Researcher: Biplab Dasgupta PhD
Associate Professor of Pediatrics
Division of Oncology
Research Project: Therapeutic Blockade of Metabolic Dependencies in Diffuse Intrinsic Pontine Glioma
Our earlier work involved characterizing the metabolic landscape of DIPG tumors through untargeted metabolomic analyses on DIPG cell lines and integrated gene expression analyses on the same lines. So far our focus with this data has been on elucidating the connection between DIPG driver mutations and the dysfunctional purine metabolism observed in DIPG cell lines.
Funding from the Team Connor foundation has allowed us to investigate why DIPG cell lines are more sensitive to a specific inhibitor of this pathway while normal cell types are more resistant to this compound. This preliminary data has been instrumental in uncovering why mutations specific to this disease cause these tumor cells to be sensitive to our compound of interest.
Furthermore, our promising in vitro data has led us to investigate the therapeutic potential of this compound in preclinical mouse models for this disease. We have developed a xenograft mouse model that reliably and consistently forms diffuse high grade glioma in mice that can be used for efficacy studies on this inhibitor. Additionally, we have performed some in vivo pharmacokinetic studies in mice with the compound demonstrating the inhibitor does reach the target region of the brain and detectable concentrations of the inhibitor over more than 8 hours after oral administration. These pharmacokinetic studies will allow us to optimize a treatment strategy and perform in vivo efficacy studies while we continue to investigate the mechanism of action of this compound. Data we have collected will allow us to prepare an NIH F31 predoctoral fellowship grant application with a refined research strategy based on sound preliminary data.
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