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Principal Investigator/Program Director (Last, First, Middle): BIOGRAPHICAL SKETCH Provide the following information for the Senior/key personnel and other significant contributors in the order listed on Form Page 2. Follow this format for each person. DO NOT EXCEED FOUR PAGES. NAME POSITION TITLE Ranjit S. Bindra Assistant Professor eRA COMMONS USER NAME (credential, e.g., agency login) BINDRAR EDUCATION/TRAINING (Begin with baccalaureate or other initial professional education, such as nursing, include postdoctoral training and residency training if applicable.) DEGREE INSTITUTION AND LOCATION MM/YY FIELD OF STUDY (if applicable) Yale University, New Haven, CT Yale University School of Medicine, New Haven, CT Yale University School of Medicine, New Haven, CT B.S. Ph.D. M.D. 05/98 12/05 05/07 Mol Biophys & Biochem Experimental Pathology Medicine A. Personal Statement My research is focused on the development of novel cell-based assays for high-throughput screening using genetic and small molecule approaches, both for the creation of novel therapeutics and for new pathway discovery. In addition, I am interested in the development of synthetic lethal targeting strategies for the treatment of tumors with unique genetic aberrations. My laboratory was formed in July of 2012, and currently it is composed of a lab manager, a postdoctoral research associate, an MD/PhD student, several undergraduates and medical students. I am particularly interested in mentoring students who would like to pursue careers in cancer research, and especially in the field of radiobiology. I recently completed my residency in radiation oncology at Memorial Sloan-Kettering Cancer Center (MSKCC), and I joined the faculty in the Department of Therapeutic Radiology at Yale in the summer of 2012. I was given the opportunity to pursue an 18-month period of protected research during residency at MSKCC, which I completed in July 2012. This research time was supported by the Leonard B. Holman Pathway fellowship program. During this time, I developed and executed a high-throughput assay for DNA repair inhibitors using a novel cell-based assay, which was performed in collaboration with Rockefeller University. This project was supported by an RSNA resident research grant and an MSKCC Brain Tumor Center award. A manuscript describing this project was recently published in Nucleic Acids Research, and a second manuscript is currently in preparation. This work, coupled with my research and publications during my PhD, have equipped me with the necessary skills and experience to begin a career as an independent investigator. Clinically, I am focused on the treatment of adult and pediatric CNS tumors. I am interested in leveraging my translational research and clinical experience as a physician-scientist to conduct future investigator-initiated Phase I trials at Yale, based on the results of the drug and genomics screening efforts in my laboratory. B. Positions and Honors Research and Professional Experience 1999 Pre-IRTA Fellow, National Institutes of Health, Bethesda, MD (Klausner Laboratory) 2000-2007 MD/PhD Program, Yale University, New Haven, CT (Advisor: Peter M. Glazer) 2007-2008 Transitional Year Intern, Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York, NY 2008-2012 PGY-5 Resident, Holman Pathway, Department of Radiation Oncology, Memorial SloanKettering Cancer Center, New York, NY 2012Assistant Professor, Department of Therapeutic Radiology, Yale University School of Medicine, New Haven, CT 2012Assistant Professor, Department of Experimental Pathology, Yale University School of Medicine, New Haven, CT 2012Adjunct Clinical Instructor, Department of Diagnostic Imaging and Therapeutics, University of Connecticut School of Medicine, Farmington, CT PHS 398/2590 (Rev. 06/09) Page Biographical Sketch Format Page Program Director/Principal Investigator (Last, First, Middle): Honors 2004 2004 2005 2005 2006 2007 2007 2008-2012 2010 2010 2010 2010 2011 2011 2012 Marie Curie Award, Radiation Research Society First Place Abstract Award, Tumor Progression and Therapeutic Resistance Conference Junior Investigator Award, 9th Annual Tumor Microenvironment Conference Distinguished PhD Thesis Award, Yale University First place, Helix Therapeutics, Inc., Biotechnology Category, 2006 Y50K Business Plan Competition, Yale Entrepreneurial Society Cum Laude, Yale University Farr Scholar, awarded for the most outstanding MD/PhD thesis B. Leonard Holman Research Pathway, American Board of Radiology Poster Award, Brain Tumor Center Retreat, Memorial Sloan-Kettering Cancer Center Research Resident Grant, Radiological Society of North America Brain Tumor Center Grant winner, Memorial Sloan-Kettering Cancer Center Annual Meeting Scientific Abstract Award, American Society for Radiation Oncology Annual Roentgen Resident/Fellow Research Award, Radiological Society of North America Annual Meeting Scientific Abstract Award, American Society for Radiation Oncology Young Investigator Award, Alex’s Lemonade Stand Foundation C. Selected Peer-reviewed Publications (15 selected from 24 publications) 1. Simon DB, Bindra RS, Mansfield TA, Nelson-Williams C, Mendonca E, Stone R, Schuman S, Navir A, Alpay H, Bakkaloglu A, Rodriguez-Soriano J, Morales JM, Sanjad SA, Taylor CM, Pilz D, Brem A, Trachtman H, Griswold W, Richard GA, John E, & Lifton RP. (1997) Mutations in the chloride channel gene, CLCNKB, cause Bartter’s Syndrome Type III. Nature Genetics 17: 171-178. 