Mary Kay Pflum

Mary Kay Pflum

Associate Professor

313-577-1515

313-577-8822 (fax)

pflum@chem.wayne.edu

323 Chemistry

Websites

chem.wayne.edu/pflumgroup

Mary Kay Pflum

Dr. Pflum received a B.A. degree from Carleton College working with Jerry Mohrig in physical organic chemistry. In Ph.D. training at Yale Univeristy with Alanna Schepartz, she worked on several bioorganic projects focusing on phosphoproteins and transcription factors. In an NIH post-doctoral position at Harvard University with Stuart Schreiber, she worked on chemical biology and cell biology projects focusing on histone deacetylase proteins. Dr. Pflum joined the faculty at Wayne State University in 2001 with a research program at the interface of Chemistry and Biology focusing on two cancer-related proteins - kinase and histone deacetylase enzymes.

Research Interest/Area of Expertise

  • Protein post-translational modification, histone deacetylase proteins, chemical genetics, medicinal chemistry

Research

Research in the Pflum group integrates organic synthesis, biochemistry, and cell biology to understand the molecular basis of disease. For many years, we have been particularly interested in two proteins associated with cancer formation- kinase and histone deacetylase enzymes. Our goal is to use a chemical approach to characterize the role of these proteins in cancers, which will lead to identification of novel drugs targeting these proteins and biomarkers to diagnose illness.

Our group focuses on two main projects:

I. Kinase Enzymes

Kinases catalyze protein phosphorylation, which is a ubiquitous post-translational modification that can profoundly influence protein function. However, identifying the position of phosphorylated amino acids and the physiological significance of phosphorylation has been challenging due to the paucity of available tools. We are interested in developing chemical methods to characterize kinase-catalyzed post-translational modifications.

We recently reported use of ATP analogs to label, visualize, and enrich phosphorylated proteins from protein or peptide mixtures. The method relies upon ATP analogs with a gamma-phosphate tag that can be used as a cosubstrate by kinases to label recombinant proteins and cell lysates (Figure 1). Using this strategy, we have established kinase-catalyzed biotinylation, dansylation, and crosslinking (see Green and Pflum, 2007; Green and Pflum, 2009; Suwal and Pflum, 2010, Senevirathne and Pflum, 2013, Garre, et al. 2014). We are currently focused on applying these novel labeling methods to characterize phosphoproteins in cell lysates and live cells (see Fouda and Pflum, 2015). These studies will pioneer advances in cell signaling research by coupling cell biology and biochemistry with novel synthetic ATP analogs.

II. Histone Deacetylase Enzymes
Histone Deacetylase (HDAC) proteins are transcription factors that influence cell proliferation, differentiation, and cancer formation. In fact, several small molecule inhibitors of HDAC proteins are in clinical trials to treat cancer. Unfortunately, the known drugs typically interact with eleven human HDAC proteins nonspecifically. To overcome the limitation of available drugs, we use mutagenesis to characterize the activities of histone deacetylase 1 (HDAC1) (Figure 2A, see Weerasinghe, et al. 2008). We also have a medicinal chemistry program aimed at identifying isoform selective inhibitors (Figure 2B, see Choi et al. 2011; Weerasinghe et al. 2010; Bieliauskas et al. 2007). Our goal is to expand the utility of small molecule-based HDAC inhibitors in cancer research and treatment by combining synthetic organic chemistry and cell biology.

 

Education – Degrees, Licenses, Certifications

  • B.A. Carleton College, 1992
  • Ph.D. Yale University, 1999
  • NIH Postdoctoral Fellow, Harvard University, 1999-2001

Awards and Grants

  •  Positions and Honors
    1996 Pre-doctoral Fellowship, American Chemical Society, Yale University
    1996 Pre-doctoral Fellowship, Lucille E. Dox Fellowship, Yale University
    1999 Post-doctoral Fellowship, National Institute of Health, Harvard University
    2002 Research Innovation Award, Research Corporation, Wayne State University
    2007 Teaching award, College of Liberal Arts and Science, Wayne State University
    2008 President’s Award for Excellence in Teaching, Wayne State University
    2008 Scientific Member, Barbara Ann Karmanos Cancer Institute
    2010 Career Development Chair, Wayne State University
    2012 Co-chair of the Bioorganic Chemistry Gordon Research Conference, Andover, NH
    2014 Permanent Member of the NIH SBCB study section, National Institutes of Health

    Research Funding
    National Institutes of Health (GM079529 and GM067657)
    National Science Foundation (CHE-130649)

Selected Publications

LSD1 Substrate Binding and Gene Expression Are Affected by HDAC1-Mediated Deacetylation.
Nalawansha DA and Pflum MK.
ACS Chem Biol. 2017 Jan 20;12(1):254-264. doi:10.1021/acschembio.6b00776.

K-BILDS: A Kinase Substrate Discovery Tool.
Embogama DM and Pflum MK.
Chembiochem. 2017 Jan 3;18(1):136-141. doi: 10.1002/cbic.201600

K-CLASP: A Tool to Identify Phosphosite Specific Kinases and Interacting Proteins.
Dedigama-Arachchige PM and Pflum MK.
ACS Chem Biol. 2016 Dec 16;11(12):3251-3255.

Structural Requirements of Histone Deacetylase Inhibitors: SAHA Analogs Modified on the Hydroxamic Acid.
Bieliauskas AV, Weerasinghe SV, Negmeldin AT, Pflum MK.
Arch Pharm (Weinheim). 2016 May;349(5):373-82. doi:10.1002/ardp.201500472

The generality of kinase-catalyzed biotinylation.
Senevirathne C, Embogama DM, Anthony TA, Fouda AE, Pflum MK.
Bioorg Med Chem. 2016 Jan 1;24(1):12-9. doi:10.1016/j.bmc.2015.11.029.

Courses taught

CHM 2230   Organic Chemistry II Laboratory, 1 credit hours   W2016