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Sangita Sinha

Research Focus

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.

Selected Publications

Glover, K., Mei, Y. & Sinha, S. Identifying Intrinsically Disordered Protein Regions Likely to Undergo Binding-Induced Helical Transitions. Biochimica et Biophysica Acta - Proteins and Proteomics Under review (2016).

Mei, Y., Ramanathan, A., Glover, K., Christopher , Stanley, C., Sanishvili, R., Chakravarthy, S., Yang, Z., Colbert, C.L. & Sinha, S. Conformational Flexibility Enables Function of a BECN1 Region Essential for Starvation-Mediated Autophagy. Biochemistry Under review (2015).

Klionsky, D.J., et. al. Guidelines for the use and interpretation of assays for monitoring autophagy (3rd edition). Autophagy 12, 1-222 (2016).

Jensen, J.L., Balbo, A., Neau, D.B., Chakravarthy, S., Zhao, H., Sinha, S.C. & Colbert, C.L. Mechanistic implications of the unique structural features and dimerization of the cytoplasmic domain of the Pseudomonas sigma regulator, PupR. Biochemistry 54, 5867−5877 (2015).

Wei, Y., An, Z., Zou, Z., Sumpter, R., Su, M., Zang, X., Sinha, S., Gaestel, M. & Levine, B. The stress-responsive kinases MAPKAPK2/MAPKAPK3 activate starvation-induced autophagy through Beclin 1 phosphorylation. LID - 10.7554/eLife.05289 [doi]. eLife 4(2015).

Su, M., Mei, Y., Sanishvili, R., Levine, B., Colbert, C.L. & Sinha, S. Targeting γ-herpesvirus 68 Bcl-2–mediated down-regulation of autophagy. Journal of Biological Chemistry 289, 8029-8050 (2014).

Mei, Y., Su, M., Soni, G., Salem, S., Colbert, C. & Sinha, S. Intrinsically disordered regions in autophagy proteins. PROTEINS: Structure, Function and Bioinformatics 82, 565–578 (2014).

He, C., Wei, Y., Sun, K., Li, B., Dong,X., Zhongju, Z., Liu,Y., Kinch, L. N., Khan, S., Sinha, S., Xavier, R.J., Grishin, N. V., Xiao, G., Eskelinen, E-L., Scherer, P. E., Whistler, J. L. and Levine, B. Beclin 2 Functions in Autophagy, Degradation of G Protein-Coupled Receptors, and Metabolism. Cell. 154, 1085-1099 (2013). PMID: 23954414

Su, M., Mei, Y. & Sinha, S.* Role of the Crosstalk between Autophagy and Apoptosis in Cancer. J. Oncol. 2013, 102735 (2013). doi:10.1155/2013/102735
Colbert, C.L., Agar, N.Y.R., Kumar, P., Chakko, M.N., Sinha, S.C., Powlowski, J.B., Eltis, L.D. & Bolin, J.T. Structural Characterization of Pandoraea pnomenusa B-356 Biphenyl Dioxygenase Reveals Features of Potent Polychlorinated Biphenyl-Degrading Enzymes. PloS ONE 8, e52550 (2013).  PMID: 23308114

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.

Other Publications

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.

Yakovleva, G.M., Hawkes, T.R., Sinha, S., Smith, J.L. & Davisson, V.J. Metal ion assembly of imidazole glycerol phosphate dehydratase (HIS3) from cryptoccocvs neoformans and saccharomyces cerevisiae. FASEB J. 11, A1302 (1997).






Associate Professor

BSc, Delhi University, India, 1990
MSc, University of Poona, India, 1992
PhD, Purdue University, Indiana, 2000
Postdoctoral Fellow, Howard Hughes Medical Institute, University of Texas Southwestern Medical Center, 2005

Office: Quentin Burdick Building 364

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fax 701-231-8324


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