Investigating molecular, genetic, and epigenetic mechanisms of treatment resistance in human tumors and to devise strategies to overcome
Dr. Chakravarti’s Research Group is comprised of multiple faculty members and has a primary focus of investigating the molecular, genetic and epigenetic mechanisms of treatment resistance in human tumors and developing strategies to circumvent this resistance in the clinic. A major focus of the group is on signal transduction pathways, specifically the PI3K/AKT pathway, in glioblastoma and prostate cancer. Dr. Chakravarti is an internationally-recognized cancer researcher and has received continuous federal funding since 1999 to support his research activities. He currently serves as Chair of the RTOG Brain Tumor Translational Research Group and Co-Chair of the clinical RTOG Brain Tumor Committee. Further, he is the United States delegate on the EORTC Brain Tumor Steering Committee. Dr. Chakravarti is a standing member of the NIH Cancer Biomarkers Study Section (CBSS) and serves on NIH PO1 and SPORE review panels, respectively. He has served on national panels that have determined future directions and indications of various targeted therapies. For his accomplishments, Dr. Chakravarti has been recognized as a Fellow of the American College of Radiation Oncology.
Dr. Chakravarti’s research team has uncovered novel therapeutic targets in various tumors such as human gliomas that have led to important international clinical studies investigating novel targeted therapy agents. Further, Dr. Chakravarti’s team has identified novel prognostic and predictive biomarkers in various cancers that has led to revised molecular-based classification schemes for certain tumors such as human glioblastomas (GBMs). Dr. Chakravarti’s team is currently conducting high-throughput molecular, genetic, and epigenetic profiling of brain tumors, prostate cancer, bladder cancer, and melanomas. The correlative approach is genome-wide, including techniques such as SNP, miRNA and global methylation analyses, to identify novel molecular prognostic and predictive biomarkers. Additional research topics include glioma stem cells, DNA repair pathways, tumor microenvironment and cell metabolism. Other disease sites also include melanoma, bladder, gastrointestinal and lung cancer.
Dr. Chakravarti is the Max Morehouse Chair of Cancer Research at Ohio State, where he directs the Brain Tumor Program and chairs the Department of Radiation Oncology. A member of the OSUCCC – James Translational Therapeutics Program, he focuses on translational cancer research to identify novel biomarkers that are predictive of treatment efficacy and survival, and to uncover molecular and genetic mechanisms of treatment resistance to advance care of cancer patients. .
Associate Professor - Clinical
The Chakravarti lab studies different mechanisms of radiation and chemotherapy resistance and sensitivity. Dr. Bell's team is particularly interested in the identification of novel predictive and prognostic molecular biomarkers, specifically biomarkers that can be exploited therapeutically. A fundamental understanding of chemoradiation resistance at the molecular and the whole-genome level will aid in elucidating the mechanisms of radiation resistance in multiple disease sites and will undoubtedly enhance the overall clinical outcomes of many cancer patients. Her current field of research is focused on translational cancer research. In particular, her research areas are correlative analysis on clinical trial tissue including genomic, epigenomic, transcriptomic, and proteomic profiling in order to detect novel tumor biomarkers that correlate with treatment efficacy and survival. She and the team are currently performing whole genome profiling on tissue from multiple Radiation Therapy Oncology Group (RTOG) trials. Their current disease-site focus for the biomarker research is grade III and low-grade gliomas as well as prostate cancer.
Additionally, she is focused on characterizing the effects of chromatin remodeling on DNA repair and chemoradiation resistance and sensitivity. This project will determine if common mutations in chromatin remodeling factors are dominant prognostic and/or predictive biomarkers by comprehensively analyzing the effects of these mutations on DNA repair capacities, characterizing the sensitivity of cells harboring these mutations to specific DNA-damaging therapy modalities and evaluating the correlation of these mutations to clinical outcome data.
Dr. Palanichamy's focus is to bridge the gap between basic and clinical research. To this end, he and the team explore transcriptomic, epigenetic, metabolomic, proteomic and genomic profiles in patient tumor biopsy samples to identify predictive and prognostic markers with a view to identify and validate therapeutic targets. They are also working to identify the underlying mechanisms of chemo and radiation resistance in treatment refractory tumors by short-circuiting signal transduction pathways and determining the mutational status, gene and molecular signatures mediating treatment resistance. They have developed cancer stem cell models to investigate cancer stem cell biology via protein-protein interactions at translational and transcriptional levels. They are conducting correlative biology studies in patient cohorts to determine whether a particular gene, protein, or metabolite contributes to progression free survival, overall survival, and toxicity.