We work on malaria, a disease caused by infection with parasites of the genus Plasmodium. According to the World Malaria Report in 2016 there are over 200 million cases of malaria every year, resulting in approximately 500,000 deaths. Most of these deaths occur in children under 5 years, or in pregnant women. Given that the newly developed RTS,S has a transient and limited protection against Plasmodium infection and malarial disease, much work is still needed to develop novel therapeutics to help combat this disease. Plasmodium parasites invade the body’s red blood cells and can cause a harmful systemic infection.
We work closely with Dr Lawrence Ayong and Dr Carole Eboumbou at the Center du Pasteur Cameroon in Central Africa and use rodent models of malaria to dissect the mechanisms human malarial disease. Work in the Lamb lab spans several research questions:
How do the Eph receptor tyrosine kinase family of molecules mediate pathogenesis of malaria?
Lab members: Thayer King, Patrice Mimche, Tuna Ortiz
Eph receptors are the largest family of tyrosine receptor kinases. We have discovered that these molecules play a central role in mediating a number of pathogenic symptoms in malaria including malaria-associated liver fibrosis and opening of the blood brain barrier during cerebral symptoms of Plasmodium infection. Current work is determining the molecular mechanisms by which these molecules mediate pathogenesis of malaria with a view to designing novel Eph-based therapies for use in malaria.
How do ephrin ligands modulate T cell function in response to Plasmodium infection?
Lab members: Patrice Mimche, Thayer King, Georgia Veverka
Ephrin ligands are expressed on germinal center B cells, as well as on T follicular helper cells during malaria. This work will define the role that these molecules play in modulating adaptive immune responses that control Plasmodium parasitemia.
How does co-infection with other pathogens modulate the pathogenesis of malaria?
Lab member: Palmer Netongo
Most individuals who have malaria are co-infected with other pathogens. In collaboration with Sam Speck’s laboratory at Emory University we are investigating our recent observation that co-infection with acute gammaherpesviruses such as Epstein Barr Virus, suppresses anti-malarial humoral responses leading to the development of severe malaria.
What is the optimal way to deliver subunit vaccines to generate efficacious anti-malarial responses?
Lab members: Pei-Yi Tai, Taryn Stewart
Vaccination to protect against infection is a life-saving concept, made famous by Edward Jenner who used cowpox to protect individuals against smallpox. Recent release of the RTS,S vaccine against malaria showed limited and transient protection against malarial disease in the field, but demonstrated that vaccination against malaria might be possible. One of the challenges to mass vaccination in disease endemic countries is the costly administration by injection. We are developing an oral vaccine delivery system to express and deliver subunit vaccine antigens directly to the mucosal immune system using probiotic yeast. Such a vaccine delivery system would be cost effective to produce and deliver.
References (Selected Publications)
Eph Receptors and Malaria
- Mimche, PN, Brady, LM, Bray, CF, Thapa, M, McDermott, CD, King, TP, Quicke, K, Lee, CM, Mimche, SM, Grakoui, A, Morgan, ET and Lamb TJ (2015) The receptor tyrosine kinase EphB2 contributes to liver fibrosis during mouse malaria infection. Hepatology 62(3): pp900-14 PMID: 25784101
- Mimche, PN, Brady, LM, Bray, CF, Hudson, LE, Fenne DW, Keeton, S, Lamb, TJ. (2015). Expression of the receptor tyrosine kinase EphB2 on dendritic cells is modulated by Toll-like receptor ligation but is not required for T cell activation. PLoS One 10(9): e0138835 PMID: 26407069
Co-Infection and Malaria
- Matar CM, Anthony N, Jacobs N, Priyamvada L, Engwerda C, Speck, SH* and Lamb TJ*(2015). Gammaherpes virus co-infection impairs the generation of anti-malaria immunity turning a non-lethal malaria infection into a lethal one. PLOS pathogens 11(5):e1004858 PMID:25996913 *co-corresponding authors
- Matar CM, Jacobs NT, Speck SH, Lamb TJ* and Moormann A*. (2015) Does Epstein-Barr virus alter the pathogenesis of malaria infection? Parasite Immunology in press PMID: 26121587 *co-corresponding authors
- Abanyie FA, McCracken C, Kirwan P, Molloy SF, Asaolu SO, Holland CV, Gutman J and Lamb TJ (2013). Ascaris co-infection does not alter malaria-induced anaemia in a cohort of Nigerian preschool children. Malaria Journal 12(1): e1. PMID: 23282136
Developing Probiotic Yeast as a Vaccine Expression and Delivery System
- Hudson, LE, Stewart, TP, Fasken, M, Corbett, AH and Lamb, TJ. (2016) Transformation of Probiotic Yeast and their Recovery from Gastrointestinal Immune Tissues Following Oral Gavage in Mice. J Vis Exp 108 PMID: 26890281
- Hudson, LE, McDermott, CD, Stewart, TP, Hudson, WH, Fasken, MB, Corbett, AH and Lamb, TJ. (2016). Characterization of the Probiotic Yeast Saccharomyces boulardii in the Healthy Mucosal Immune System. PLoS One 11(4) e0153351 PMID: 27064465
- Hudson, LE, Fasken, MB, McDermott, CD, Kuiper, EG, Guiliano, DB, Corbett, AH and Lamb, TJ (2014). Functional heterologous protein expression by genetically engineered probiotic yeast Saccharomyces boulardii. PLOS One 9 (11): e112660 PMID: 25391025
- Hudson LE, Anderson SE, Corbett AH, Lamb TJ (2017). Gleaning Insights from Fecal Microbiota Transplantation and Probiotic Studies for the Rational Design of Combination Microbial Therapies. Clinical Microbiology Reviews, 30(1): 191-231. PMID 27856521