"My career goal is to elucidate the complex biology of malignant glioma pathogenesis with the aim of translating that new knowledge into patient benefits. At this critical stage of my career, it is my firm belief that the Sontag Foundation Distinguished Scientist Award will be instrumental in helping me achieve my goals."
- Dr. Hongwu Zheng
- Assistant Professor, Cold Spring Harbor Laboratory (08-2010-present)
About DSA-Funded Research
Malignant glioma represents the most common and lethal type of brain tumors resistant to all currently available clinical therapies. In the last several decades, much progress has been made in identifying genetic and genomic alterations that underlie malignant glioma pathogenesis. However, these findings have so far not translated into significant clinical benefit, underscoring the urgent need to explore new paths and novel drug targets through an enhanced understanding of this tragic disease. Biologically, malignant glioma is well known for explicit intratumoral heterogeneity and its lack of terminal differentiation traits. The recent identification of tumor-initiating cells with stem cell-like properties in malignant gliomas, revealed a level of previously under-appreciated tumor cell plasticity and further suggests targeting glioma cell lineage differentiation as a promising avenue for developing effective therapeutics. Given epigenetic regulation as the core developmental mechanism controlling cellular fate determination, we hypothesize that certain yet identified epigenetic networks are essential for maintaining the aberrant undifferentiated state of glioma tumor-initiating cells. Along this line, we are applying a quantitative glioma cell differentiation reporter system, in conjunction with our customized epigenetic RNAi library, to execute a comprehensive study of the epigenetic modifiers whose suppression will promote glioma cell differentiation and thus reduce tumorigenic potential. The fact that epigenetic aberrations, unlike genetic alterations, are potentially reversible makes the initiative promising and therapeutically relevant. It is our belief that the proposed studies will elaborate a list of novel therapeutic targets that can be enrolled into productive drug discovery and development efforts against malignant gliomas.
"Dr. Zheng possesses all of the qualities predicting success in science - an extraordinary scientist who has the passion and courage to pursue fundamental questions, a sincere and generous colleague and a patient teacher."
Ronald A. DePinho, M.D.
M. D. Anderson Cancer Center
"It is clear to me that Hongwu has strong scientific and leadership potential, and by any metric, is among the top young scientists in this country."
Scott W. Lowe, Ph.D
Memorial Sloan-Kettering Cancer Center
- Klingler S, Guo B, Yao J, Yan H, Zhang L, Vaseva AV, Chen S, Canoll P, Horner JW, Wang YA, Paik JH, Ying H, Zheng H. (2015) Development of resistance to EGFR targeted therapy in malignant glioma can occur through EGFR dependent and independent mechanisms. Cancer Research 75(10):2109-19. NIHMSID: 676026.