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Pranav Ganapathy

CA ID: 14088607
Colon cancer is one of the deadliest and most prevalent epithelial cancers in the world. In
most cancers like colon cancer, metastasis of the tumor is the critical step in the proliferation and
spread of the disease. Previous research suggests that muscarinic receptors such as M3R in colon
cancer take an active role in aiding with metastasis and could hold the key to therapy of the
disease. Various agonists like acetycholine activate signaling complexes in M3R that produce
various matrix metalloproteinases, or MMPs. The attributes of MMP1, a protein that breaks
down collagen and thus allows the cancer to metastasize, are in special focus in this study. In
order to establish the role of agonists in MMP1 production, acetylcholine, EGF, and EGF+PMA
were added to a cell plate with HT29 colon cancer cells that had a scratch through the middle of
the plate. After antiproliferative agent mitomycin C was added, the cells were grown for 24 hours
and photographed with an Axiovert microscope. After a computer program calculated mean
migration in arbitrary units, it was established that ACh, EGF, and EGF + PMA contributed to
increases in migration from the control with no serum. Next, various inhibitors of the agonists of
MMP1 production including acetylcholine, PKC isozyme, EGFR, MEK, Src, and p38MAPK
were added along acetylcholine. After a similar procedure followed, it was established that the
p38MAPK inhibitor produced a decrease of over 80 units of migration from the control. A
further trial only with p38 inhibitor and acetylcholine confirmed its ability to mitigate colon
cancer metastasis. The identification of the p38 mitogen-activated protein kinase as an area of
interest for colon cancer therapy has huge implications for the pharmaceutical industry and the
treatment of other epithelial cancers.

Description of Involvement:
This project on colon cancer metastasis was undertaken at the University of Maryland Medical
Center during the months of July and August 2014. I specifically worked with plating and
scratching the cells, adding serum and agents to the plates, as well as taking pictures under the
microscope. I could unfortunately not access the computer programs as a student, but I
synthesized and analyzed the data my mentor provided me from the program. This project earned
the 2015 MIT Alumni Award for High School Science Research. This past summer at Johns
Hopkins University, I learned many techniques including animal dissections, PCR, genotyping,
gel electrophoresis, blood processing, and spectrophotometry with my research on Crohn’s. I
specifically worked to analyze the role of the CLC5 gene in Crohn’s disease and am currently
working with my mentor to publish a literature review on the effectiveness of azathioprine in
Crohn’s treatments.