Contact1307 Chevron Science Center
219 Parkman Avenue
Pittsburgh, PA 15260
Chemical Approaches towards Diagramming Epigenetic Network in Human Development and Disease
Organic Synthesis, Bioorganic Chemistry, Small Molecule Therapeutics, Biochemistry, Protein Engineering and ‘Chromatinomics’ (Chromatin-based Proteomics and Genomics)
We are actively engaged in investigating molecular details of biological processes, particularly those where small organic functionalities when coupled to macromolecules dictate the course of living systems. Chemical modifications on genetic material (DNA) and its packaging elements (Histones) coupled with ATP-dependent chromatin remodeling constitute an epigenetic mechanism that is known to regulate gene transcription, cellular differentiation and organismal development. However, molecular understanding of how these chemical events (establishment and reversal of methylation, acetylation; and ATP hydrolysis) occurring in chromatin landscape control nuclear processes is just beginning to emerge. The focus of our research is to apply chemical principles and methods in understanding these processes that are hard to define by conventional biological methods alone. Given the highly dynamic nature of chromatin-templated events to allow fast cellular responses to developmental/external cues, the scope for applying small-molecule tools to deconvolute the complexity of these signaling pathways is enormous. We are focusing on three areas of epigenetic mechanisms that are at best partially understood: (i) reversal of DNA methylation, (ii) recognition of chromatin modification by ‘reader’ modules, and (iii) ATP-dependent chromatin remodeling.
Deregulation in above-mentioned processes can cause chromosomal instability, and eventually lead to multiple disorders including cancer and neurological diseases. Molecular rationale linking these epigenetic events to disease states is lacking. For example, how mutations in various gene products in these pathways play role in tumorigenesis, tumor progression and metastasis is not completely clear. We envision an active research program to potentiate therapeutic endeavors through the following interconnected goals: (i) to develop novel chemical tools to probe epigenetic processes both in normal and disease states, (ii) to identify new epigenetic drug targets, and (iii) to develop small molecule modulators for these targets.
Our research takes a multidisciplinary approach that integrates organic synthesis, protein engineering, mechanistic biochemistry, proteomics and transcriptomics in order to interrogate cellular machineries towards molecular understanding of epigenetic mechanisms in human health and disease.
- Visiting Research Fellowship by Starr Cancer Consortium (2010)
- Graduate Research Fellowship by Council for Scientific and Industrial Research, New Delhi, India (1999-04)
- Institute Proficiency Prize, Department of Chemistry, Indian Institute of Technology, Kharagpur, India (1999)
- Institute Silver Medal, Indian Institute of Technology, Kharagpur, India (1999)
- Summer Research Fellowship, Tata Institute of Fundamental Research, Mumbai, India (1998)