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About

Our research focuses on how the response of innate immune cells which engulf the tuberculosis bacteria, namely macrophages and neutrophils, is dysregulated by known TB risk factors and viral co-infection with HIV-1 and SARS-CoV-2.

We combine analysis of clinical cohort samples to identify novel pathways of pathogenesis in humans, with in vitro models of TB, HIV and SARS-CoV-2 infection to determine the molecular mechanism underlying disease risk.

This includes genetic and epigenetic changes in both the host and bacteria and how these impact the inflammatory response during infection. We are particularly interested in the regulation of various cell death pathways and the heterogeneity of cellular responses which we probe with single cell techniques and advanced live cell imaging.

We are currently screening small molecule inhibitors to target various pathways of interest which we hope to develop into new preventative treatments for TB. We also conduct biomarker discovery in at-risk populations using whole genome RNAseq and DNA methylation analysis to identify novel blood-based diagnostics for identifying individuals infected and at risk of disease.

Our goal is to develop a screening tool we can use to identify infected people who will have the greatest benefit from these new preventive therapies, based on their own individual risk profile.

Publications

Selected publications from Dr Anna Coussens

Sheerin D, Abhimanyu A, Wang X, Johnson WE, Coussens AK. Immunopathogenic Overlap and Shared Therapeutic Targets for Covid-19 and Tuberculosis Predicted from Transcriptomic Meta-Analysis. Cell Rep Med. 2021; Sneak peak [https://papers.ssrn.com/sol3/papers.cfm?abstract_id=3815987]

Waters R, Ndengane M, Abrahams MR, Diedrich CR, Wilkinson RJ, Coussens AK. The Mtb-HIV syndemic interaction: why treating M. tuberculosis infection may be crucial for HIV-1 eradication. Future Virol. 2020 Feb;15(2):101-125. doi: 10.2217/fvl-2019-0069. PMID: 32273900

Seddon JA, Chiang SS, Esmail H, Coussens AK. The Wonder Years: What Can Primary School Children Teach Us about Immunity to Mycobacterium tuberculosis? Front Immunol. 2018 Dec 3;9:2946 PMID: 30619306

Scriba T, Coussens AK, Fletcher H. Human Immunology of Tuberculosis. In Tuberculosis and the Tubercle Bacillus, ed. McShane H, Jacobs WR, Mizrahi V, Orme IM, ASM Press. 2017 Feb; doi: 10.1128/microbiolspec.TBTB2-0016-2016 ISBN: 9781555819552 PMID: 27740453

Coussens AK, Mason PH, Oni T. Socio-political prescriptions for LTBI are required to prevent re-activation of TB. Int J Infect Dis. 2017 May;58:115-116. PMID: 28161463
Esmail H, Lai RP, Lesosky M, Wilkinson KA, Graham CM, Coussens AK, Oni T, Warwick JM, Said-Hartley Q, Koegelenberg CF, Walzl G, Flynn JL, Young DB, Barry CE 3rd, O’Garra A, Wilkinson RJ. [18F]-fluorodeoxyglucose combined positron emission and computed tomographic characterisation of progressive HIV-associated tuberculosis. Nat Med. 2016 Oct;22(10):1090-1093. PMID: 27595321

Coussens AK, Wilkinson RJ, Martineau AR. Phenylbutyrate is bacteriostatic against Mycobacterium tuberculosis and regulates the macrophage response to infection, synergistically with 25-hydroxy-vitamin D3. PLOS Pathog. 2015 Jul 2;11(7):e1005007. PMID: 26133770

Coussens AK, Naude C, Goliath R, Chaplin G, Wilkinson RJ, Jablonski N. High-dose vitamin D3 reduces deficiency due to low UVB exposure and limits HIV replication in urban Southern Africans. Proc Natl Acad Sci U S A. 2015 Jun 30;112(26):8052-7. PMID: 26080414

Coussens AK, Wilkinson RJ, Nikolayevskyy V, Elkington PT, Hanifa Y, Islam K, Timms PM, Bothamley GH, Claxton AP, Packe GE, Darmalingam M, Davidson RN, Milburn HJ, Baker LV, Barker RD, Drobniewski FA, Mein CA, Bhaw-Rosun L, Nuamah R, Griffiths CJ, Martineau AR. Ethnic variation in inflammatory profile in tuberculosis. PLoS Pathog. 2013 Jul 4;9(7):e1003468. PMID: 23853590

Coussens AK, Wilkinson RJ, Hanifa Y, Nikolayevskyy V, Elkington PT, Islam K, Timms PM, Venton TR, Bothamley GH, Packe GE, Darmalingam M, Davidson RN, Milburn HJ, Baker LV, Barker RD, Mein CA, Bhaw-Rosun L, Nuamah R, Young DB, Drobniewski FA, Griffiths CJ, Martineau AR. Vitamin D accelerates resolution of inflammatory responses during tuberculosis treatment. Proc Natl Acad Sci U S A. 2012 Sep 18;109(38):15449-54. PMID: 22949664

Lab research projects

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