Ph.D., Boston University School of Medicine, 2003
Our research aims to define the complex biology of malignant glioma pathogenesis with the ultimate goal of translating the developed knowledge into patient benefits. Although eerily similar in terms of their self-renewal capacity and distinct phenotypic plasticity, conspicuously the maligant glioma cells lack the terminal differentiation traits possessed by their normal counterparts – neural progenitors. Using multiple approaches combining human cancer genomic, animal modeling and stem cell biology, we unraveled the causal relationship between aberrant differentiation and its ensuing gliomagenesis; and more importantly, we found forced restoration of differentiation capacity in the glioma cells can drastically attenuate their tumorigenic potential, further reinforcing our view of targeting differentiation control pathways as the novel avenues for malignant glioma treatment.
Along these lines, we have directed our research around two major areas: (1) develop various animal models to recapitulate the human glioma pathogenesis and utilize them to trace and investigate the in vivo tumor initiation/progression; (2) identify key pathways/players controlling normal and neoplastic neural progenitor cell renewal and differentiation. It is our firm belief that an improved understanding of the pathways governing self-renewal and differentiation processes along the neural progenitor-glial axis and, by extension, the glioma initiation cells-progeny axis, will serve instrumental in guiding future development of efficient treatments targeting this dreadful disease.
Zheng, H., Ying, H., Wiedemeyer, R., Yan, H., Quayle, S.N., Ivanova, E.V., Paik, J.H., Zhang, H., Xiao, Y., Perry, S.R., Hu, J., Vinjamoori, A., Gan, B., Sahin, E., Chheda, M.G., Brennan, C., Wang, Y.A., Hahn, W.C., Chin, L., and DePinho, R.A. 2010. PLAGL2 regulates Wnt signaling to impede differentiation in neural stem cells and gliomas. Cancer Cell 17: 497-509.
Ying, H., Zheng, H., Scott, K., Wiedemeyer, R., Yan, H., Huang, J., Dhakal, S., Lim, C., Ivanova, E.V., Xiao, Y., Stommmel, J.M., Paik, J.H., Chen, A., Lee, M., Segatto, O., Wang, Y.A., Chin, L., and DePinho, R.A. 2010. MIG6 regulates EGFR trafficking and represses malignant glioma pathogenesis. Proc. Natl. Acad. Sci. USA. 107: 6912-6917.
Zheng, H., Ying, H., Yan, H., Kimmelman, A.C., Hiller D.J., Chen, A.J., Perry, S.R., Tonon, G., Chu, G.C., Ding, Z., Stommel, J.M., Dunn, K.L., Wiedemeyer, R., You, M.J., Brennan, C., Wang, Y.A., Ligon, K.L., Wong, W.H., Chin, L., and DePinho, R.A. 2008 p53 and Pten control neural and glioma stem/progenitor cell renewal and differentiation. Nature 455: 1129-1133.
Zheng, H., Ying, H., Yan, H., Kimmelman, A.C., Hiller D.J., Chen, A.J., Perry, S.R., Tonon, G., Chu, G.C., Ding, Z., Stommel, J.M., Dunn, K.L., Wiedemeyer, R., You, M.J., Brennan, C., Wang, Y.A., Ligon, K.L., Wong, W.H., Chin, L., and DePinho, R.A. 2008. Pten and p53 converge on c-Myc to control differentiation, self-renewal, and transformation of normal and neoplastic stem cells in glioblastoma. Cold Spring Harbor Symp. Quant. Biol. 73: 427-37.
Zheng, H., You, H., Zhou, X.Z., Murray, S.A., Uchida, T., Wulf, G., Gu, L., Tang, X., Lu, K.P., and Xiao, Z-X.J. 2002. The prolyl isomerase Pin1 is a regulator of p53 in genotoxic response. Nature 419: 849-853.