2. Bindra RS, Vasselli JR, Stearman RS, Linehan WM, & Klausner RD. (2002) VHL-mediated hypoxia regulation of cyclin D1 in renal carcinoma cells. Cancer Res. 62: 3014-9. PMID: 12036906 3. Mihaylova VT, *Bindra RS, Yuan J, Campisi D, Narayanan L, Jensen R, Giodano F, Johnson RS, Rockwell S, & Glazer PM. (2003) Decreased Expression of the DNA Mismatch Repair Gene Mlh1 under Hypoxic Stress in Mammalian Cells. Mol Cell Biol. 23: 3265-73. [*co-first Author]. PMCID: PMC153206 4. Bindra RS, Schaffer PJ, Meng A, Woo J, Maseide K, Roth ME, Lizardi P, Hedley DW, Bristow RG, & Glazer PM. (2004) Down-regulation of Rad51 and decreased homologous recombination in hypoxic cancer cells. Mol Cell Biol. 24: 8504-18. PMCID: PMC516750 5. Meng AX, Jalali F, Cuddihy A, Chan N, Bindra RS, Glazer PM, Bristow RG. Hypoxia down-regulates DNA double strand break repair gene expression in prostate cancer cells. Rad Oncol. 2: 168-76, 2005. 6. Gibson SL, Bindra RS, & Glazer PM. (2005) Hypoxia-induced phosphorylation of Chk2 in an ATMdependent manner. Cancer Res. 23, 65: 10734-41. PMID: 16322218 7. Bindra RS, Gibson SL, Meng A, Westermark U, Jasin M, Pierce AJ, Bristow RG, Classon MK, & Glazer PM. (2005) Hypoxia-induced down-regulation of BRCA1 expression by E2Fs. Cancer Res. 24, 65:1159711604. 8. Gibson SL, *Bindra RS, & Glazer PM. (2006) Chk2-dependent phosphorylation of BRCA1 in hypoxia. Radiat Res.166, 4:646-51. [*Indicates co-first Author]. PMID: 17007555 9. Bindra RS, Glazer, PM. (2006) Basal repression of BRCA1 by multiple E2Fs and pocket proteins via adjacent E2F sites. Cancer Bio. Ther. (10): 1400-7. PMID: 17106239 10. Bindra RS, Glazer PM. (2007) Repression of RAD51 gene expression by E2F4/p130 complexes in hypoxia. Oncogene. 26(14): 2048-5. PMID: 17001309 11. Bindra RS, Glazer PM. (2007) Co-repression of mismatch repair gene expression in hypoxia: role of the Max network. Cancer Lett. 252(1): 93-103. PMID: 17275176 12. Chan N, Koritzinsky M, Zhao H, Bindra RS, Glazer PM, Powell S, Belmaaza A, Wouters B, & Bristow RG. (2008) Chronic hypoxia decreases synthesis of homologous recombination proteins to offset chemoresistance and radioresistance. Cancer Res. 68(2): 605-14,. PMID: 18199558 13. Hegan DC, Lu Y, Stachelek GC, Crosby ME, Bindra RS, & Glazer PM. (2010) Inhibition of poly(ADPribose) polymerase down-regulates BRCA1 and RAD51 in a pathway mediated by E2F4 and p130. Proc Natl Acad Sci U S A. 107(5): 2201-6. PMCID: PMC2836641 PHS 398/2590 (Rev. 06/09) Page Biographical Sketch Format Page Program Director/Principal Investigator (Last, First, Middle): 14. Bindra RS & Yahalom J. (2011) The important role of radiation therapy in early stage diffuse large B-cell lymphoma: Time to review the evidence once again. Expert Rev Anticancer Ther. 11(9):1367-78. PMID: 21929311 15. Bindra RS, Goglia AG, Jasin M, & Powell SN. (2013) Development of an assay to measure mutagenic non-homologous end joining repair activity in mammalian cells. Nucleic Acids Research, Apr 12. PMID: 23585275 D. Research Support Ongoing Research Support Young Investigator Award Bindra (PI) 07/01/12-07/01/14 Alex’s Lemonade Stand Foundation Small Molecule Screening for Novel Pediatric Glioma Radiosensitizers. The major goals of this project are to screen for, validate, and test novel radiosensitizers in a panel of pediatric glioma cell lines and intracranial tumor xenografts. Role: PI Just-in-Time Core Technologies Bindra (PI) 11/01/12-10/31/13 Yale Center for Clinical Investigation Development of Novel Methods to Assess DNA Repair Status in Primary Cell Cultures using Next Generation Sequencing. The major goal of this project is to develop a novel protocol that will allow the measurement of nonhomologous end joining (NHEJ) repair in living cells, which can be applied to both established cancer lines and primary cell cultures. Role: PI 2012 Year-End (Pilot) Grant Bindra (PI) 01/01/13-12/31/13 Joanna McAfee Childhood Cancer Foundation Creation of Cell Lines with Inducible PAX3/7-FOX01 Expression Vectors. The goal of this pilot project is to create cell lines containing inducible PAX3- and PAX7-FOX01 fusion protein expression vectors. U2OS cell lines engineered to express these fusion proteins will be initially validated with a small library of drugs in 96-well microplates plates using conventional, manually operated flow cytometry. The goal of these experiments is to demonstrate that our novel cell lines are suitable for use in future drug screening campaigns. Such future screens would utilize automated confocal microscopy to detect mixed populations of cells expressing fusion proteins or an empty vector. Role: PI Pilot Project Program Bindra (PI) 06/01/12-06/30/13 Yale Center for Molecular Discovery High-content, High Throughput Screening for Novel DNA Repair Inhibitors. The major goal of this project is to develop a novel, cell-based high-throughput screening platform to identify modulators of DNA repair pathways, using both small molecule and small interfering RNA (siRNA) libraries. Role: PI Yale Cancer Center Pilot Research Grant 04/01/13 - 04/01/14 0.00 calendar High-throughput Screening for k-ras Mutant Cell Tumor Radiosensitizers The goal of this project is to perform a pilot small molecule screen for compounds which selectively radiosensitize K-ras mutant NSCLC cells, using an isogenic WT and mutant K-ras human cell line model. Completed Research Support None PHS 398/2590 (Rev. 06/09) Page Biographical Sketch Format Page