Primary AppointmentMicrobiology, Immunology, and Cancer Biology
Basic and translational brain tumor research
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, the following projects are ongoing in my lab at this time: Project 1: To study the role of non-coding RNAs in brain tumor malignancy and uncover new therapeutic targets Non-coding RNAs are regulatory RNAs that play important roles in regulating normal and cancer biology. We are studying the expressions, targets, mechanisms of action and functions of microRNAs, TUCRs and lncRNAs in gliomas. The goal is to understand their role in brain tumor development and growth and identify new therapeutic targets in brain tumors. Project 2: To study the roles and therapeutic targeting of MET and other RTKs in brain tumors. We have previously established the MET pathway as a contributor to brain tumor malignancy and growth. Clinically applicable inhibitors of MET have been subsequently developed but have thus far failed to achieve significant effects in human patients. We hypothesized that this failure is due to signaling redundancy and compensatory mechanisms involving various other pathways and molecules including other RTKs. Our goals are to understand how MET interacts with these pathways and molecules at the molecular and functional levels, and to use this understanding to develop new therapies that target MET in combination with other molecules in order to achieve greater anti-tumor effects. We are also interested in uncovering the determinants of sensitivity and resistance to MET inhibitors in order to better select patients that will benefit for MET inhibition and to develop new approaches for overcoming resistance to anti-MET drugs. We are also exploring conceptually novel approaches that are based on our new discoveries on ligand-induced oncogene addiction and microRNAs to enhance the efficacy of anti-RTK therapies. Project 3: To investigate Transcribed Ultra-Conserved Regions (TUCR) and long non-coding RNAs (lncRNA) in gliomas TUCR are regions of the genome that are greater than 200 base pairs in length and are highly conserved across two or more species, showing 100% conservation in human, mouse, and rat genomes. A subset of TUCRs are lncRNAs. The expression of TUCRs is commonly deregulated in cancer, where they might exert crucial regulatory roles as lncRNAs. However, the literature elucidating their functional roles and their mechanisms of action in cancer is very sparse, with the literature on their role in glioblastoma being inexistent. This project aims to identify TUCRs that are differentially expressed in glioblastoma, uncover potential correlations with clinical parameters, determine their functional role and mechanisms of action, and evaluate their potential as therapeutic targets. Project 4: To assess the roles and therapeutic targeting of T-Type calcium channels in glioblastoma We are performing a comprehensive investigation of the roles and potential therapeutic exploitation of T-type calcium channels in glioblastoma. Project 5: To investigate the role and therapeutic targeting of TERT promoter mutant glioblastoma We are investigating role and effects of targeting the transcription factor GABP as a new indirect approach to targeting TERT mutant glioblastoma.