Diego Valdes Cavazos

Diego, a sophomore studying Biomedical Engineering at the University of Texas at San Antonio, established a cancer cell model to study the regulatory mechanisms for α-synuclein in Parkinson’s disease.

Parkinson's disease (PD) is an age-related neurodegenerative disease affecting motor and cognitive function. I am incredibly grateful to the Broad for providing me with an enriching platform that not only deepened my knowledge in previously unexplored topics but also improved me as a researcher and individual. The nurturing and innovative environment at the Broad provided seamlessly merged research and collaboration to create transformative discoveries. Through the BSRP, I experienced an accelerated course that, coupled with fantastic guidance from its dedicated educators, transformed me into a better scientist and leader. Additionally, the bonds and friendships I forged with my cohort throughout my research are invaluable connections I will hold dearly. Thank you to the Broad for a transformative summer that showed I can do anything. PD pathology is characterized by progressive cell death of dopaminergic neurons in the substantia nigra and aggregation of alpha-synuclein (SNCA) that forms Lewy bodies. Multiple genomic studies established that SNCA is a major PD driver; however, the natural cellular role and the pathways regulating SNCA-mediated cell death are still poorly characterized. The ability to use commonly utilized genomic screening approaches to reveal SNCA regulating mechanisms is undermined by the inability to culture physiologically relevant dopaminergic neurons to enable genetic screening, and other more ‘screenable’ cell lines do not exhibit SNCA-induced growth phenotypes as observed in PD. We aim to use an unbiased high throughput approach and a targeted one to explore which cancer cells exhibit cell growth inhibition and death upon the over-expression of the A53T mutant form of SNCA. First, we will overexpress A53T SNCA in 500 cancer cell lines and explore the effect on viability across multiple time points. Second, we will focus on neuroblastoma and melanoma cancer cells that share specific pathways with dopaminergic neurons and naturally express SNCA. Preliminary findings suggest that A53T mutant SNCA overexpression can induce growth defects in a subset of cancer cell lines. Ultimately, establishing a cell line model with a robust viability phenotype will enable us to initiate whole genome and chemical screens to find new regulators of SNCA.

Project: Establishing a cell model to enable high-throughput chemical genomic studies to reveal mechanisms regulating alpha-synuclein in Parkinson’s Disease.

Mentors: Peter Tsvetkov & Rishi Puram

PI: Golub Lab, Cancer Program