Peter W. Lewis

Associate Professor, Department of Biomolecular Chemistry Lab Website 263-6599

4214A HF DeLuca Biochemical Sciences Building
440 Henry Mall
Madison WI 53706-1535


B.S., University of Virginia
Ph.D., University of California, Berkeley
Postdoctoral, The Rockefeller University

Chromatin dynamics in cancer

Biochemistry of Chromatin-modifying Proteins
My research program is rooted in the idea that eukaryotic chromatin, the physiologically relevant form of genomes, contains an indexing system that represents a fundamental regulatory mechanism. Covalent modifications to both DNA and histone proteins allow chromatin to act as a dynamic information hub that integrates diverse biochemical stimuli to regulate genomic DNA access and ultimately establish and maintain cellular identity.

Aberrant chromatin regulation, as a consequence of mutation or abnormal signaling is associated with many diseases, especially cancer. The identification of oncogenic mutations has led to the emerging view of “driver mutations” in chromatin regulators underlying many human cancers. My research is aimed at defining how changes in chromatin structure aids in the establishment and maintenance of gene expression programs involved in normal development and tumorigenesis.

Ongoing research in the laboratory is directed at describing the molecular mechanisms by which histone H3 mutations drive tumorigenesis, and how the variant histone H3.3 functions in the maintenance of genome integrity in mammals.

Peter Lewis graphical abstract
A remarkably high frequency of specific tumor types harbor monoallelic, gain-of-function mutations in genes encoding histone H3 (collectively referred to as ‘oncohistones’). We use a combination of biochemical approaches, cell models, and human tumor samples to comprehensively understand how H3 mutations drive tumorigenesis. Our studies have led to identification and characterization of a novel oncoprotein called EZHIP, which mimics the biochemical mechanism of “H3 K27M oncohistone” in gliomas. Model for mechanism of K27M/EZHIP: We demonstrated that the K27M mutant histone and EZHIP inhibit the activity of allosterically activated PRC2. Changes in H3K27me3 levels by the oncoproteins likely promotes tumorigenesis through aberrant gene silencing.

Photo of Peter Lewis

Areas of Expertise

  • Biomolecular Folding & Interactions
  • DNA Metabolism & Genome Maintenance
  • Gene Expression & RNA Biology
  • Quantitative Biology