Chetan CHITNIS

Information

Scientific interests and projects

Our laboratory is interested in understanding the biology of blood stage malaria parasites. In particular we are interested in understanding the molecular processes that mediate merozoite egress from schizonts and merozoite invasion of RBCs. We study receptor-ligand interactions that mediate RBC invasion and the signaling processes that regulate steps such as microeneme and rhoptry secretion that are critical for receptor engagement during invasion. Information on parasite proteins involved in invasion will be used to develop multivalent blood stage vaccines for malaria.

In the ParaFrap project, we will explore the signaling mechanisms involved in apical organelle secretion during host cell invasion. In particular we will study the role of second messengers including calcium and cyclic nucleotides, cAMP and cGMP, in regulating microneme secretion. A combination of molecular genetics and phosphoproteomic approaches will be used to decipher the signaling pathways responsible for microneme and rhoptry secretion. In addition, we will identify the critical parasite ligands involved in RBC invasion and try to identify combinations of parasite ligands that can be targeted with antibodies to synergistically block invasion with high efficiency. Such combinations will be developed as blood stage vaccines for P. falciparum malaria. Similar approaches will also be attempted with P. vivax for which short term in vitro invasion assays will be established using enriched reticulocytes and cryopresrved blood stage P. vivax isolates.

Top 5 publications of the last 5 years

1. Singh P., Alaganan A., More K. R., Lorthiois, A, Thiberge S Gorgette O., Guillotte Blisnick M., Guglielmini J., Aguilera S. S., Touqui L., Singh S., Chitnis CE. 2019. Role of a patatinlike phospholipase in Plasmodium falciparum gametogenesis and malaria transmission. Proc. Natl. Acad. Sci., USA. DOI 10.1073/pnas.1900266116.

2. Singh K, Mukherjee P, Shakri AR, Singh A, Pandey GC, Bakshi M, Uppal G, Jena R, Rawat A, Kumar P, Bhardwaj R, Yazdani SS, Hans D, Mehta S, Srinivasan A, Anil K, Madhusudhan RL Patel J, Singh A, Rao R, Gangireddy S, Patil R, Kaviraj S, Singh S, Carter D, Reed S, Kaslow DC, Birkett A, Chauhan VS, Chitnis CE. 2018. A malaria vaccine candidate based on Duffy binding protein elicits strain transcending functional antibodies in a Phase I clinical trial. NPJ Vaccines. 3:48. DOI 10.1038/s41541-018-0083-3.

3. Gupta S, Singh S, Popovici J, Roesch C, Shakri AR, Guillotte-Blisnick M, Huon C, Menard D, Chitnis CE. 2018. Targeting a reticulocyte binding protein and Duffy binding protein to inhibit reticulocyte invasion by Plasmodium vivax. Sci Rep. 8(1):10511. DOI 10.1038/s41598-018-28757-4.

4. Chitnis CE, Mukherjee P, Mehta S, Yazdani SS, Dhawan S, Shakri AR, Bhardwaj R, Gupta PK, Hans D, Mazumdar S, Singh B, Kumar S, Pandey G, Parulekar V, Imbault N, Shivyogi P, Godbole G, Mohan K, Leroy O, Singh K, Chauhan VS. 2015. Phase I clinical trial of a recombinant blood stage vaccine candidate for Plasmodium falciparum malaria based on MSP1 and EBA175. PLoS One. 10(4):e0117820. DOI doi.org/10.1371/journal.pone.0117820

5. Dawn A, Singh S, More KR, Siddiqui FA, Pachikara N, Ramdani G, Langsley G, Chitnis CE. The central role of cAMP in regulating Plasmodium falciparum merozoite invasion of human erythrocytes. 2014. PLoS Pathogens. 10(12):e1004520. DOI doi.org/10.1371/journal.ppat.1004520