Anny Lam, a senior pharmacological chemistry major at the University of California San Diego, investigated the functional association between a drug candidate and CARHSP1 in cancer cell lines.
Despite new advances in therapeutics such as chemotherapy and immunotherapy, cancer remains one of the top leading causes of death in the United States. Spending my summer at the Broad was a life-changing experience. When I first joined, I was afraid I was not capable enough to be a scientist and that led me to think research was probably not right for me. However, by the end of BSRP 2022, I had cast those doubts aside with the support of an amazing community and the meaningful relationships I formed. This experience renewed my passion for science as I felt empowered to grow as a leader, honed my science communication skills and became more confident while having fun doing research. I am grateful to have had this incredible opportunity and am excited to move forward on my journey with this clarity.The prominence of this disease has pushed for efforts to identify novel compounds for therapy. Those efforts include PRISM technology, which allows for a high-throughput approach to phenotypic viability screening by pooling cell lines and deconvoluting their response to small molecules using unique integrated DNA barcodes. Recent studies using the PRISM assay to screen thousands of compounds against hundreds of cancer cell lines identified a novel small molecule with potent and selective activity against cell lines with particularly high expression levels of CARHSP1. Drug selective cytotoxicity is especially striking as only 10 out of 770 cell lines were found to be sensitive. Interestingly, CARHSP1 was found to be required for drug sensitivity in a genome-wide CRISPR knockout resistance screen. The primary objective of the project was to further elucidate if CARHSP1 functions as a rheostat determining drug cytotoxicity. To investigate the functional association with the drug, CARHSP1 was overexpressed and knocked out in cancer cell lines. Results suggest that the drug candidate was more potent in cell lines that overexpressed CARHSP1 compared to the gene knockout cell lines, which were more resistant. Our findings suggest this small molecule may be a new therapeutic opportunity for cancers with high CARHSP1 expression.
Project: PRISM Identifies a Drug Candidate as a CARHSP1-Selective Molecule
Mentor: Tiffany Tsang, PRISM Lab, Cancer Program