Peter Lewis
Credentials: PhD
Position title: Professor
Email: peter.lewis@wisc.edu
Phone: 606-263-6599
Address:
440 Henry Mall, Room 6212
Madison, WI 53706
- Lab
- Lewis Lab
Focus Groups
Cancer Biology
Education
B.S., University of Virginia
Ph.D., University of California, Berkeley
Postdoctoral Fellowship, The Rockefeller University
Research Summary
Chromatin mechanisms of transcriptional repression, epigenetic inheritance, and cancer
Research Detail
My lab investigates how disruption of chromatin-based gene regulation contributes to cancer, with a focus on diffuse midline gliomas and sarcomas. These tumors provide powerful systems for studying how misregulation of proteins involved in heterochromatin can alter cell identity, impair differentiation, and promote tumorigenesis.
A central goal of the lab is to define the molecular mechanisms that establish and maintain repressive heterochromatin states in mammalian cells. We study both facultative heterochromatin, which regulates developmental and cell identity genes, and constitutive heterochromatin, which silences repetitive and potentially destabilizing regions of the genome. Together, these systems allow us to investigate how chromatin supports normal cellular function and how its disruption contributes to disease.
A major focus of the lab is the Polycomb Repressive Complex 2, or PRC2, an epigenetic regulator that is aberrantly controlled in many human diseases. PRC2 catalyzes methylation of histone H3 lysine 27, generating H3K27me3, a chromatin modification mechanistically linked with transcriptional repression. We investigate how PRC2 is recruited to chromatin, how PRC2 catalytic activity is regulated, and how PRC2-dependent chromatin states are altered in cancer.
We also study chromatin-mediated silencing of repetitive genomic elements, including retrotransposons. This work examines how histone variants, chromatin assembly factors, and repeat-associated RNAs help recognize repetitive sequences, organize repressive chromatin, and maintain genome stability. To address these questions, we combine biochemical assays, proteomic and genomic analyses, and genetic screens in mammalian cells and patient-derived tumor cells.