The PSOC@Pennfocuses on physical changes of tissues, cells, and nuclei that contribute to cancer growth and possibly initiation. As tumors cells invade and displace normal cells, the tissue often changes physically, frequently becoming stiffer, sometimes softer, often heterogeneously. Physical changes sometimes occur even before the cancer is detectable. Primary liver cancer appears representative as it almost always arises in the setting of end-stage liver fibrosis, termed cirrhosis, with various causes including excess alcohol consumption. Liver stiffness is now being measured clinically in living patients, and initial studies already show patients with stiffer livers are far more likely to develop liver cancer within a few years.
Chromatin remodeling, DNA breaks & Cell migration: Discher group
Cells have been seen to squeeze through small gaps of matrix and other cells in many basic processes that range from immune surveillance to disease, and include invasion of cancer cellsinto nearby tissue or entry into blood capillaries. The nucleus is the largest and stiffest organelle in the cell but a cell can often push, pull, and forcibly distort this chromatin-filled organelle through a constriction. Pulling a flexible polymer into a tube is a classic problem in polymer physics, but any relevance to chromatinwithin a nucleus that is being pulled through a pore is unclear, particularly given the crowding estimated as ∼70% chromatin volume fraction. Also unclear are the effects ornot of double-strand breaksin the DNA backbone of chromatin, although such breaks—which seem to be presentatlow levels in all cells and —have been speculated to be enhanced by cell migrationthrough small pores. When cleaved DNA is stretched by optical trapsin single molecule studies, it is held together by a scaffoldof repair factors , but chromatin is made up of many other cohesion-enhancing proteins, which motivates stretching of cleaved chromatin in intact nuclei of living cells.
This summer project for an undergraduate student will focus on relations between rigidity of the cancerous tumor microenvironment and changes in the nucleus. Tumors often change mechanically, sometimes stiffening, andpotentially impacting the nucleus of invading cancer cells. The summer student will help measure various physical and other biochemical aspects of the nucleus and the DNA within