Genevieve Martin

Highly Commended in Year 3 Graduate Prize

Genevieve Martin

My fascination with host-pathogen interactions began during high school – and the opportunity to participate in the International Biology Olympiad at this time fuelled my passion for science. I came to Oxford having completed my undergraduate medical degree at Monash University and have worked as a junior doctor in Melbourne, Australia. My DPhil research is supported by a prestigious John Monash Scholarship, a Clarendon Scholarship and the Nuffield Department of Medicine Prize Studentship.

My doctoral research, supervised by John Frater and Chris Willberg, focuses on the relevance of T cell immunity to HIV cure strategies. Whilst antiretroviral therapy is extremely effective at limiting viral replication, this therapy is not curative and must be taken for life. HIV persists in the body during therapy in the HIV reservoir – a pool of cells that contain transcriptionally silent, integrated proviral DNA. Strategies to target this HIV reservoir are being developed, many of which aim to use a boosted immune response to clear the reservoir. I am studying on a type of immune dysfunction known as T cell exhaustion, which develops in chronic viral infections and cancer. Of relevance, the development of exhaustion could limit the utility of immune strategies to target the HIV reservoir.

Our research is conducted within a large observational cohort study of treated primary HIV infection known as HEATHER (HIV Reservoir targeting with Early Antiretroviral Therapy). Within this cohort I am studying the development of T cell exhaustion during primary HIV infection, and the impact of early initiation of antiretroviral therapy on this. We are interested in how T cell exhaustion relates to the size and cellular location of the HIV reservoir, as well as clinical outcomes such as virological remission following treatment interruption.

During my DPhil I have had the opportunity to present my work at several international conferences, and have produced two first author publications. A notable achievement this year was the work I produced on CD32 expression during primary HIV infection which we performed in response to the recent identification by others of this as a novel marker of the HIV reservoir. Using the skills and techniques I had developed over the first two years of the DPhil, I was able to conduct and prepare this research for presentation in a very short timeframe and was subsequently invited to co-author a report on the 2017 IAS Cure and Cancer Forum at which I presented this work.

In the future I would love to have a career that combines research with clinical practice. As an aspiring clinician-researcher I have really valued the opportunity I have had during my DPhil in the NDM to conduct clinically relevant research and I continue to benefit from being surrounded by inspirational clinician-scientists.

Publications

Martin GE, Alcami J, Spano JP, Ross AL (2017), “Converging roads: the latest science from the 2017 IAS HIV Cure and Cancer Forum”, Journal of Virus Eradication, vol 3, e1-e6.

Martin GE, Gossez M, Williams JP, Stöhr W, Meyerowitz J, Leitman EM, Goulder P, Porter K, Fidler S, Frater J and the SPARTAC Trial Investigators (2017), “Post-treatment control or treated controllers? Viral remission in treated and untreated primary HIV infection”, AIDS, 31, pp. 477–484, DOI: 10.1097/QAD.0000000000001382

Hoffmann M*, Pantazis N*, Martin GE*, Hickling S, Hurst J, Meyerowitz J, Willberg CB, Robinson N, Brown H, Fisher M, Kinloch S, Babiker A, Weber J, Nwokolo N, Fox J, Fidler S, Phillips R, Frater J on behalf of the SPARTAC and CHERUB Investigators (2016), “Exhaustion of activated CD8+ T cells predicts disease progression in primary HIV-1 infection, PLoS Pathogens, vol. 2, no. 7, e1005661. DOI:10.1371/journal.ppat.1005661

Martin GE, Pace M, Frater J (2015), “Hidden menace: the key to curing HIV lies in eradicating the reservoir of viruses residing in quiescent immune cells”, The Scientist, vol. 29, no. 5.