Graduate Research Prize Winner 2016
I completed my undergraduate Masters in Molecular and Cellular Biochemistry at the University of Oxford. In my final year, I focused on my two main areas of interest: human genetics and the immune system. During my research project in the laboratory of Professor Julian Knight, I received excellent training in molecular biology techniques that I used to study the phenomenon of endotoxin tolerance in healthy individuals.
In 2010, I was awarded a Prize studentship from the Nuffield Department of Medicine to pursue my DPhil research in the Knight group. I decided to move towards translational research by concentrating on patient cohorts. I investigated the genetic determinants of variation in the human response to both common and rare infection, focusing on sepsis, influenza and common variable immunodeficiency disorders.
The sepsis study in particular was challenging, with a cohort of patients recruited from over 30 participating sites across the UK. I led and coordinated all stages necessary for the generation of the datasets from experimental design to working with interdisciplinary teams including clinicians and research nurses establishing patient recruitment, sample collection, sample extraction, quality control and the implementation of innovative bioinformatics methods for data analysis. I rapidly acquired new skills as a computational genomic researcher. The cohort now consists of over 1,000 patients with severe sepsis for whom peripheral blood leukocytes are available for functional genomic profiling together with plasma, DNA, urine and detailed clinical phenotyping. This is the largest established adult sepsis cohort to date worldwide and a unique resource.
My key discovery was the determination of a gene expression signature, identifying individuals with an immunosuppressed phenotype associated with higher early mortality. I replicated these findings by defining a predictive gene set and then analysing an independent cohort recruited through the same study, leading to a first author publication in The Lancet Respiratory Medicine. This was immensely rewarding, as sepsis remains a potentially life-threatening condition triggered by an infection or injury.
I have presented my doctoral research at international conferences, funded by several travel grants. Upon completion of my DPhil I was awarded MRC DTP Supplementary Funding for four months post-doctoral research in the Knight group to maximize the output from my DPhil.
In addition to my research I am interested in public engagement with science and outreach in schools. I have been proactive in representing the department in its promotional video material, at science festivals and careers events in schools. I particularly enjoyed a number of opportunities to teach including undergraduate college tutorials and the supervision of Masters and DPhil students.
Conducting my DPhil research in the Nuffield Department of Medicine was a great experience and I received excellent mentoring from my supervisor and collaborators. I was inspired to remain in science and I am currently continuing my research career as a postdoctoral research fellow at Harvard Medical School and the Broad Institute in Professor Soumya Raychaudhuri's group. I am interested in how genetics can be used to understand the mechanism of action of drugs and therefore improve the treatment of patients, the overarching strategy in developing precision medicine. I am investigating whether the administration of a drug alters the relationship between genomic variation and gene expression in a cohort of patients with systemic lupus erythematosus.
Davenport EE, Burnham KL, Radhakrishnan J, Humburg P, Hutton P, Mills TC, Rautanen A, Gordon AC, Garrard C, Hill AVS, Hinds CJ and Knight JC (2016). Genomic landscape of the individual host response and outcomes in sepsis: a prospective cohort study. Lancet Respiratory Medicine 4, 259-271
Dhalla F, Fox H, Davenport EE, Sadler R, Anzilotti C, van Schouwenburg PA, Ferry B, Chapel H, Knight JC and Patel S (2016). Chronic Mucocutaneous Candidiasis: characterization of a family with STAT1 gain-of-function and development of an ex vivo assay for Th17 dysfunction of diagnostic utility. Clinical and Experimental Immunology 184, 216-227
van Schouwenburg PA1, Davenport EE1, Kienzler A-K, Marwah I, Wright B, Lucas M, Malinasuskas T, Martin HC, WGS500 Consortium, Lockstone HE, Cazier J-B, Chapel HM, Knight JC and Patel SY (2015). Application of whole genome and RNA sequencing to investigate the genomic landscape of common variable immunodeficiency. Clinical Immunology 160, 301-314
Taylor JC, Martin HC, ...Davenport EE (28/110)... Donnelly P and McVean G (2015) Factors influencing success of clinical genome sequencing across a broad spectrum of disorders. Nature Genetics 47, 717-726
Davenport EE1, Antrobus RD1, Lillie PJ, Gilbert S and Knight JC (2015). Transcriptomic profiling facilitates classification of response to influenza challenge. Journal Molecular Medicine 93, 105-114
Rautanen A, ...Davenport EE (10/38)... Hill AV and Hinds CJ (2015). Genome-wide association study of survival from sepsis due to pneumonia: an observational cohort study. Lancet Respiratory Medicine 3, 53-60
Fairfax BP, Davenport EE, Makino S, Hill AVS, Vannberg FO, Knight JC (2011). A common haplotype of the tumour necrosis factor receptor 2 gene modulates endotoxin tolerance. Journal of Immunology 186, 3058-3065
1 Co-first authors