Assistant Professor in Biomolecular Chemistry, Epigenetics
Wisconsin Institute for Discovery
Research Interests:DNA Metabolism & Genome Maintenance; Developmental Biology; Gene Expression & RNA Biology
Epigenetic Mechanisms in Development and Cancer
The human genome is estimated to contain ~20,000 unique genes, and although every gene exists within every cell of the body, only a small fraction of genes are activated in any given cell type. The establishment of cell type-specific gene expression patterns helps define cell identity during differentiation and development. In order to preserve cell identity, lineage-specific gene expression must be maintained, and failure to stably silence genes normally expressed in other lineages has the potential to cause developmental defects or promote diseases such as cancer.
My research program is rooted in the idea that chromatin, the physiologically relevant form of eukaryotic genomes, contains an indexing system, sometimes referred to as a “histone or epigenetic code”, that represents a fundamental regulatory mechanism that operates outside of the DNA sequence itself. Covalent modifications to DNA and histones – the proteins that package our genome – are implicated in the epigenetic regulation of gene expression and the stable maintenance of cell type-specific gene expression patterns and cellular identity.
- Brown ZZ, Muller MM, Kong H, Lewis PW, Muir TW
Targeted Histone Peptides: Insights into the Spatial Regulation of the Methyltransferase PRC2 by using a Surrogate of Heterotypic Chromatin
Angewandte Chemie 2015 May 26;53(22):6457-61
- Jayaram H*, Hoelper D*, Jain SU, Canton N, Lundgren SM, Poy F, Allis CD, Cummings R, Bellon S, Lewis PW.
S-adenosyl methionine is necessary for inhibition of the methyltransferase G9a by the lysine-9-to-methionine mutation on histone H3.
Proc Natl Acad Sci. 2016 May 31;113(22):6182-7
- Lu C, Jain SU, Hoelper D, Bechet D, Molden RC, Ran L, Murphy D, Venneti S, Hameed M, Pawel BR, Wunder JS, Dickson BC, Lundgren SM, Jani KS, DeJay N, Papillon S, Andrulis IL, Sawyer SL, Grynspan D, Turcotte RE, Nadaf J, Fahiminiyah S, Muir TW, Majewski J, Thompson CB, Chi P, Garcia BA, Allis CD, Jabado N, Lewis PW.
Histone H3K36 mutations promote sarcomagenesis through altered histone methylation landscape
Science. 2016 May 13;352(6287):844-9
- Paul PK, Rabaglia ME, Wang CY, Stapleton DS, Leng N, Kendziorski C, Lewis PW, Keller, MP, Attie AD.
Histone Chaperone ASF1B Promotes Human ß-cell proliferation via Recruitment of Histone H3.3 Cell Cycle. 2016 Oct
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