Associate Professor
Research Areas
Cancer gene regulation
Research Interests
Our laboratory focuses on the development of peptide and small-molecule inhibitors of cell signaling proteins involved in cancer gene regulation and apoptosis resistance. We utilize a multidisciplinary approach employing nuclear magnetic resonance spectroscopy (NMR) structural biology, synthetic peptide chemistry, NMR and cell based high-throughput drug screening, peptide phage display screening, pharmacophore identification, and cell biology studies to better understand key mechanisms amenable to anti-cancer therapeutic development. A focus of the lab is to develop peptides that mimic one part of key protein-protein interactions for use in target validation and to quickly and specifically target key biological processes.
A central focus of the lab is the study of the anti-apoptotic Bcl-2 family, MCL-1. MCL-1 protein levels have been identified as a key determinant for tumor response and resistance to taxane, vinca-alkaloid, and platinum-containing chemotherapeutics. Therefore, understanding how MCL-1 is regulated and how it influences DNA damage response is critical in assessing how best to deploy multiple classes of emerging targeted therapeutics aimed at the Bcl-2 family, MCL-1 directly, or at proteins that regulate MCL-1 expression and stability.
Key projects currently being pursued in the lab are:
- Characterizing the impact that reverse BH3 (rBH3)-containing proteins have on regulation of the anti-apoptotic Bcl-2 family proteins, especially MCL-1.
- Determining the post-transcriptional regulators of the anti-apoptotic Bcl-2 family protein MCL-1.
- Utilizing mutants of the SUMO E2 ligase, Ubc9, to study the structural determinants of SUMO target selection.
- Developing high-throughput screening assays for use in anti-cancer therapeutic development.
Currently, our research is funded by the NIH and the Alabama Drug Discovery Alliance.
Education
Graduate School
Ph.D., The Scripps Research Institute, La Jolla, CA
Postdoctoral Fellowship
Sanford-Burnham Medical Research Institute
Contact
Office
Shelby Biomedical Research Building
Room 710
1825 University Blvd.
Birmingham, AL 35294-2182
Phone
(205) 975-2465
Email
placzek@uab.edu