Structure and function of epigenetic reader domains



Profile

Dr. Glass obtained her B.S. in Microbiology from the University of Massachusetts, Amherst, MA in 1999. She then gained her Ph.D. in Microbiology & Molecular Genetics from UVM in 2005 before becoming a Postdoctoral Researcher at the University of California, Santa Cruz, CA with Dr. Harry Noller (2005-2006). After her California postdoc, she worked as a NIH Postdoctoral Fellow at University of Colorado, Denver, CO with Dr. Tatiana Kutateladze (2006-2010) before coming to the Albany College of Pharmacy and Health Sciences as an Assistant Professor in Pharmaceutical Science in 2010. In 2011, she became an Adjunct Assistant Professor in Biochemistry at UVM and recently joined the CMB program faculty.

Research Description

The human genome is compacted into chromatin, allowing nearly three meters of DNA to fit into the small volume of the nucleus. Chromatin is composed of DNA and histone proteins, and this DNA-protein complex is the template for a number of essential cellular processes. For example, DNA transcription, replication and repair are regulated by the spatial organization of chromatin throughout the cell cycle, which can be manipulated by chromatin remodelers that alter specific chemical modifications on the histones and DNA. Understanding the role of chromatin remodeling proteins in transcriptional control is important as deregulation of gene expression (due to mutation or overexpression) can contribute to disease progression.

The Glass laboratory investigates how epigenetic mechanisms regulate diverse cellular activities. High field Nuclear Magnetic Resonance (NMR) spectroscopy, X-ray crystallography, and biochemical and molecular biology approaches are utilized determine the three-dimensional structures and functions of chromatin binding proteins implicated in human diseases such as leukemia, heart disease and cancer. Ultimately, these studies will lead to the identification of new therapeutic targets, more specific treatment strategies, and better overall outcomes for patients.

The current focus of the lab is to:

1) Determine the role of the BRPF1 bromodomain in regulating the MOZ histone acetyltransferase in leukemogenesis.
2) Characterize how MOZ interacts with RUNX1 in live cells to carry out its function, and identify genes it controls in normal blood cell development versus in the diseased state.
3) Establish how ING PHD finger domains interact specifically with the unmodified and modified histone H3 tail, and understand how mutations in these tumor suppressor proteins are linked to cancer.

Highlighted Publications

Lubula MY, Eckenroth BE, Carlson S, Poplawski A, Chruszcz M, and Glass KC (2014) Structural insights into recognition of acetylated histone ligands by the BRPF1 bromodomain. FEBS Lett, Accepted for publication on 9/16/14.

Hassan HE, Carlson S, Abdallah I, Buttolph T, Glass KC, Fandy TE. (2014) Curcumin and Dimethoxycurcumin Induced Epigenetic Changes in Leukemia Cells. Pharm Res, epub ahead of print. PMID: 25186441

Lubula M, Poplawski A and Glass KC (2014) Crystallization and preliminary X-ray diffraction analysis of the BRPF1 bromodomain in complex with its H2AK5ac and H4K12ac histone peptide ligands. Acta Cryst. F70, doi:10.1107/S2053230X14018433

Carlson S and Glass KC. (2014) The MOZ Histone Acetyltransferase in Epigenetic Signaling and Disease. J. Cell. Physiol. Nov;229(11):1571-4. doi: 10.1002/jcp.24617. [Epub ahead of print]. PMID: 24633655

Poplawski A, Hu K, Lee W, Natesan S, Peng D, Carlson S, Shi X, Balaz S, Markley JL, Glass KC. (2014) Molecular Insights into the Recognition of N-Terminal Histone Modifications by the BRPF1 Bromodomain. J Mol Biol 426: 1661-1676. PMID: 24333487

Lalonde ME, Glass KC, Avakumov N, Joncas FH, Saksouk N, Paquet E, Holliday M, Tan S, Yang XJ, Kutateladze TG and Côté J. (2013) Exchange of associated factors directs a switch in HBO1 acetyltransferase histone tail specificity. Genes Dev. Sep 15;27(18):2009-24. PMID: 24065767

* indicates equal contribution


Karen Glass, Ph.D.

Karen
Glass, Ph.D.

Assistant Professor
Department of Biochemistry

 

802-735-2636
Office: 302G ACPHS VT Campus
Lab: Third Floor ACPHS VT Campus

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