Medulloblastoma (MB) is the most common malignant pediatric brain tumor. Based on extensive genomic analysis, MB has been classified into four major subtypes. Among these, tumors associated with overexpression or amplification of the oncogenic gene MYC have the poorest prognosis. Even with an intensive regimen of surgery, radiation and chemotherapy, 30 to 40 percent of patients exhibit tumor recurrence and die from their disease. One important cause of relapse is the small number of tumor cells that are initially resistant to radiation and chemotherapy. These cells may become activated and expand into a therapy-resistant and ultimately lethal tumor. Our laboratory, led by Yanxin Pei, PhD, is interested in understanding the mechanisms of therapy resistance and finding ways to target the resistant tumor cells, using both mouse MYC-driven MB model and human MYC-driven MB xenografts.
Our laboratory is also interested in investigating how oncogenes initiate and sustain tumorigenesis in MYC-driven MB. We have developed model systems whereby we can conditionally alter the expression of oncogenes in tumor cells. We are using these model systems to study whether:
- Inactivation of one oncogene can be sufficient to cause complete tumor regression.
- Some tumor cells escape dependence on oncogene and acquire additional genetic mutations during oncogene inactivation.
- These mutations can be new therapeutic targets to combine with oncogene inactivation to prevent tumor recurrence in MB.
Yanxin Pei, Colin E. Moore, Jun Wang, Alok K. Tewari, Alexey Eroshkin, Yoon-Jae Cho, Hendrik Witt, Andrey Korshunov, Tracy-Ann Read, Julia L. Sun, Earlene M. Schmitt, C. Ryan Miller, Anne F. Buckley, Roger E. McLendon, Thomas F. Westbrook, Paul A. Northcot, Michael D. Taylor, Stefan M. Pfister, Phillip G. Febbo and Robert J. Wechsler-Reya. An animal model of MYC-driven medulloblastoma. Cancer Cell. 2012, 21: 155-167.
Yanxin Pei, Sonja N. Brun, Shirley L. Markant, Paul Gibson, Makoto M. Taketo, Marco Giovannini, Richard Gilbertson and Robert J. Wechsler-Reya. WNT signaling increases proliferation and impairs differentiation of stem cells in the developing cerebellum. Development. 2012, 139:1694-1703.
Yanxin Pei, Wechsler-Reya. A malignant oligarchy: progenitors govern the behavior of oligodendrogliomas. Cancer Cell. 2010, 18(6): 669-82. [PMC3012268]
Paul Gibson, Yiai Tong, Giles Robinson, Margaret C. Thompson, D. Spencer Currle, Christopher Eden, Twala Hogg, Helen Poppleton, Julie Martin, David Finkelstein, Stanley Pounds, Zoltan Patay, Matthew Scoggins, Robert Ogg, Yanxin Pei, Sonja Brun, Youngsoo Lee, Frederique Zindy, Janet C. Lindsey, David H. Gutmann, Frederick A. Boop, Robert A. Sanford, Amar Gajjar, Steven C. Clifford, Martine F. Roussel, Peter J. McKinnon,Makoto M. Taketo, David W. Ellison, Robert Wechsler-Reya, Richard J. Gilbertson. Subtypes of medulloblastoma have distinct developmental origins. Nature. 2010, 468, 1095-1099. [PMC3059767]
Yanxin Pei, Xiangping He and Zuoping Xie. Survival and differentiation of dopaminergic neurons can be regulated by developmental signals from cortex in Vitro. Neuroreport. 2004, 15(12), 1847-1850.
Yanxin Pei, Lin Geng, Xiangping He and Zuoping Xie. Heparin regulates survival and differentiation of mesencephalic progenitors mediated by FGF2. Neuroreport. 2004, 15(10), 1643-1647.! 2!
Yanxin Pei, Xiangping He and Zuoping Xie. Dopaminergic neuron differentiation of ventral mesencephalic progenitors regulated by developmental signals in vitro. Neuroreport. 2003, 14(12), 1567-1570.