loss of multiple repair factors are observed and this mis-localization of repair factors is sufficient to cause DNA damage. The observation we saw can help to understand the mechanism that 3D constricted migration can cause nuclear envelop rupture and DNA damage. We are now attempting to understand how stress ruptures the envelope inside the constriction and trying different methods to rescue DNA damage caused by envelope rupture.
Mr. Xia currently works in the Discher Lab.