Research in the Shinde Laboratory focuses on understanding the structure, folding, and evolution of proteins, and in particular, how the interactions and dynamics of proteases can regulate their biological functions. The laboratory has recently focused such efforts on a small but vital family of proteases coined proprotein convertases,which are responsible for the proteolytic maturation of pro-protein substrates along the secretory pathway. Proprotein convertases constitute a family of serine endoproteases that activate other proteins ranging from growth factors and receptors to extracellular matrix proteins and even other protease systems that control disease. We are still a long way from having a comprehensive understanding of the mechanisms organelle specific protease activation in cells, the many roles of convertases inside of cells,and the relation between human single nucleotide polymorphisms (SNPs) and specific disease phenotypes. The laboratory studies these proteases by combining biochemical, biophysical, and computational approaches. In addition the lab is developing approaches to create selective, high affinity inhibitors that can discern individual proprotein convertases family members. Given their vital roles, proprotein convertases are now considered to be attractive targets for the development of powerful novel therapeutics.
The Shinde Laboratory also collaborates extensively with researchers on various aspects of structure, function, dynamics, and modeling of transporter function in parasites, copper transporting ATPases in mammals, and protein modification in the tumor progression. These projects help to better understand the mechanisms of complex biological systems in the spirit of mutually beneficial scientific collaboration, while exposing students and researchers to techniques and questions that span the biomedical spectrum.Read more
Areas of interest
- Protein Structure and Function. Protein Folding. Proprotein convertase biochemistry. Bioinformatics and Molecular Modeling. Nucleic Acid Aptamers.
- Ph.D., Pune University 1991
Memberships and associations
- American Association for the Advancement of Science
- American Society for Biochemistry and Molecular Biology
- Biophysical Society
- Protein Society
Elferich J, Williamson DM, Krishnamoorthy B, Shinde U. (2013) Propeptides of eukaryotic proteases encode histidines to exploit organelle pH for regulation. FASEB J. 2013 Aug;27(8):2939-45. doi: 10.1096/fj.12-226886. Epub 2013 Apr 12.
Williamson DM, Elferich J, Ramakrishnan P, Thomas G, Shinde U (2013) The mechanism by which a propeptide-encoded pH-sensor regulates spatiotemporal activation of furin. Journal of Biological Chemistry 2013 Jun 28;288(26):19154-65. doi: 10.1074/jbc.M112.442681. Epub 2013 May 7.
Soysa, R, Wilson, ZN, Elferich, J Forquer, I Shinde, U, Riscoe, MK, Yates, PA, Ullman, B. (2013) Substrate Inhibition of Uracil Phosphoribosyltransferase by Uracil Can Account for the Uracil Growth Sensitivity of Leishmania donovani Pyrimidine Auxotrophs. Journal of Biological Chemistry Oct 11;288(41):29954-64. doi: 10.1074/jbc.M113.478826. Epub 2013 Aug 28.
Davare MA, Saborowski A, Eide CA, Tognon C, Smith RL, Elferich J, Agarwal A, Tyner JW, Shinde UP, Lowe SW, Druker BJ. Foretinib is a potent inhibitor of oncogenic ROS1 fusion proteins. Proc Natl Acad Sci U S A. 2013 Nov 26; 110(48):19519-24. doi: 10.1073/pnas.1319583110.
Yuhuang Li, Xiao-Xin Sun, Johannes Elferich, Ujwal Shinde, Larry L. David, and Mu-Shui Dai Monoubiquitination Is Critical for Otub1 to Suppress UbcH5 and Stabilize p53 Journal of Biological Chemistry (2014) 289(8):5097-108. doi: 10.1074/jbc.M113.533109.
Valdés R, Elferich J, Shinde U, Landfear SM. Identification of the intracellular gate for a member of the equilibrative nucleoside transporter (ENT) family. Journal of Biological Chemistry (2014) 289(13):8799-809. doi: 10.1074/jbc.M113.546960.
Conti, B.J. Elferich, J., Yang Z., Shinde, U and Skach, W.R. Cotranslational Folding Inhibits Translocation from Within the Ribosome–Sec61Translocon Complex Nature Structural and Molecular Biology (2014) 21(3):228-35. doi: 10.1038/nsmb.2779.
Elferich, J., Williamson, D., David L., and Shinde, U. Determination of Histidine pKa Values in the Propeptides of Furin and PC1/3 using Histidine Hydrogen-Deuterium Exchange Mass Spectrometry, Analytical Chemistry (2015),87,7909–17 doi 10.1021/acs.analchem.5b01721.
Williamson, D., Elferich, J., and Shinde, U. Mechanism of Fine-tuning pH Sensors in Proprotein Convertases: Identification of a pH-sensing Histidine Pair in the Propeptide of PC1/3, Journal of Biological Chemistry (2015) 290(38):23214-25. doi: 10.1074/jbc.M115.665430.
Gary Thomas, Joe E Aslan, Laurel Thomas, Puskar Shinde, Ujwal Shinde, and Thomas Simmen Caught in the Act: Protein Adaptation and the expanding roles of the PACS proteins in tissue homeostasis and disease Journal of Cell Science (2017) in press.