Photini Sinnis, M.D., Ph.D.
Professor at Johns Hopkins Bloomberg School of Public Health
"Establishment of Malaria Infection: Parasite Bottleneck and Point for Intervention"
Photini Sinnis is a professor at the Johns Hopkins Bloomberg School of Public Health. The Sinnis laboratory studies the sporozoite stage of Plasmodium, the infective stage of the malaria parasite. Sporozoites make an impressive journey, from the midgut wall of the mosquito where they emerge from oocysts, to their final destination in the mammalian liver. Using classic biochemistry, mutational analysis, and in vitro and in vivo assays, we aim to elucidate the molecular interactions between the parasite and its mosquito and mammalian hosts that make this journey possible.
The Sinnis laboratory is part of the Johns Hopkins Malaria Research Institute, committed to the pursuit of basic science research that translates into solutions targeting one of the most important infectious diseases in the world. Malaria, caused by protozoan parasites of the genus Plasmodium, is transmitted to humans by infected Anopheles mosquitoes. The evolution of drug resistance by the parasite, and insecticide resistance by the mosquito, have created an urgent need for new strategies to control and ultimately eliminate malaria.
We focus on the transmission of sporozoites from mosquito to mammalian host and how these parasites overcome physical and immunological obstacles to establishing infection. Sporozoites, the infective stage of the malaria parasite, make an impressive journey from the midgut wall of the mosquito where they emerge from oocysts, to their final destination in the mammalian liver (see picture below). Using biochemical, cell biological and genetic approaches, as well as intravital imaging, we aim to understand the molecular interactions between sporozoites and their mosquito and mammalian hosts that enable the parasite to initiate infection.
- Shears MJ, Nirujogi RS, Swearingen KE, Renuse S, Mishra S, Reddy PJ, Moritz RL, Pandey A, Sinnis P. Proteomic Analysis of Plasmodium Merosomes: The Link between Liver and Blood Stages in Malaria. Journal of Proteome Research 2019, 18(9), 3404-3418
- Flores-Garcia Y*, Nasir G*, Hopp CS, Munoz C, Balaban AE, Zavala F, & Sinnis P. Antibody-Mediated Protection against Plasmodium Sporozoites Begins at the Dermal Inoculation Site. mBio, 9(6), e02194-18, 2018 Publication selected for commentary “Shedding Light on the Role of the Skin in Vaccine-Induced Protection against the Malaria Sporozoite” by J.P. Daily, mBio.02555-18
- Hopp CS*, Bennett BL*, Mishra S, Lehmann C, Hanson KK, Lin JW, Rousseau K, Carvalho FA, van der Linden WA, Santos NC, Bogyo M, Khan SM, Heussler V, Sinnis P. Deletion of the rodent malaria ortholog for falcipain-1 highlights differences between hepatic and blood stage merozoites. PLoS Pathog 13:e1006586, 2017.
- Swearingen KE*, Lindner SE*, Shi L, Shears MJ, Harupa A, Hopp CS, Vaughan AM, Springer TA, Moritz RL, Kappe SH, Sinnis P. Interrogating the Plasmodium Sporozoite Surface: Identification of Surface-Exposed Proteins and Demonstration of Glycosylation on CSP and TRAP by Mass Spectrometry-Based Proteomics. PLoS Pathog 12:e1005606, 2016.
- Hopp CS, Chiou K, Ragheb DR, Salman A, Khan SM, Liu AJ, Sinnis P. Longitudinal analysis of Plasmodium sporozoite motility in the dermis reveals component of blood vessel recognition. Elife 4:doi:10.7554/eLife.07789, 2015. Publication selected for commentary “Looking for Blood” by P. Formaglio and R. Amino, Elife 4:2015.