Jason Meyer Sheltzer - 01/21/2026

Jason Meyer Sheltzer
Assistant Professor of Radiation Oncology (Radiation and Cancer Biology)
 

Wednesday, January 21, 2026
3:00 - 4:00 PM  
James H. Clark Center, Room S360, 3rd floor 
 

Abstract:  

Chromosome loss events are common across tumor types but rarely occur in normal tissue, raising the possibility that these prominent alterations could be exploited as a cancer-specific therapeutic vulnerability. Here, we integrate genome-scale CRISPR screening data with chromosome-level copy number profiles to uncover dependencies that are selectively associated with individual chromosome loss events. We uncover recurrent classes of vulnerabilities that arise due to the decreased dosage of genes encoded on the lost chromosome. Notably, the most significant aneuploidy-associated dependencies uncovered by our analysis are paralogous gene pairs, in which the loss of a paralog on an aneuploid chromosome establishes a unique dependency on its redundant paralog encoded elsewhere in the genome. We apply CRISPR-based chromosome engineering to generate models of two of the most common chromosome losses in cancer: loss of the Y chromosome and loss of chromosome 8p. We demonstrate that loss of the Y chromosome, which encodes the RNA helicase DDX3Y, creates a novel dependency on its paralog DDX3X, while the loss of 8p, which encodes the phosphatase PPP2CB, creates a novel dependency on its paralog PPP2CA. Collectively, these findings provide a framework for linking recurrent karyotypic alterations with specific genetic dependencies that could be exploited for biomarker-guided therapy in aneuploid tumors.

Biography:  

Dr. Jason Sheltzer is an Assistant Professor at the Stanford University School of Medicine. The Sheltzer Lab seeks to uncover how large-scale gene dosage imbalances affect cancer physiology. Toward that goal, they apply a variety of techniques, including chromosome engineering, CRISPR screening, and single-cell sequencing, to interrogate the consequences of mitotic and meiotic chromosome segregation errors. Through this work, the Sheltzer Lab seeks to identify therapeutic strategies that can be used to selectively eliminate highly-aneuploid tumors while leaving euploid tissue unharmed.