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Puran Singh Sijwali

Senior Principal Scientist

Research Interests

Malaria parasite has a wonderfully complex development that involves 15 different forms, disguising the host defence arsenal, to complete its life cycle. Many of these forms reside in different cellular environments and contain stage-specific proteins and functionally specialized organelles, which are produced and disposed off as and when required. Additionally, the parasite not only breaks down host cellular contents to obtain nutrients, it also enslaves many host proteins for its benefit. My lab is investigating the ubiquitin proteasome and lysosomal pathways of malaria parasites, which likely regulate parasite development and disease pathogenesis through degradative and non-degradative functions. We combine gene knock-out/knock-in/knock-down approaches with biochemical and cell biology methods in our studies on both P. falciparum and in vivo models of malaria. We also have a high throughput screening assay for anti-malarial drug discovery.

Selected Publications

Divya N. Nair, Rajesh Prasad, Neha Singhal, Manish Bhattacharjee, Renu Sudhakar, Pushpa Singh, Subramonian Thanumalayan, Uday Kiran, Yogendra Sharma and Puran Singh Sijwali. (2018) A conserved human DJ1-subfamily motif (DJSM) is critical for anti-oxidative and deglycase activities of Plasmodium falciparum DJ1. Molecular & Biochemical Parasitology. 222:70-80. doi:10.1016/j.molbiopara.2018.05.003

Kolla VK, Prasad R, Sayyad Z, Atul, Shah AY, Allanki AD, Navale R, Singhal N, Tanneru N, Sudhakar R, Venkatesan V, Deshmukh MV and Sijwali PS. (2015) Independent amino acid residues in the S2 pocket of falcipain-3 determine its specificity for P2 residues in substrates. Mol Biochem Parasitol. 202(2):11-22. doi: 0.1016/j.molbiopara.2015.09.005.


Navale R, Atul, Allanki AD and Sijwali PS. (2014) Characterization of the autophagy marker protein Atg8 reveals atypical features of autophagy in Plasmodium falciparum. PLoS One 9(11): e113220. doi:10.1371/journal.pone.0113220.

Singhal N, Atul, Mastan B, Arun Kumar K and Sijwali PS. (2014) Genetic ablation of plasmoDJ1, a multi-activity enzyme, attenuates parasite virulence and reduces oocyst production. Biochem. J. 461 (189-203).

Prasad R, Atul, Kolla VK, Legac, J, Singhal N, Navale, R, Rosenthal PJ and Sijwali PS. (2013) Blocking Plasmodium falciparum development via dual inhibition of hemoglobin degradation and the ubiquitin proteasome system by MG132. PLoS One. 8(9):e73530. doi: 10.1371/journal.pone.0073530.


Education & Experiance

P.G: Molecular Biology and Biotechnology ; Govind Ballabh Pant University of Agriculture & Technology, Pantnagar, India ; 1994
Ph.D: Cloning and characterization of the thrombospondin-related adhesive protein (TRAP) from the simian and the human malaria parasites ; International Centre for Genetic Engineering and Biotechnology-Jawaharlal Nehru University, New Delhi, India ; 1999
Post.Doc:

Plasmodium proteases and hemoglobin degradation in erythrocytes ; UNIVERSITY OF CALIFORNIA SAN FRANCISCO, CA, USA ; 1999-2004

Experience:

Assistant Researcher at UNIVERSITY OF CALIFORNIA SAN FRANCISCO, CA, USA from 2004-2008

