Dr Jaishree Tripathi

Research Interest

Infectious diseases still contribute significantly to the global burden of death and disability, with malaria being one of the top killers. Despite numerous malaria control strategies developed and implemented worldwide, current frontline treatment with artemisinin combination therapies (ACT) is starting to fail and the only approved vaccine for malaria (RTS,S/AS01) shows limited efficacy of < 50 % in naturally infected individuals. One of the major challenges in effective vaccine development is parasite antigen diversity (i.e. several vaccine candidates are highly polymorphic and highly variable) and redundancy. Transcriptomics approaches are often applied to explore the developmental stage-specific expression of potentially targetable parasite antigens, with insight into splice variants and identification of polymorphic genes. Dr. Tripathi’s research focuses on applying state-of-the-art single cell RNA sequencing approaches to investigate transcriptional heterogeneity and stochastic gene expression in Plasmodium spp. Our research findings revealed significant transcriptional variability between individual P. falciparum parasites with transcriptomically distinct sub-populations being identified, along with a distinct group of highly variable genes uncovered. Stochastic expression of key invasion genes, such as, msp1, msp3, msp7, eba181 and ama1, which represent prime candidates for invasion-blocking vaccines, was identified¹. These results suggest that due to the cell-to-cell variability of expression for most of these antigens might underlay the low efficacies of previous single candidate blood-stage vaccines development strategies, and that new strategies might require targeting several invasion factors simultaneously. Overall these research findings provide future precedence for cross-referencing of single cell transcriptomics data for new malaria intervention strategies. We are currently applying our established methodology to study stochastic gene expression in other human and zoonotic Plasmodium spp. In addition to above research interests, Dr. Tripathi has developed a comprehensive transcriptomics and RNA handling pipeline² to study hallmarks of cellular senescence and drug resilience in dormant P. falciparum asexual stage parasites⁴.

Biography

Dr. Jaishree Tripathi joined the Department of Microbiology and Immunology, Yong Loo Lin School of Medicine, NUS, in 2022 as a Lecturer and has over 11 years of research experience investigating various aspects of malaria parasite biology and host-parasite interactions. Dr. Tripathi applied single cell transcriptomics approaches to study stochastic gene expression in the human malaria parasites Plasmodium falciparum¹ during her postdoctoral research at Nanyang Technological University. In addition, Dr. Tripathi is also interested in understanding mechanisms governing dormancy in asexual blood stage of malaria parasites⁴. Dr. Tripathi graduated from the University of Cambridge in 2015, where she developed stem-cell based models to study host-parasite interactions during the liver stage infection of rodent malaria parasite P. berghei³.

Recent Publications

1. Tripathi J., Zhu L., Nayak S., Stoklasa M., Bozdech Z. (2022). Stochastic Expression of Invasion Genes in Plasmodium falciparum Schizonts. Nature Communications, 13(1):3004.
2. Kucharski M.*, Tripathi J.*, Nayak S., Zhu L. Wirjanata G., van der Pluijm R. W., Dhorda M., Dondorp A. & Bozdech Z. (2020). A Comprehensive RNA Handling and Transcriptomics Guide for High-Throughput Processing of Plasmodium Blood-Stage Samples. Malaria Journal, 19, 363. (* equal contribution)
3. Tripathi, J., Segeritz C. P., Griffiths G., Bushell W., Skarnes W. C., Vallier L., Mota M. M. & Billker O. (2020). A novel chemically differentiated mouse embryonic stem cell model to study liver stages of Plasmodium berghei. Stem Cell Reports, 14,1-12.
4. Tripathi J.*, Stoklasa M.*, Nayak S., Low K.E., Lee E. Q. H., Renia L., Malleret B. and Bozdech Z. (2023). The artemisinin-induced dormant stages of Plasmodium falciparum exhibit hallmarks of cellular senescence and drug resilience. bioRxiv: https://doi.org/10.1101/2023.01.29.526019 (* equal contribution)
5. Zhu L., Tripathi J., Rocamora F. M., Miotto O., Pluijm R., Voss T. S., Mok S., Kwiatkowski D. P., Nosten F., Day N. P. J., White N. J., Dondorp A. M., Bozdech Z. & Tracking Resistance to Artemisinin Collaboration I. (2018). The origins of malaria artemisinin resistance defined by a genetic and transcriptomic background. Nature Communications, 9:5158.
6. Gupta, A.P., Lei Z., Tripathi J., Kucharski M., Patra A. & Bozdech Z. (2017). Histone 4 lysine 8 acetylation regulates proliferation and host-pathogen interaction in Plasmodium falciparum. Epigenetics & Chromatin, 10:40.
7. Varunan, S.M., Tripathi, J., Bhattacharyya, S., Suhane, T. & Bhattacharyya, M.K. (2013). Plasmodium falciparum origin recognition complex subunit 1 (PfOrc1) functionally complements Δsir3 mutant of Saccharomyces cerevisiae. Molecular and Biochemical Parasitology, 191, 28–35
8. Zhu L.*, van der Pluijm R. W.*, Kucharski M.*, Nayak S., Tripathi J., White N. J., Day N. P. J., Faiz A., Phyo A. P., Amaratunga C., Lek D., Ashley E.A., Nosten F., Smithuis F., Ginsburg H., Seidlein L., Lin K., Imwong M., Chotivanich K., Mayxay M., Dhorda M., Nguyen H. C., Nguyen T. N. T., Miotto O., Newton P. N., Jittamala P., Tripura R., Pukrittayakamee S., Peto T. J., , Hien T. T., Dondorp A. M. and Bozdech Z. (2022). Artemisinin resistance in the malaria parasite, Plasmodium falciparum, originates from its initial transcriptional response. Communications Biology, 5, 274.
9. Mok S., Stokes B.H., Gnädig N. F., Ross L. S., Yeo T., Amaratunga C., Allman E., Solyakov L., Bottrill A. R., Tripathi J., Fairhurst R., Llinás M., Bozdech Z., Tobin A. B., Fidock D. A. (2021). Artemisinin-Resistant K13 Mutations Rewrite Plasmodium falciparum’s Intra-Erythrocytic Development and Alter Mitochondrial Physiology. Nature Communications, 12, 530.
10. Naidu R., Chu T.T.T., Tripathi J. , Hu Y., Subramanian G., Tong J. X., Tripathi P., Fang K., Tan K. S. W., Lim C. T., Chan J. K. Y., Bozdech Z. and Chandramohanadas R. (2019). Reticulocyte Infection Leads to Altered Behaviour, Drug Sensitivity and Host Cell Remodelling by Plasmodium falciparum. bioRxiv: https://doi.org/10.1101/862169