Research excellence transforming patient care
Chiayeng Wang, PhD
Our current research focuses on fusion transcription factor family of proteins that result from chromosomal translocation and their role in cancer development. The working model understudy is Rhabdomyosarcomas (RMS). RMS tumors are the most common soft-tissue sarcoma of childhood cancer. RMS tumors are a heterogeneous group of malignant skeletal muscle tumors with alveolar RMS (aRMS) as the most aggressive. Greater than 85% of aRMS is characterized by either one of the two unique chromosomal translocations, t(2;13)(q35;q14) and t(1;13)(q36;q14) resulting in the formation of PAX3-FKHR and PAX7-FKHR fusion transcription factors, respectively. The fusion proteins gain functions not shared by the normal gene counterparts and these fusion protein-specific activities are crucial for the tumorogenic behavior by impacting the control of cell growth/differentiation, apoptosis, and motility. While the two fusion proteins share strong similarity in structural organization, there are significant clinical differences between tumors associated with their expression, indicating a distinction between the biological activities of the two proteins. Our approach to address these research aims involve a combination of biochemical and genetic analysis in tumor-derived cell lines, engineered mammalian cell culture systems, and animal models. We expect that these molecular data will provide insights into defects that are uniquely associated with RMS development as well as defects that are shared by other tumor classes. Ultimately, such understanding will enable us to improve the process of patient diagnosis/or prognosis and to refine the design of therapeutic reagents that specifically interrupt tumor function without damaging normal cell function.
Wang, C. (2012) Childhood rhabdomyosarcoma: recent advances and future prospective. J. Dental Research 91: 341-350 (originally published on line September 13, 2011 DOI: 10.1177/0022034511421490)
Li, H., and Wang, C. (2011) Post-transcriptional regulation of PDGF alpha-receptor in O-2A glial progenitor cells. J. Clinical and Experimental Medicine 4:241-251.
Zhang, Y., and Wang, C. (2011) Nephroblastoma overexpressed (NOV) gene: a paired-domain specific PAX3-FKHR transcription target that promotes survival and motility in alveolar rhabdomyosarcoma cells. Oncogene 30:3549-3562 (originally published on line March 21, 2011 DIO: 10.1038/onc.2011.69)
Zhang, Y., Schwartz, J., and Wang, C. (2009) Comparative analysis of paired- and homeodomain-dependent roles in PAX3-FKHR oncogenesis. Journal of Clinical and Experimental Pathology 2:371-383.
Nishijo, K., Chen, Q.R., Zhang, L., Rodriguez, A., Cho, J., Parajapati, S., Gelfond, J.A.L., Chisholm, G.B., Michalek, J.E., Aronow, B, J., Barr, F., Randall, R. L., Kunkel, L.M., Kang, P.B., Ladanyi, M., Qualman, S.J., Stallings, R.L., Rubin, B.P., LeGallow, R.D., Wang, C., Khan, J.I., and Keller, C. (2009) Credentialing a preclinical mouse model of alveolar rhabdomyosarcoma. Cancer Research 69: 2902-2911.
Zhang L, Wang C. 2007. Identification of a new class of PAX3-FKHR target promoters: a role of the Pax3 paired box DNA binding domain. Oncogene 26(11):1595-605.
Zhang L, Wang C. 2006. F box protein Skp2: A novel transcriptional target of E2F. Oncogene 25: 2615-2617.
Zhang L, Wang C. 2003. PAX3-FKHR transformation increases 26 S proteasome-dependent degradation of p27Kip1, a potential role for elevated Skp2 expression. J Biol Chem 278(1):27-36.
Gnessi L, Basciani S, Mariani S, Arizzi M, Spera G, Wang C., Bondjers C, Karlsson L, Betsholtz C. 2000. Loss of leydig cells and spermatogenic arrest in PDGF A deficient mice. J Cell Biology 149:1019-1026.
Cao Y, Wang C. 2000. The COOH-terminal transactivation domain plays a key role in regulating the in vitro and in vivo function of Pax3 homeodomain. J Biol Chem 275(13):9854-62.
Find out more
- UIC Research Resource Center (RRC)
- UIC Biologic Resource Laboratory (BRL)
- UIC Center for Clinical and Translational Sciences (CCTS)
- Tissue Bank/ Transdisciplinary Pathology
- Chicago Biomedical Consortium
- Library Research Resources and Clinical Tools for Dentistry
- National Institute of Craniofacial and Dental Research