The candidate is currently in a mentored junior faculty position. She holds two advanced degrees (PhD and DVM) and has performed extensive post-doctoral training in molecular cancer research. Her long term goal is to establish an academic research program, as a tenured professor, aimed at discovering therapeutic targets for cancer. This goal will include teaching, training and mentoring of students in brain tumor research. Her immediate goal is to generate sufficient data and publications over the next 1-2 years to generate a competitive RO1 application. The environment at UAB is strong for cancer research and has a long track record of training successful scientists. Dr. Suswam is currently supported by the UAB Brain Tumor SPORE and the Comprehensive Cancer Center. Her association with successful senior scientists within these entities will help her mature quickly as an independent investigator. These groups have provided her with funds and resources to generate preliminary data for the current research proposal. The broad, long- term goal of this research project is to define the role of the molecular pathway of RNA stabilization in glioma growth and ultimately its potential as a target for anti-cancer therapy. Posttranscriptional gene regulation represents a novel and promising pathway for therapeutic targeting because many of the critical genes involved in tumor progression, including interleukin (IL)-8, VEGF, and TNF-ct, are up-regulated at this level. The production of these factors by glioma cells is shown to correlate strongly with the malignant phenotype. The RNA destabilizing factor, tristetraprolin (TTP), has recently been identified as a critical attenuator of growth factor signaling in normal states. In glioma tumors, however, we have observed that TTP is downregulated and hyperphosphorylated to a relatively inactive state. When TTP is overexpressed in MG as a transgene, we observe destabilization of growth factor mRNAs and cell death. We hypothesize that the destabilizing and cytotoxic effect of TTP is held in check due to posttranslational modifications (hyperphosphorylation) of TTP in MG cells. The following aims are proposed: 1) characterize expression and posttranslational modifications of TTP and effect on growth factor expression and glioma cell phenotype, 2) identify the mechanism of TTP-induced cell death and assess impact of the TTP-induced effects on MG tumor growth in a xenograft model.
|Suswam, Esther A; Shacka, John J; Walker, Kiera et al. (2013) Mutant tristetraprolin: a potent inhibitor of malignant glioma cell growth. J Neurooncol 113:195-205|
|Li, Xuelin; Lin, Wei-Jye; Chen, Ching-Yi et al. (2012) KSRP: a checkpoint for inflammatory cytokine production in astrocytes. Glia 60:1773-84|