The Sinnis Laboratory studies the sporozoite stage of Plasmodium, the causative agent of malaria. The impressive journey of sporozoites, from the midgut wall of the mosquito where they emerge from oocysts, to their final destination in the mammalian liver, is the major focus of our investigations. Using classic biochemistry, mutational analysis, intravital imaging, and other assays that we and others have developed, we aim to understand the molecular interactions between sporozoites and their mosquito and mammalian hosts that lead to the establishment of malaria infection.
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. 2017 PMID: 28922424.
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. 2016 PMID: 27128092.
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. 2015 PMID: 26271010.
Ejigiri I, Ragheb DR, Pino P, Coppi A, Bennett BL, Soldati-Favre D, Sinnis P. Shedding of TRAP by a rhomboid protease from the malaria sporozoite surface is essential for gliding motility and sporozoite infectivity. PLoS Pathog. 2012 PMID: 22911675.
Coppi A, Natarajan R, Pradel G, Bennett BL, James ER, Roggero MA, Corradin G, Persson C, Tewari R, Sinnis P. The malaria circumsporozoite protein has two functional domains, each with distinct roles as sporozoites journey from mosquito to mammalian host. J Exp Med. 2011 PMID: 21262960.
Coppi A, Tewari R, Bishop JR, Bennett BL, Lawrence R, Esko JD, Billker O, Sinnis P. Heparan sulfate proteoglycans provide a signal to Plasmodium sporozoites to stop migrating and productively invade host cells. Cell Host Microbe. 2007 PMID: 18005753.