Dr Leopold Tientcheu

Country: Gambia

Institution: MRC Unit The Gambia at London School of Tropical Medicine & Hygiene

Research Areas: Immunology, Transcriptomics, Genomics

Lab Website: www.mrc.gm

Tuberculosis (TB) has coevolved with human populations such that the lineages of Mycobacterium tuberculosis complex (MTBC) are closely associated with human migratory pathways. TB and the human response to bacilli are thus closely aligned but may have differed under environmental specific selective pressures. Such differences have important implications for treatment, not only for the use of antibiotics, where ethnicity is a contributor to antibiotic metabolism, but particularly for the development of novel immunotherapeutic for TB, otherwise called host-directed therapeutics (HDTs). My lab aim to correlate the response of West African and South African populations to MTBC lineages with efficacy of HDTs. Our current study will exploit the test case of Gleevec (Imatinib), which augments myeloid response to TB and currently being tested against pulmonary TB in Atlanta and Johannesburg. The plan is to expand to other repurposed HDT drugs for TB currently at pre-clinical stages. We will address this firstly by investigating in-vitro how West African and South African monocytes inhibit the growth of allopatric compared to sympatric MTBC lineages in the absence or presence of candidate HDT molecules and measure the cellular and inflammatory response differences. Secondly, determine the differential gene expression pathways elicited by sympatric versus allopatric MTBC lineages. Thirdly, harness the top expressed genes/pathways to predict the responses to novel HDTs molecules.