Research Summary

Establishing a Center for Molecular Medicine

My goal is to establish a Center for Molecular Medicine to accelerate biomedical research and translation in a clinical setting. This core of this center will be a multi-disciplinary scientific team that will leverage the outstanding clinical resources and capabilities of NIMHANS and Kidwai Memorial Institute of Oncology to initiate research programs using a systems biology approach. Several sophisticated technology platforms - next generation sequencing, genome editing, mass spectrometry and bioinformatics – will be employed to drive the research that will be centered on the following themes:

1. Cancer and personalized medicine

We will characterize glioblastoma and gastric adenocarcinoma using genomic (exome sequencing) and proteomic approaches. We will generate cellular and animal models of these tumors and use them to identify activated signaling pathways and to test pharmacological inhibitors. We will also develop assays for detecting mutant cell free DNA in blood.

2. Cancer signaling

We will develop a platform for using CRISPR/Cas9-based genome editing to generate isogenic cells expressing potential oncogenic drivers for systematic analysis of such mutations.

3. Protein Biomarkers

i) Parkinson’s disease: Parkinson’s disease is a neurodegenerative disorder for which there are currently no clear diagnostic or prognostic biomarkers for clinical use. We will apply mass spectrometry-based discovery and targeted validation approaches to identify novel biomarker candidates.

ii) Traumatic brain injury: Traumatic brain injury (TBI) is a major cause of morbidity in vehicular accidents, contact sports and in military personnel. The consequences of mild TBI include somatic, cognitive and behavioral symptoms whose biological underpinnings remain poorly understood. We will carry out mass spectrometry-based discovery experiments to identify potential biomarkers for TBI.

Figure Legend: Characterization of glioblastomas using genomic and proteomic approaches. The tumor exomes will be sequenced and the putative driver mutations will be monitored in the blood of patients. CRISPR/Cas9 based gene editing will be used to insert the identified driver mutations into normal cells to generate isogenic cellular models. These cells will be monitored for changes in their phenotypes induced by the driver mutations. The tumor tissue and cells engineered to contain potential driver mutations will be propagated in mice to study activated signaling pathways and test efficacy of drugs.