Faculty

Zaneta Nikolovska-Coleska

Associate Professor of Pathology
Director, Molecular and Cellular Pathology Graduate Program

Ph.D. in Pharmaceutical Chemistry, Ss. Cyril and Methodius University, Skopje, Republic of Macedonia
Post-Doctoral Fellowship in Drug Discovery, University of Michigan

Research Focus: Discovery, design and development of small molecules as new molecularly targeted therapies for cancer

Phone: 734.615.9202
E-mail: zanetan@med.umich.edu
Fax: 734.763.8764

The research focus of Nikolovska-Coleska’s group is discovery, design and development of small-molecules as new molecularly targeted therapies for cancer. Molecularly targeted therapy is a treatment that aims to interfere with the function of the biological pathway within the cancer cell that is critical to its growth or survival. By targeting a unique characteristic of the tumor, cancer cells will be specifically killed, providing effective cancer treatment with significantly fewer side effects.

We are particularly interested in targeting protein-protein interactions involved in programmed cell death and, currently, we are working on identifying small molecule inhibitors of myeloid cell leukemia-1 (Mcl-1), a potent anti-apoptotic molecule and a member of the Bcl-2 family of proteins which are central regulators of apoptosis. Mcl-1 has been found to be overexpressed in both solid and non-solid tumor cell lines and human cancer tissues. Consistent with its anti-apoptotic function, overexpression of Mcl-1 has been associated with tumor initiation, progression and resistance to current anticancer therapies. Our group is also interested in epigenetics modifications which play an important role in human cancer. Particularly we are interested in understanding protein-protein interactions that underline the histone modifications, specifically histone methylation through histone lysine methyltransferases (HKMases).

We use different strategies for identification of new hits and lead compounds, like high throughput screening, virtual screening and structure-based design. For that purpose we are developing and using series of complementary biochemical and biophysical assays, functional and cell based assays which are used for screening of compound libraries, as well as for validating and characterizing of identified small molecules. Such well-characterized small-molecules will serve as (a) pharmacological tools for elucidation and understanding of the functions of corresponding targets and (b) promising lead compounds for further optimization toward our ultimate goal of developing new anticancer drugs.

 

Awards

2003
Research Award, Department of Internal Medicine, University of Michigan
2001
International Pharmacy Initiative, Massachusetts College of Pharmacy and Health Sciences (Boston)
2000 Chemical Structures Association (CSA) Trust Award
1999
Certificate of Merit, Amersham Pharmacia Biotech & Science Prize for Young Scientists


Representative Publications

  1. Nikolovska-Coleska, Z., Meagher, J.L., Jiang, S., Kawamoto, S.A., Gao, W., Yi, H., Qin, D., Roller, P.P., Stuckey, J.A., and Wang, S., "Design and Characterization of Bivalent Smac-based Peptides as Antagonists of XIAP and Development of a Fluorescence-Polarization Assay for XIAP containing both BIR2 and BIR3 domains", Anal. Biochem., 2008, 374, 87-98.

  2. Nikolovska-Coleska, Z., Meagher, J.L., Jiang, S., Yang, C.Y., Qiu, S., Roller, P.P., Stuckey, J.A., and Wang, S., "Interaction of a Cyclic, Bivalent Smac Mimetic with the X-linked Inhibitor of Apoptosis Protein", Biochemistry, 2008, 47, 9811-9824.

  3. Zhang, B., Nikolovska-Coleska, Z., Zhang, Y., Bai, L., Qiu, S., Yang, C.Y., Sun, H., Wang, S., and Wu, Y., "Design, Synthesis and Evaluation of Tricyclic, Conformationally Constrained Small-Molecule Mimetics of Second Mitochondria-derived Activator of Caspases", J. Med. Chem., 2008, 51, 7352-7355.

  4. Sun, H., Nikolovska-Coleska, Z., Lu, J., Meagher, J.L., Yang, C.Y., Qiu, S., Tomita, Y., Ueda, Y., Jiang, S., Krajewski, K., Roller, P.P., Stuckey, J.A., and Wang, S., "Design, Synthesis, and Characterization of a potent, Nonpeptide, Cell-Permeable, Bivalent Smac Mimetic That Concurrently Targets both the BIR2 and BIR3 Domains in XIAP", J. Am. Chem. Soc., 2007, 129, 15279-15294.

  5. Wang, G., Nikolovska-Coleska, Z., Yang, C.Y., Wang, R., Tang, G., Guo, J., Shangary, S., Qiu, S., Gao, W., Yang, D., Meagher, J., Stuckey, J., Krajewski, K., Jiang, S., Roller, P.P., Abaan, H.O., Tomita, Y., and Wang, S., "Structure-based design of potent small-molecule inhibitors of anti-apoptotic Bcl-2 proteins", J. Med. Chem., 2006, 49, 6139-6142.

  6. Nikolovska-Coleska, Z., Hu, Z., Xu, L., Tommita, Y., Li, P., Roller, P., Wang, R., Fang, X., Lippman, E.M., Zhang, M., Yang, D., and Wang, S., "Discovery of Embelin as A Cell-Permeable, Small-Molecular weight inhibitor of XIAP through Structure-based Computational Screening of Traditional Herbal Medicine Three-Dimensional Structural Database", J. Med. Chem., 2004, 47, 2430-2440.

  7. Nikolovska-Coleska, Z., Wang, R., Fang, X., Pan, H., Tomita, Y., Li, P., Roller, P.P., Krajewski, K., Saito, N., Stuckey, J., and Wang, S., "Develoment and Optimization of a Binding Assay for the XIAP BIR3 Domain using Fluorescence Polarization", Anal. Biochem., 2004, 332, 261-273.

 

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