Parasitology Seminar Series
Title: "Eph Receptors: critical molecules in the pathogenesis of malaria"
Speaker: Tracey Lamb, PhD
Assistant Professor, Pathology
University of Utah School of Medicine
Date: September 23, 2019
Time: 12-1 pm
132 Hill Pavilion
University of Pennsylvania School of Veterinary Medicine
380 S University Avenue, Philadelphia, PA 19104
Eph receptors are the largest family of receptor tyrosine kinases (RTKs) and mediate a myriad of essential processes in humans from embryonic development to adult tissue homeostasis through interactions with membrane-bound ephrin ligands. Recent work from my laboratory has demonstrated a critical role of this family of molecules in the pathogenesis of malaria. We have determined that members of the Eph receptor family are involved in immune cell trafficking and vascular activation during infection with Plasmodium parasites leading to vascular leakage and organ damage in this disease. Using mouse models we show that blocking these molecules can help ameliorate the pathogenesis of malaria, and therefore these molecules are novel therapeutic targets for malaria.
"As a postdoctoral Career Development Fellow at the National Institute of Medical Research in London, UK, I specialized in malaria immunology under the auspices of Dr. Jean Langhorne, using thePlasmodium chabaudi mouse model to examine how the inflammatory immune response is regulated. I also investigated the relative contributions of parasite replication and the immune response to malarial anemia. Now I have over 15 years of experience using mouse models of malaria and my lab is simultaneously undertaking parallel research into human malaria in collaboration with Lawrence Ayong and Carole Eboumbou at the Centre du Pasteur, Cameroon, Central Africa. I now have been appointed as an adjunct scientist at this Institute (2017) as well as Adjunct Professor at the University of Yaounde I (2018) where I co-direct the graduate level “Yaounde Advanced Course in Immunology”.
Currently a large focus of my research is determining how the Eph receptor / ephrin ligand family of molecules mediates the pathogenesis of malaria. We are the first to identify the Eph receptor family of molecules as being important in cell trafficking leading to organ-specific pathologies associated with Plasmodium infections. Eph receptors the largest family of receptor tyrosine kinases in humans and EphB2 is critical for the trafficking of fibrogenic macrophages to the liver during malaria infection (Mimche et al., 2015, Hepatology), as well in response to other insults (Mimche et al., 2018, Scientific Reports). Our data also demonstrates that EphA2 is a critical mediator of T cell trafficking to the brain during cerebral malaria (Darling et al., manuscript under revision) and is required for vascular activation and disruption of the blood brain barrier, a hallmark of cerebral malaria. Given the critical role for antibodies in controllingPlasmodium-infected red blood cells we are also examining the recently discovered role of the ephrin B1 molecules in T follicular helper cell function. We have also recently made the discovery that co-infection with gamma herpes viruses can suppress T follicular helper cell function in turn abrogating anti-malaria humoral responses to incoming malaria infections underlining the impact that co-infecting pathogens have on T cell function during malaria infection. Lastly my lab has recently been funded to develop a probiotic-based approach to activating T cell responses that we hope to apply to novel anti-malarial T cell-based approaches such as vaccination.