In general, our research focuses on understanding the molecular basis of brain tumor development and growth and on using the acquired knowledge to identify new targets and develop new approaches for experimental brain tumor therapy. Specifically, three projects are ongoing in our lab at this time:
Project 1: To study the interactions between the c-Met receptor tyrosine kinase pathway and selected oncogenic and tumor suppressive molecules and pathways: We have previously established the c-Met pathway as a contributor to brain tumor malignancy and growth. Clinically applicable inhibitors of c-Met have been subsequently developed but have thus far failed to achieve significant effects in human patients. We hypothesize that this failure is due to signaling redundancy and compensatory mechanisms involving various other pathways and molecules. Our aim is to understand how c-Met interacts with these pathways and molecules at the molecular and functional levels. The ultimate goal is to use this understanding to develop new multi-therapies that target c-Met in combination with other molecules in order to achieve greater anti-tumor effects.
Project 2: To study the, by us recently discovered, interactions between the tumor suppressor PTEN and mutant p53: We recently discovered that the tumor suppressor PTEN can exhibit unexpected tumor-promoting properties. We have evidence that these tumor-promoting properties of PTEN are due to its interactions with gain-of-function mutant p53. We are systematically studying these, previously unknown, interactions between PTEN and mutant-p53 and their implications for prognosis and the design of anti-tumor therapies. The findings will provide new mechanistic insights into the interactions between PTEN and p53 mutants in human cancer, have prognostic value and determine the settings and pre-conditions under which manipulating tumor suppressor expression and function can lead to successful anti-tumor therapies.
Project 3: To study the role of microRNAs in brain tumor malignancy and assess their potential use as therapeutic targets and therapeutic agents: MicroRNAs are recently discovered small non-coding regulatory RNAs that play important roles in regulating gene expression. We are studying the expressions, mRNA targets and functions of several microRNAs that are predicted to target or mediate the effects of important oncogenic and tumor suppressive molecules in brain tumors. The goal is to understand the role of microRNAs in brain tumor development and growth and identify microRNAs that target or mediate the effects of multiple oncogenic pathways and that can be used as new therapeutic agents or therapeutic targets in brain tumors.