A. Burger
Angelika Burger, Ph.D.
Professor
Wayne State University
Karmanos Cancer Institute
Hudson Webber Cancer Research Ctr
4100 John R. Street, Room 640.2
Detroit, MI 48201

(313)576-8302 (office)
(313)576-8248 (lab)
(313)576-9417 (fax)

Email: burgera@karmanos.org

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.

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.

Burger Fig 2

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 Rani Kona, Ph.D. (Postdoctoral Fellow)
Megan Stojcevski (Laboratory Manager)
Daniela Buac (Research Assistant)
Nicole Nechiporchik (Research Assistant)
Bradley Burcz (Research Assistant)
Karri Stark (Student Assistant)
George Ventro (Student Assistant, Honors Program)
Sachin Gupta, M.D. (Clinical Oncology Fellow)
Patrick Nolan (Undergraduate Summer Cancer Biology Research Fellow)

Publications

Burger, A.M., Amemiya Y., Kitching, R., Seth, A.K. Novel RING E3 Ubiquitin Ligases in Breast Cancer. Neoplasia 8:689-95, 2006

Phatak, P., Cookson J.C., Dai F., Smith,V., Gartenhaus, R.B., Stevens, M.F.G., Burger, A.M.. Telomere Uncapping by the G-Qadruplex Ligand RHPS4 Inhibits Clonogenic Tumour Cell Growth In Vitro and In Vivo Consistent with a Cancer Stem Cell Targeting Mechanism. Br. J. Cancer 96:1223-33, 2007.

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.

Patents:

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