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Angelika Burger, Ph.D.
Wayne State University |
RESEARCH INTERESTS:
Dr. Burger’s research focus is the identification and validation of new molecular targets and molecularly targeted agents for the treatment of cancer. Her particular interest is in the ubiquitin-proteasome pathway in breast cancer and the design and evaluation of ubiquitin E3 ligase inhibitory agents. In particular, the lab is investigating the role of the RING-finger ubiquitin E3 ligase BCA2 in the regulation of Rab-mediated endocytic trafficking of oncogenic receptor tyrosine kinases such as epidermal growth factor receptor (EGFR). Other aspects of this project are the interaction and co-regulation of BCA2 with estrogen receptor (ER). Inhibitors of BCA2 have been identified and are being directed toward ejecting zinc ions from the catalytic site in the RING-finger domain, as well as toward the E2 interacting domain of BCA2.
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Fig.1. A. Model of the BCA2 monomeric RING-finger (purple) ubiquitin E3 ligase; binding to Rab7 (orange) and the E2 conjugating enzyme UbcH5 (pink). B. RING H2 domain model, showing position of Zn2+ ions (magenta), cysteine (sulfur) residues (yellow) and histidine residues (blue). |
Other research areas include cancer stem cells, and the development of telomerase inhibitors as cancer stem cell-directed treatments. Dr. Burger’s lab has been involved in developing a new class of telomerase inhibitory agents, termed telomere targeting agents (TTAs), for which she was recognized with the Science Prize for Translational Research by the German Cancer Society in 2005.
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Fig.2. A. Interphase and metaphase telomere staining (pink) in PC3 prostate cancer cells. B. Telomere targeting by KML001 causes rapid telomere erosion, leading to telomeric DNA damage signaling and cell death (From Clin. Cancer Res. 14: 4593-4602, 2008). |
Dr. Burger is the author of over 100 original articles, reviews or book chapters, and editorial board member of Clinical Cancer Research, European Journal of Cancer, British Journal of Cancer, Journal of Chemotherapy, and Cancer Genomics and Proteomics. She is also the current chairman of the European Organization for Research and Treatment (EORTC) and National Cancer Institute (NCI, US) Drug Discovery Committee.
Current Lab Personnel:Fathima R. Kona (Post Doctoral Fellow)
Silke Suer (Research Associate)
Nicole Nechiporchik (Research Assistant)
Sudha Govind (Research Assistant)
Karri Stark (Student Assistant)
Luke Bisoski (Medical student research assistant)
Kristin Lieb (Medical student research assistant)
Lauren Marquette (Medical student research assistant)
Ryan Stevens (Lab Manager)
Publications
Phatak, P., Burger, A.M. Telomerase and Its Potential for Therapeutic Intervention. Br. J. Pharmacol.152:1003-11, 2007
Chumsri, S., Burger, A.M. Cancer stem cell targeted agents: Therapeutic approaches and consequences. Curr. Opin. Mol. Ther.10:323-333, 2008.
Phatak, P., Dai, F., Nandakumar, M.P., Gutierrez, P.L., Edelman, M.J., Hendriks, H., Burger, A.M. KML001 (sodium meta arsenite) cytotoxic activity is associated with its binding to telomeric sequences and telomere erosion in prostate cancer cells. Clin. Cancer Res 14: 4593-4602, 2008.
Smith, V., Dai, F., Spitz, M., Peters, G.J., Fiebig, H.H., Hussain, A., Burger, A.M. Telomerase activity and telomere length in human tumor cells with acquired resistance to anticancer agents. J. Chemother. 21: 542-9, 2009.
Nakanishi, T., Chumsri, S., Khakpour, N., Brodie, A.H., Ross, D.D., Burger, A.M. Side-population cells in luminal-type breast cancer have tumour-initiating cell properties, and are regulated by HER2 expression and signaling. Br. J. Cancer. 102: 815-26, 2010.
Patents:
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Burger A.M. Telomere Targeting Agents as Stem Cells Directed Treatments. US Patent No. 12/118,394 (May 11, 2008). Patent
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Burger A.M., Hendriks H., Rademaker B. Methods and compositions for treatment of cancer. WO/2009/120697 (01.10.2009). Patent
Search PubMed for publications from the Burger Lab.
