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Ranjit S. Bindra, MD, PhD

Harvey and Kate Cushing Professor of Therapeutic Radiology and Professor of Pathology; Vice Chair for Translational Research, Therapeutic Radiology; Scientific Director, Chênevert Family Brain Tumor Center at Smilow Cancer Hospital and Yale Cancer Center

Contact Information

Ranjit S. Bindra, MD, PhD

Office Location

Mailing Address

  • Therapeutic Radiology

    P. O. Box 208040

    New Haven, CT 06520-8040

    United States

Bindra Lab
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Research Summary

Dr. Ranjit Bindra is a physician-scientist at the Yale School of Medicine and Co-Director of the Yale Brain Tumor Center. In the laboratory, his group recently led a team of four major laboratories at Yale, which reported the stunning discovery that IDH1/2-mutant tumors harbor a profound DNA repair defect that renders them exquisitely sensitive to PARP inhibitors. This work was published in Science Translational Medicine, and Nature, and it has received international attention with major clinical implications Dr. Bindra is now translating this work directly into patients, in four phase I/II clinical trials, including an innovative, biomarker-driven trial specifically targeting the Adolescent/Young Adult (AYA) cancer patient population. Dr. Bindra received his undergraduate degree in Molecular Biophysics and Biochemistry from Yale University in 1998, and both his MD and PhD from the Yale School of Medicine in 2007. He completed his medical internship, radiation oncology residency, and post-doctoral research studies at the Memorial Sloan-Kettering Cancer Center (MSKCC) in 2012.

Extensive Research Description

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.

Coauthors

Research Interests

DNA Repair; Glioma; Medical Oncology; Pediatrics; Radiology; Therapeutics; Central Nervous System Neoplasms; Radiation Oncology; Genomics; High-Throughput Screening Assays

Selected Publications

Clinical Trials

ConditionsStudy Title
LungMRI Brain Surveillance Alone Versus MRI Surveillance and Prophylactic Cranial Irradiation (PCI): A Randomized Phase III Trial in Small-Cell Lung Cancer (MAVERICK)
Brain and Nervous System; PediatricsA Target Validation/Phase1 Study of BGB-290 in Combination With Temozolomide in Adolescent and Young Adult IDH1/2 Newly Diagnosed and Recurrent Mutant Gliomas
Brain and Nervous SystemPhase III Trial of Observation Versus Irradiation for a Gross Totally Resected Grade II Meningioma
Larynx; Lip, Oral Cavity and PharynxRadiation Therapy With Cisplatin, Docetaxel, or Cetuximab After Surgery in Treating Patients With Stage III-IV Squamous Cell Head and Neck Cancer
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