Keynote Speaker 

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"

Biography

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. 

Research Description

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.

Selected Publications

Sinnis Publications

1. 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
2. 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
3. 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.
4. 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.
5. 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.

Opening Speaker

Keke Fairfax, Ph.D.

Assistant Professor, Microbiology and Immunology, Department of Pathology, University of Utah

Research Description

The Fairfaix lab studies IL-4 and immuno-modulation are hallmarks of parasitic infections, my laboratory broadly focuses on using the helminth parasite Schistosoma mansoni as a tool to understand both, the consequences of IL-4 induced immuno-modulation, and the complex interplay between B, T and stromal cells necessary to develop an optimal T and B cell memory response Under this umbrella we currently have three main projects: 1) Understanding the immunological implications of maternal schistosomiasis; 2) Dissecting the role of IL-4 in shaping the cellular environment of peripheral lymph nodes during homeostasis and antigenic challenge; 3) Delineating the mechanistic role of hepatic macrophages in helminth-induced protection from metabolic diseases.

Selected Publications

Dr. Fairfax selected Publications

1. Cortes-Selva, D., A. F. Elvington, A. Ready, B. Rajwa, E. J. Pearce, G. J. Randolph and K. C. Fairfax (2018). "Schistosoma mansoni Infection-Induced Transcriptional Changes in Hepatic Macrophage Metabolism Correlate With an Athero-Protective Phenotype." Frontiers in Immunology 9 (2580).  https://doi.org/10.3389/fimmu.2018.02580

2. Wang F, Johnson RL, DeSmet ML, Snyder PW, Fairfax KC, Fleet JC. Vitamin D Receptor-Dependent Signaling Protects Mice From Dextran Sulfate Sodium-Induced Colitis.Endocrinology. 2017 Jun 1;158(6):1951-1963. doi: 10.1210/en.2016-1913. PubMed PMID: 28368514; PubMed Central PMCID: PMC5460931.

3. Fairfax KC, Everts B, Amiel E, Smith AM, Schramm G, Haas H, Randolph GJ, Taylor JJ, Pearce EJ. IL-4-Secreting Secondary T Follicular Helper (Tfh) Cells Arise from Memory T Cells, Not Persisting Tfh Cells, through a B Cell-Dependent Mechanism.J Immunol. 2015 Feb 23. pii: 1401225. PubMed PMID: 25712216.

4. Fairfax KC, Everts B, Smith AM, Pearce EJ. Regulation of the development of the hepatic B cell compartment during Schistosoma mansoni infection. J Immunol. 2013 Oct 15;191(8):4202-10. doi: 10.4049/jimmunol.1301357. Epub 2013 Sep 13. PubMed PMID: 24038090; PubMed Central PMCID: PMC3851305.

5. Fairfax KC, Amiel E, King IL, Freitas TC, Mohrs M, Pearce EJ. IL-10R blockade during chronic schistosomiasis mansoni results in the loss of B cells from the liver and the development of severe pulmonary disease. PLoS Pathog. 2012 Jan;8(1):e1002490. doi: 10.1371/journal.ppat.1002490. Epub 2012 Jan 26. PubMed PMID: 22291593; PubMed Central PMCID: PMC3266936.

Schedule of Event

Schedule subject to change