Epigenetic mechanisms—factors other than an individual’s DNA sequence—play a critical role in the regulation of gene expression and undergo routine disruption in cancer. Dr. Meier’s work focuses on the development of chemical approaches to study epigenetic signaling and its relationship to cellular metabolism. The goal of these studies is to better elucidate the underlying logic linking gene expression and metabolism, and apply this knowledge towards new approaches to cancer therapy, diagnosis, and chemoprevention.
Cofactor-Based Profiling of Chromatin Modifiers
Enzyme cofactors link cellular metabolism with the regulation of genome function through the activity of chromatin-modifying enzymes. A major focus of the laboratory is to integrate cofactor-based synthetic probes with high-throughput approaches for the proteomic, genomic, and structural characterization of chromatin modifiers. The goal of these studies is to expand the pharmacological map of epigenomic regulators involved in cancer, and to generate new knowledge for structure-based design, screening, and inhibitor development efforts.
Metabolic Regulation of Epigenetic Signaling
Recent studies have shown that many enzymes active in epigenetic mechanisms of genomic regulation are sensitive to the metabolic state of the cell. A second major aim of the lab is to understand the mechanisms by which metabolic perturbations influence genomic signaling mediated by chromatin modifying enzymes. Long term goals of this work include: 1) the discovery of biological mechanisms underlying oncometabolite-driven cancers, 2) the development of new diagnostics for cancers driven by metabolic mutations, and 3) the identification of small molecules which inhibit epigenetic modifications through metabolic disruption.
Selected Key Publications
Chemoproteomic profiling of lysine acetyltransferases highlights an expanded landscape of catalytic acetylation.J. Am. Chem. Soc. 136: 8669-76, 2014. [ Journal Article ]
- ACS Chem. Biol. 8: 2607-2621, 2013. [ Journal Article ]
- J. Am. Chem. Soc. 136: 3687-94, 2014. [ Journal Article ]
- J. Am. Chem. Soc. 134: 17814-22, 2012. [ Journal Article ]
- J. Am. Chem. Soc. 128: 12174-84, 2006. [ Journal Article ]
Dr. Meier received his undergraduate degree in chemistry from Creighton University in 2004, getting introduced to research as an National Science Foundation REU student. Following graduation he moved to the University of California-San Diego, performing graduate research in natural products biochemistry and proteomics under the mentorship of Professor Michael D. Burkart. After receiving his Ph.D. in chemistry in 2009, he moved to the California Institute of Technology. His research as an American Cancer Society postdoctoral fellow in the laboratory of Professor Peter B. Dervan focused on the development of high-throughput sequencing methods to analyze small molecule-DNA interactions. In 2013, Dr. Meier joined the NCI, where his research focuses on the development of synthetic probes to investigate metabolic and epigenetic signaling pathways in cancer.
|Arissa Bavari||Summer Student|
|Sarah Bergholtz||Postbaccalaureate Fellow|
|Chloe Briney||Postbaccalaureate Fellow|
|Rhushikesh Arun Kulkarni Ph.D.||Postdoctoral Fellow (Visiting)|
|David Montgomery Ph.D.||Postdoctoral Fellow (PRAT)|
|Jonathan Shrimp Ph.D.||Postdoctoral Fellow (CRTA)|
|Abigail Thorpe||Postbaccalaureate Fellow|
|Nicholas Vlassopoulos||Summer Student|
|Thomas Zengeya Ph.D.||Postdoctoral Fellow (Visiting)|
A Three-peat for the Meier group – FARE Awards from the NIH Research Festival
Congratulations to three post-doctoral fellows from the Meier group who were each selected to receive a FARE award for their outstanding abstracts. The Fellows Award for Research Excellence (FARE) Program is in its 21st year of providing recognition for the outstanding scientific research performed by intramural fellows who have less than five years of research experience at NIH. Sponsored by the NIH Fellows Committee (Felcom), the NIH Scientific Directors and the OITE, this annual competition selects the top 25 percent of abstracts from 53 different study sections to receive a $1,000 travel award. Winners use the travel award to present their research at a scientific meeting during the subsequent fiscal year. The FARE competition attracted more than 1,000 applicants, representing nearly a third of all eligible graduate students, postdocs and clinical fellows throughout the institutes and centers of the NIH. All submitted abstracts underwent anonymous peer-review and were scored by a panel of judges from the applicant's chosen study section. The CBL is proud to be home to three of these winners:
Jonathan Shrimp for “Microfluidic Mobility Shift Profiling of Histone Lysine Acetylation”
David Montgomery for “Chemical Proteomic Approaches to Discover and Characterize Lysine Acetyltransferase Biology”
Rhushi Kulkarni for “Profiling the Role of Non-Enzymatic Acetylation in Cancer”