Ph.D., Boston University School of Medicine, 2003
|I study a type of brain cancer known as malignant glioma, which differs from healthy tissue by a small number of defining characteristics. By forcing glioma cells to adopt these healthy traits, we can stop tumor growth. My group searches for therapeutic ways to force this transition.|
Hongwu Zheng’s lab 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, malignant glioma cells conspicuously lack the terminal differentiation traits possessed by their normal counterparts—neural progenitors. With the use of multiple approaches combining human cancer genomics, animal modeling, and stem cell biology, Zheng has unraveled the causal relationship between aberrant differentiation and ensuing gliomagenesis. Perhaps more importantly, his team has demonstrated that forced restoration of differentiation capacity within glioma cells can drastically attenuate their tumorigenic potential. This finding fits well with the team’s overall strategy, which is to target differentiation control pathways as a novel avenue for malignant glioma treatment. To this end, they have sought (1) to develop various animal models to recapitulate the human glioma pathogenesis and utilize them to trace and investigate in vivo tumor initiation/ progression and (2) to identify key pathways/players controlling normal and neoplastic neural progenitor cell renewal and fate determination.
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.
Sontag Foundation Distinguished Scientist Award