My research interest lies in integrating functional genomics and clinical data to understand how genetics contributes to patient heterogeneity. I focus on how environmental perturbations modulate the regulation of gene expression in the immune cells of an individual. This can be determined by mapping in vivo expression quantitative trait locus (eQTL) interactions, where an eQTL effect is modulated by the environmental perturbation. Identifying such interactions can give insights into condition dependent regulators of gene expression and therefore insights into disease and drug mechanisms of action.
To explore heterogeneity in treatment response, we developed a statistical framework to investigate how the administration of a drug alters the relationship between genomic variation and gene expression. Through an industry collaboration with Pfizer, we have analysed data from an anti-IL-6 clinical trial in patients with systemic lupus erythematosus. We have identified in vivo eQTL interaction events with IL-6 and IFN, two clinically important cytokines with dramatic variation in this cohort due to therapy and disease status respectively. We find transcription factor binding motifs interrupted by eQTL interaction SNPs, which point to key regulatory mediators of these environmental perturbations.
Through a collaboration with Julian Knight (University of Oxford) we have profiled gene expression to determine disease heterogeneity within a cohort of sepsis patients. A key finding was a gene expression signature stratifying patients into two distinct sepsis response signature (SRS) groups. The SRS1 group identifies individuals with an immunosuppressed phenotype and was associated with higher mortality. We identify in vivo eQTL interactions with SRS group including for a number of transcription factors such as TAF1C, IRF5 and EPAS1.
Emma Davenport is a Group Leader at the Wellcome Sanger Institute, Cambridge. Her group focuses on how genetics contributes to patient-to-patient heterogeneity within disease and in response to treatment. In particular, they use gene expression data to identify subgroup specific signatures and to map in vivo expression quantitative trait locus (eQTL) interactions.
Emma conducted her postdoctoral research in Professor Soumya Raychaudhuri’s lab at Brigham and Women’s Hospital, Harvard Medical School and the Broad Institute. There she developed a statistical framework to investigate how the administration of a drug alters the relationship between genomic variation and gene expression (drug eQTL interactions).
Emma completed her PhD research under the supervision of Professor Julian Knight at the University of Oxford. She investigated the genetic determinants of variation in the human response to common and rare infection, focusing on sepsis and common variable immunodeficiency disorders. A key finding was a gene expression signature stratifying patients into two distinct sepsis response signature (SRS) groups. The SRS1 group identifies individuals with an immunosuppressed phenotype and was associated with higher mortality
