Research interests
Research in our lab aims to understand how post-translational modifications of proteins direct epigenetic and cellular signaling pathways to regulate key biological functions, including the establishment of proper states of gene expression and the ability of cells to respond to stress. Histones, the primary protein component of chromatin, are subject to many types of post-translational modification, including acetylation, phosphorylation and methylation. These modifications are critical to controlling the accessibility of DNA during essential processes such as transcription and DNA repair.
We are specifically interested in methylation of histone lysine residues, a modification system that has been well-established to regulate chromatin structure and function. Aberrant regulation of histone lysine methylation leads to the disruption of chromatin homeostasis and has been implicated in numerous human pathologies, including tumorigenesis. There remain many unanswered questions regarding the functional and mechanistic details of both canonical and novel sites of histone methylation. Additionally, the existence of non-histone protein methylation is emerging as a key regulator of nuclear signaling pathways, but the extent and function of these methylation events are largely unknown.
Our primary research objectives are to (1) identify new mechanisms of chromatin regulation mediated by novel histone methylation events and (2) develop a comprehensive understanding of lysine methylation as a broad regulator of nuclear signaling pathways. We use budding yeast as a model system, integrating molecular biology, genetics, biochemistry, genomics and proteomics. The evolutionary conservation of many of the players involved in lysine methylation signaling allows our work to be broadly applicable to higher eukaryotes, and will provide insight in to the role of these factors in diverse human diseases.
Education
- , Molecular Biology — Stanford University (2013)
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Ph D, Molecular and Cell Biology
— University of California, Berkeley (2007) The dynamic nucleus: Chromatin structure and the regulation of gene expression
- BA, Biology — Bryn Mawr College (2000)
Publications
- Regulatory Roles for SIRT1 in Aging and Immunosenescence 2025
- Defining biological and biochemical functions of noncanonical SET domain proteins 2024
- The SMYD3-MAP3K2 signaling axis promotes tumor aggressiveness and metastasis in prostate cancer. 2023
- Set1 regulates telomere function via H3K4 methylation-dependent and -independent pathways and calibrates the abundance of telomere maintenance factors 2023
- Using yeast to define the regulatory role of protein methylation. 2020
- Function of the MYND Domain and C-Terminal Region in Regulating the Subcellular Localization and Catalytic Activity of the SMYD Family Lysine Methyltransferase Set5. 2020
- SET domains and stress: uncovering new functions for yeast Set4. 2019
- Histone Modifications and the Maintenance of Telomere Integrity. 2019
- Assessing Yeast Cell Survival Following Hydrogen Peroxide Exposure. 2019
- Set4 is a chromatin-associated protein, promotes survival during oxidative stress, and regulates stress response genes in yeast. 2018
- Chromatin Immunoprecipitation (ChIP) of Histone Modifications from Saccharomyces cerevisiae. 2017
- Repression of Middle Sporulation Genes in Saccharomyces cerevisiae by the Sum1-Rfm1-Hst1 Complex Is Maintained by Set1 and H3K4 Methylation. 2017
- Choose Your Own Adventure: The Role of Histone Modifications in Yeast Cell Fate. 2017
- The histone methyltransferases Set5 and Set1 have overlapping functions in gene silencing and telomere maintenance. 2017
- Set5 and Set1 cooperate to repress gene expression at telomeres and retrotransposons. 2014
- Proteome-wide enrichment of proteins modified by lysine methylation. 2014
- New marks on the block: Set5 methylates H4 lysines 5, 8 and 12. 2012
- A negative feedback loop at the nuclear periphery regulates GAL gene expression. 2012
- Methylation of H4 lysines 5, 8 and 12 by yeast Set5 calibrates chromatin stress responses. 2012
- Overlapping regulation of CenH3 localization and histone H3 turnover by CAF-1 and HIR proteins in Saccharomyces cerevisiae. 2011
- Members of the H3K4 trimethylation complex regulate lifespan in a germline-dependent manner in C. elegans. 2010
- Replication-independent histone deposition by the HIR complex and Asf1. 2005
Grants and Contracts
- Leveraging human iPSC models for mechanistic investigation of chromatin regulators linked to rare neurodevelopmental disorders 2025
- The SMYD lysine methyltransferase Set6 in proteostasis and signaling 2023
- The SMYD lysine methyltransferase Set6 in proteostasis and signaling 2019
- Lysine methylation at chromatin and cellular responses to stress 2017
- Mechanisms of chromatin homeostasis at telomeres mediated by histone lysine methyltransferases 2016
- Lysine methylation at chromatin and cellular responses to stress
- The SMYD lysine methyltransferase Set6 in proteostasis and signaling
Research in Progress
- Investigating the impact of dysregulated MLL5 in epigenetic processes and gene expression in neurodevelopment using human iPSCs 2025
- Lysine methylation signaling and stress responses 2013
Courses Taught
- Cell Biology
- Appr To Molecular Biol