Sinha Lab





The overarching goal of the Sinha Laboratory is to understand in atomic detail how biological macromolecules are uniquely designed to carry out functions essential for life. The current focus of our research is to investigate the structural and mechanistic basis of Autophagy, a cellular process found in all eukaryotic cells that is essential for cellular homeostasis. Autophagy is the cellular process responsible for removal and recycling of large and stable macromolecular assemblies, such as ultra-stable proteins, protein aggregates, organelles, and intracellular pathogens; by engulfing these targets in multi-layered vesicles followed by fusion with and degradation by the lysosome. Dysfunction of autophagy has been implicated in lysosomal storage diseases like Neimen-Pick and Tay-Sachs diseases; abnormal embryonic and fetal development (due to inefficient remodeling of cells); neurodegenerative diseases like Parkinson’s and Alzheimer’s (due to accumulation of protein aggregates); heart diseases (due to remodeling of cardiac tissue in response to stress condition); cancers and aging (due to inadequate removal of mutant / damaged proteins); and numerous infectious diseases (due to inadequate removal of pathogens). We are investigating the basic molecular mechanism of proteins that implement and regulate autophagy; the cross-talk between autophagy and other important cellular processes like apoptosis and innate immunity; the manipulation of autophagy by intracellular pathogens, especially viruses; as well as the design of therapeutics to disrupt the function of these viral proteins. While the X-ray crystal structure determination of proteins and protein complexes is the center of our research focus, we use a broad range of techniques including mutagenesis, biochemical and spectroscopic assays, and cell-based methods to supplement and confirm the knowledge we obtain from our structural analyses.





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