The role of TIPE0 and its regulation of GasderminC in intestinal epithelial cell proliferation and pyroptosis.

Ryan holding test tubes in a lab.

Students

College

Faculty

Professor of Pathology and Laboratory Medicine

Project Summary

Goals

My research this summer was conducted under the guidance of Dr. Jason Goldsmith and Dr.  Youhai Chen in the Chen Laboratory in Penn Medicine’s Department of Pathology and Laboratory Medicine.  The goal of my project was to investigate the role of TNFα-induced protein eight (TIPE0) in cell growth and cell death. We’ve seen that the intestines of mice that lack TIPE0 and cells that have much less TIPE0 than normal grow faster than those that have TIPE0.  However, we’ve also seen that TIPE0 knockout intestinal cells (those that don’t have TIPE0) are more prone to death in chronic injury (bacterial infection and a model of inflammation in the colon).  We think that this might be due to an increase in levels of a protein called Gasdermin C (GSDMC) in TIPE0 knockout cells and my goal over the summer was to figure out how TIPE0 and GsdmC relate to each other.

Results

After confirming that the cells we had edited using CRISPR/Cas9 had less TIPE0 than normal we used a scratch assay to investigate wound healing (which involves cell growth). In the experiment we scratch a line into a sheet of cells in a plate and track how fast the cells grow back into the scratch.  We found that the cells that have less TIPE0 grew back into the scratch more rapidly than those that had normal levels of TIPE0. We also found through other experimental methods that TIPE0 likely binds to GSDMC which could be a way in which TIPE0 interacts with GSDMC. 

Experience

I have worked at Chen Lab since my freshman fall and the experience has been enlightening and enriching in more ways than I could possibly describe here.  Working over the summer was an amazing experience last summer and working here over the summer again was just as fulfilling as I expected it would be. I’ve already gotten so much experience doing wet lab research and I look forward to continue doing, both throughout university and hopefully as a career.  I went into this research position very skeptical but I learned that I genuinely enjoy it, and in all honesty, I think that’s the most important thing I’ve gained from this lab.  As my mentor Dr. Chen always tells his undergrads: either way, whether you like it or not, regardless of what project you work on or what skills you gain, you’ve learned something from the experience of working in a wet lab; you’ve learned something about yourself. Aside from the explorative nature of it, the lab that I worked in offered me a lot of really amazing opportunities to learn both the techniques used in research as well as the thought processes that are involved in planning and analyzing experiments.