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. Martinez FJ, White M, Guillotte-Blisnick M, Huon C, Boucharlat A, Agou F, England P, Popovici J, Hou MM, Silk SE, Barrett JR, Nielsen CM, Reimer JM, Mukherjee P, Chauhan VS, Minassian AM, Draper SJ, Chitnis CE. 2024. PvDBPII elicits multiple antibody-mediated mechanisms that reduce growth in a Plasmodium vivax challenge trial. NPJ Vaccines. 9(1):10. doi: 10.1038/s41541-023-00796-7

2. Bouyssou I, El Hoss S, Doderer-Lang C, Schoenhals M, Rasoloharimanana LT, Vigan-Womas I, Ratsimbasoa A, Abate A, Golassa L, Mabilotte S, Kessler P, Guillotte-Blisnick M, Martinez FJ, Chitnis CE, Strouboulis J, Ménard D. 2023. Unveiling P. vivax invasion pathways in Duffy-negative individuals. Cell Host Microbe. 31(12):2080-2092.e5. doi: 10.1016/j.chom.2023.11.007. 

3. Martinez FJ, Guillotte-Blisnick M, Huon C, England P, Popovici J, Laude H, Arowas L, Ungeheuer MN, Reimer JM, Carter D, Reed S, Mukherjee P, Chauhan VS, Chitnis CE. 2023. Immunogenicity of a Plasmodium vivax vaccine based on the duffy binding protein formulated using adjuvants compatible for use in humans. Sci Rep. 13(1):13904. doi: 10.1038/s41598-023-40043-6. 

4. Hou MM, Barrett JR, Themistocleous Y, Rawlinson TA, Diouf A, Martinez FJ, Nielsen CM, Lias AM, King LDW, Edwards NJ, Greenwood NM, Kingham L, Poulton ID, Khozoee B, Goh C, Hodgson SH, Mac Lochlainn DJ, Salkeld J, Guillotte-Blisnick M, Huon C, Mohring F, Reimer JM, Chauhan VS, Mukherjee P, Biswas S, Taylor IJ, Lawrie AM, Cho JS, Nugent FL, Long CA, Moon RW, Miura K, Silk SE, Chitnis CE, Minassian AM, Draper SJ. 2023. Vaccination with Plasmodium vivax Duffy-binding protein inhibits parasite growth during controlled human malaria infection. Sci Transl Med. 15(704):eadf1782. doi: 10.1126/scitranslmed.adf1782. 

5. Wagner MP, Chitnis CE. Lipid peroxidation and its repair in malaria parasites. Trends Parasitol. 2023 Mar;39(3):200-211. doi: 10.1016/j.pt.2022.12.006. PMID: 36642689.