Publications

TitleJournalYear
A conserved human DJ1-subfamily motif (DJSM) is critical for anti-oxidative and deglycase activities of Plasmodium falciparum DJ1. Molecular & Biochemical Parasitology. 222:70-80. doi:10.1016/j.molbiopara.2018.05.003 2018
Biotransformation of Artemisinin to 14-hydroxydeoxyartemisinin: C-14 hydroxylation by Aspergillus flavus. Journal of Agricultural and Food Chemistry. DOI: 10.1021/acs.jafc.8b03573 2018
A Novel and conserved Plasmodium sporozoite membrane protein SPELD is required for maturation of exo-erythrocytic forms. Sci Rep.7: 40407. doi: 10.1038/srep40407. 2017
Synthesis and evaluation of naphthyl bearing 1,2,3-triazole analogs as antiplasmodial agents, cytotoxicity and docking studies. Bioorg Med Chem. 2017;25(1):221-232. doi: 10.1016/j.bmc.2016.10.029. 2016
Independent amino acid residues in the S2 pocket of falcipain-3 determine its specificity for P2 residues in substrates. Mol Biochem Parasitol. 202(2):11-22. doi: 0.1016/j.molbiopara.2015.09.005. 2015
Emergence of pyrido quinoxalines as new family of antimalarial agents. Eur J Med Chem. 77C:280-287. 2014
Genetic ablation of plasmoDJ1, a multi-activity enzyme, attenuates parasite virulence and reduces oocyst production. Biochem. J. 461 (189-203). 2014
Characterization of the autophagy marker protein Atg8 reveals atypical features of autophagy in Plasmodium falciparum. PLoS One 9(11): e113220. doi:10.1371/journal.pone.0113220. 2014
Synthesis and insight into the structure-activity relationships of chalcones as antimalarial agents. J Med Chem. 2013 Jan 10;56(1):31-45. 2013
Blocking Plasmodium falciparum development via dual inhibition of hemoglobin degradation and the ubiquitin proteasome system by MG132. PLoS One. 8(9):e73530. 2013
The Ionic and Hydrophobic Interactions Are Required for the Auto Activation of Cysteine Proteases of Plasmodium falciparum. PLoS One. 7(10):e47227. 2012
Expression, Characterization, and Cellular Localization of Knowpains, Papain-Like Cysteine Proteases of the Plasmodium knowlesi Malaria Parasite. PLoS One. 2012;7(12):e51619. 2012
Functional evaluation of Plasmodium export signals in Plasmodium berghei suggests multiple modes of protein export. PLoS One 19;5(4): e10227. 2010
Antimalarial effects of human immunodeficiency virus type 1 protease inhibitors differ from those of the aspartic protease inhibitor pepstatin. Antimicrob Agents Chemother 50(6): 2207-2209. 2007
Falcipain cysteine proteases require bipartite motifs for trafficking to the Plasmodium falciparum food vacuole. Journal of Biological Chemistry 282(34):24961-9. 2007
A chimeric cysteine protease of Plasmodium berghei engineered to resemble the Plasmodium falciparum protease falcipain-2. Protein Engineering, Design and Selection 20(4):171-177. 2007
Gene disruptions demonstrate independent roles for the four falcipain cysteine proteases of Plasmodium falciparum. Mol Biochem Parasitol 150(1): 96:106. 2006
Structural basis for unique mechanisms of folding and hemoglobin binding by a malarial protease. Proceedings of the National Academy of Sciences USA 103(31):11503-8. 2006
Plasmodium falciparum: Biochemical characterization of the cysteine protease falcipain-2'. Exp Parasitol 112(3):187-192. 2005
The Plasmodium falciparum cysteine protease falcipain-2 captures its substrate, hemoglobin, via a unique motif. Proceedings of the National Academy of Sciences USA102(26): 9138-9143. 2005
Plasmodium falciparum cysteine protease falcipain-1 is not essential in erythrocytic stage malaria parasites. Proceedings of the National Academy of Sciences USA 101(23): 8721-8726. *Equal Contribution. 2004
Identification and biochemical characterization of vivapains, cysteine proteases of the malaria parasite Plasmodium vivax. Biochemical Journal 378(2): 529-538. 2004
Gene disruption confirms a critical role for the cysteine protease falcipain-2 in hemoglobin hydrolysis by Plasmodium falciparum. Proceedings of the National Academy of Sciences USA 101(13): 4384-4389. 2004
Independent intramolecular mediators of folding, activity, and inhibition for the Plasmodium falciparum cysteine protease falcipain-2. Journal of Biological Chemistry 279(5): 3484-3491. 2004
Critical role of amino acid 23 in mediating activity and specificity of vinckepain-2, a papain-family cysteine protease of rodent malaria parasites. Biochemical Journal 368(1): 273-281. 2002
Folding of the Plasmodium falciparum cysteine protease falcipain-2 is mediated by a chaperone-like peptide and not the prodomain. Journal of Biological Chemistry 277(17): 14910-14915. 2002
Expression and characterization of the Plasmodium falciparum haemoglobinase falcipain-3. Biochemical Journal 360(2): 481-489. 2001
Recombinant falcipain-2 cleaves erythrocyte membrane ankyrin and protein 4.1. Molecular Biochemical Parasitology 116(1): 95-99. 2001
Systematic optimization of expression and refolding of the Plasmodium falciparum cysteine protease falcipain-2. Protein Expression and Purification 22(1): 128-134. 2001
Systematic optimization of expression and refolding of the Plasmodium falciparum cysteine protease falcipain-2. Protein Expression and Purification 22(1): 128-134. 2001
Characterization of native and recombinant falcipain-2, a principal trophozoite cysteine protease and essential hemoglobinase of Plasmodium falciparum. Journal of Biological Chemistry 275(37): 29000-29010. *Equal Contribution. 2000
Cloning and sequence analysis of the thrombospondin-related adhesive protein (TRAP) gene of Plasmodium cynomolgi bastianelli. Molecular Biochemical Parasitology 90(1): 371-376. 1997
Detection and quantitation of Helicoverpa armigera nuclear polyhedrosis virus by ELISA technique. Indian Journal of Microbiology 36: 229-230. 1996
Synthesis and evaluation of anti-plasmodial and cytotoxic activities of epoxyazadiradione derivatives. Eur J Med Chem. 134:242-257. doi: 10.1016/j.ejmech.2017.04.016. 0

Puran Singh Sijwali

Senior Principal Scientist

2926

psijwali@ccmb.res.in

S Thanumalayan

Sr. Technical Officer

2928

thanu@ccmb.res.in

T Nandita

Senior Research Fellow

2928

nandita@ccmb.res.in

Renu Sudhakar

Senior Research Fellow

2928

renusmenon@ccmb.res.in

Manish Bhattacharjee

Junior Research Fellow

2928

manish.atp29@ccmb.res.in

Deepak Kumar

Junior Research Fellow

2928

deepak.kumar@ccmb.res.in

Zeba Rizvi

Junior Research Fellow

2928

zeba@ccmb.res.in

Gangumala Srinivas Reddy

Senior Research Fellow

2928

Puspita Saha

Junior Research Fellow

2928

Subhashree S Sahu

Junior Research Fellow

Divya Das

Junior Research Fellow(Project)

Navin Adhikari

Junior Research Fellow (Project)