Ranjit S. Bindra, MD, PhD

As a physician-scientist at the Yale School of Medicine, I am focused on translating the most cutting-edge basic scientific discoveries into innovative, biomarker-driven clinical trials for glioma and other solid tumors. I also serve as co-director of Yale’s Brain Tumor Center. I run a highly translational DNA repair laboratory at Yale. We perform small molecule, siRNA, and CRISPR/Cas-based screens to identify novel, tumor-specific synthetic lethal interactions that can be exploited for a therapeutic gain. In addition, our group is interested in novel, nanoparticle-based drug delivery strategies to bypass the blood-brain barrier and to allow more efficacious drug combinations. Our group recently made the seminal discovery that oncometabolites induce a BRCAness state which can be exploited by PARP inhibitors. This work was published in Science Translational Medicine and Nature Genetics. Most recently, we have further elucidated the mechanistic basis for mutant IDH1/2-induced BRCAness, and this work was published recently in Nature.

We have also identified two novel synthetic lethal interactions in recent work: (1) DIPG-associated PPM1D mutations confer exquisite NAMPT inhibitor (NAMPTi) sensitivity via NAPRT silencing (which is the focus of the current application); and (2) Loss of MGMT confers synergistic tumor cell killing with ATR inhibitor and TMZ combinations. These two studies were published in Nature Communications and Cancer Research, respectively.

I am actively translating the work from our laboratory and others directly into investigator-initiated (IIT) phase I/II trials. To this end, I recently designed and executed a phase I trial in glioma, which tested a DNA repair inhibitor that our laboratory identified in a high-throughput drug screen. This trial included a phase 0 component, in which we assessed CNS penetration of the drug. I am also the PI or co-PI of three biomarker-driven Phase I/II trials, which are testing the use of PARP inhibitors against IDH1/2-mutant gliomas and other solid tumors. Clinically, I maintain a radiation oncology practice focused on the treatment of adult and pediatric brain tumors.