Santosh Kumar Jha

Santosh Kumar Jha, Ph.D.

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Protein folding, function and disease

Proteins are functional entities in all living systems. They perform numerous functions including catalysis of chemical reactions, transport of ions and molecules, coordination of motion, provision of mechanical support, generation and transmission of nerve impulses, and control of growth and differentiation. Inside living cells,a protein molecule is synthesized as a linear unfolded polypeptide chain which must fold to a unique three dimensional structure in order to be functional. An error in this process leads to fatal diseases. My research is focused on understanding the rules which govern the folding and unfolding of proteins and how the acquisition of correct structure imparts specific functionality to these biomolecules. I employ a highly interdisciplinary approach to address these problems by combining the tools of biochemistry, molecular biology, theory, and advance spectroscopy, including time-resolved fluorescence resonance energy transfer (TR-FRET) technique, time-resolved infrared spectroscopy and thiol-disulfide exchange methodology coupled to mass spectrometry. The long term goal of my research is to understand how the structure and dynamics of biological macromolecules contribute to biological function, how they are altered in disease and how they can be exploited for therapeutic benefit. 

Selected Publications:

Jha SK*, Ji M*, Gaffney KJ, Boxer SG (2011) Direct measurement of the protein response to an electrostatic perturbation that mimics the catalytic cycle in ketosteroid isomerase. Proc. Natl. Acad. Sci. USA., 108:16612-16617. * indicates joint first author.

Jha SK, Dhar D, Krishnamoorthy G, Udgaonkar JB (2009) Continuous dissolution of structure during the unfolding of a small protein. Proc. Natl. Acad. Sci. USA., 106:11113-11118.

Jha SK, Udgaonkar JB (2007) Exploring the cooperativity of the fast folding reaction of a small protein using pulsed thiol labeling and mass spectrometry. J. Biol. Chem., 282:37479-37491.