Page 41 - Hormel Report 2023

Mechanism of Temozolomide Mediated Radiation Sensitization in Glioblastoma.
This project is based on a well-established paradigm that temozolomide can sensitize glioblastoma cells to radiation, but the mechanisms behind this effect remain the subject for further investigation. This is a project aimed at elucidating the mechanism of radio-sensitization by temozolomide.
Epigenetic Regulation of Glioblastoma Tumor Microenvironment.
Our RNA sequencing data generated using glioblastoma cells expressing shRNA targeting RBBP4 or p300 suggests that these members of RBBP4/p300 complex control genes important for maintaining angiogenic (e.g., HIF1A and VEGFA) and immunosuppressive (e.g., PDL1) glioblastoma microenvironment. We hypothesized that targeting RBBP4/p300 complex may sensitize glioblastoma to angiogenesis and immune check point inhibitors. This project will mechanistically link RBBP4/ p300 with regulation of angiogenesis and immunosuppressive genes and demon- strate the impact of silencing this complex on angiogenesis and immunoreactivity in vitro, and the sensitivity to angiogenesis and immune checkpoint inhibitors
in vivo.
ORCID iD: https://orcid.org/0000-0002-0548-1312
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PUBLICATION HIGHTLIGHT:
• Mladek, A. C., Yan, H. H., Tian, S. L., Decker, P. A., Burgenske, D. M., Bakken, K., Hu, Z., He, L. H., Connors, M. A., Carlson, B. L., Wilson, J., Bommi-Reddy, A., Conery, A., Eckel-Passow, J. E., Sarkaria, J. N., & Kitange, G. J. (2022). RBBP4-p300 axis modulates expression of
genes essential for cell survival and is a potential target for therapy in glioblastoma. Neuro-Oncology, 24(8), 1261-1272.
“My research is important because better understanding of the mechanisms of resistance to therapy will provide targets for developing novel
GBM therapies.”
Gasper Kitange