CANCELLED: Frontiers of Science: Prof. Jason Sheltzer
Prof. Jason Sheltzer, Yale School of Medicine, USA
Mischaracterized anti-cancer agents and their true targets
Host: Jukka Westermarck (email@example.com)
The Sheltzer Lab studies the genetic changes that drive cancer progression and cause developmental disabilities. The group is particularly interested in a condition called aneuploidy – a state in which cells gain or lose whole chromosomes. Aneuploidy is found in more than 90% of human tumors and is the most common cause of miscarriage and intellectual disability, but its effects on cell physiology are poorly understood. We apply a variety of complementary technologies, including chromosome engineering, CRISPR/Cas9 mutagenesis, and single cell sequencing, in order to develop new ways to model aneuploidy and to better understand its cellular and organismal consequences. The genetic alterations that occur during tumorigenesis re-wire the underlying architecture of cancer cells and create certain cancer “dependencies”: genes and pathways that are required for cancer cell growth but that are dispensable in normal tissue. Drugs that inhibit the function of a cancer dependency can serve as potent therapeutic agents. Using CRISPR/Cas9, the Sheltzer Lab is working to identify novel cancer dependencies, and to improve the characterization of the drugs that target them.
Schukken KM, Sheltzer JM. 2022. Extensive protein dosage compensation in aneuploid human cancers. Genome Res. 32:1254-1270
Smith JC, Sheltzer JM. 2022. Genome-wide identification and analysis of prognostic features in human cancers. Cell Rep. 38:110569
Chen WC, Zhou J, Sheltzer JM, Kinney JB, McCandlish DM. 2021. Field-theoretic density estimation for biological sequence space with applications to 5′ splice site diversity and aneuploidy in cancer. Proc Natl Acad Sci U S A. 118:e2025782118
Vasudevan A, Schukken KM, Sausville EL, Girish V, Adebambo OA, Sheltzer JM. 2021. Aneuploidy as a promoter and suppressor of malignant growth. Nat Rev Cancer. 21:89-103
Lin A, Sheltzer JM. 2020. Discovering and validating cancer genetic dependencies: approaches and pitfalls. Nat Rev Genet. 21:671-682
Smith JC, Sheltzer JM. 2018. Systematic identification of mutations and copy number alterations associated with cancer patient prognosis. Elife. 7:e39217
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