Research in the Sinha group focuses on understanding host defenses against pathogens, the cross-regulation of these defenses and the evasion of these defenses by pathogens in atomic detail. Our goal is to obtain a detailed yet comprehensive picture of host-pathogen interactions, to facilitate the rational development of therapeutics. Our immediate focus is the mechanism of two such pathways: Autophagy and cytoplasmic receptor-triggered innate immune pathways; as well as the inhibition of these pathways by viruses. 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.
Sinha, S. & Levine, B.(2009). The autophagy effector Beclin 1: A novel BH3-only protein. Oncogene 27, S137-S148.
Sinha, S., Colbert, C.L., Becker, N., Wei, Y. & Levine, B.(2008). Molecular basis of the regulation of Beclin 1-dependent autophagy by the γ-herpesvirus 68 Bcl-2 homolog M11. Autophagy 4, 989-997.
Wei, Y., Sinha, S. & Levine, B.(2008). Dual role of JNK1-mediated phosphorylation of Bcl-2 in autophagy and apoptosis regulation. Autophagy 4, 949-951.
Levine, B., Sinha, S. & Kroemer, G.(2008). Bcl-2 family members: dual regulators of apoptosis and autophagy. Autophagy 4, 600-606.
Wei, Y., Pattingre, S., Sinha, S., Bassik, M. & Levine, B.(2008). JNK-mediated phosphorylation of Bcl-2 regulates starvation-induced autophagy. Mol. Cell. 30, 678-688.
Saito, T., Hirai, R., Loo, Y.-M., Owen, D., Johnson, C.L., Sinha, S.C., Akira, S., Fujita, T. & Gale, M., Jr.(2007). Regulation of innate antiviral defenses through a shared repressor domain in RIG-I and LGP2. Proc. Natl. Acad. Sci., USA. 104, 582-587.
Sinha, S.C. & Sprang, S.R.(2006). Structures, mechanism, regulation and evolution of Class III nucleotidyl cyclases. Rev. Physiol. Biochem. Pharmacol. 157, 105-140.
Sinha, S.C., Wetterer, M., Sprang, S.R., Schultz, J.E. & Linder, J.U.(2005). Origin of asymmetry in adenylyl cyclases: structures of Mycobacterium tuberculosis Rv1900c. EMBO J. 24, 663-673.
Sinha, S.C., Chaudhari, B.N., Burgner, J.W., Yakovleva, G., Davisson, V.J. & Smith, J.L.(2004). Crystal Structure of Imidazole Glycerol Phosphate Dehydratase: Duplication of an unusual fold. J. Biol. Chem. 279, 15491-15498.
Sinha, S.C., Krahn, J.M., Shin, B.S., Tomchick, D.R., Zalkin, H. & Smith, J.L.(2003). The Purine Repressor of Bacillus subtilis: A novel combination of domains adapted for transcription regulation. J. Bacteriol. 185, 4087-4098.
Sinha, S.C. & Smith, J.L.(2001). The PRT protein family. Curr. Opin. Struct. Biol. 11, 733-739.
Sinha, S., Rappu, P., Lange, S.C., Mäntsälä, P., Zalkin, H. & Smith, J.L.(1999). Crystal structure of Bacillus subtilis
YabJ, a purine regulatory protein and member of the highly conserved YjgF family. Proc. Natl. Acad. Sci., USA. 96, 13074-13079.
Krahn, J.M., Sinha, S. & Smith, J.L.(1999). Successes and prospects for SeMet MAD and large structures. Trans. Am. Crystallogr. Assoc. 34, 27-38.