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Research

Surgical resection of cancer remains the frontline therapy for millions of patients annually, but post-operative recurrence is common, with a relapse rate of around 45% for non-small cell lung cancer. The tumour draining lymph nodes (dLN) are resected at the time of surgery for staging purposes, and this cannot be a null event for patient survival and future response to immune checkpoint blockade treatment. This project investigates cancer surgery, lymphadenectomy, onset of metastatic disease, and response to immunotherapy in a novel model that closely reflects the clinical setting. In a murine metastatic lung cancer model, primary subcutaneous tumours were resected with associated dLNs remaining intact, completely resected or partially resected.

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Epigenetics links perinatal influences with later obesity. We identifed differentially methylated CpG (dmCpG) loci measured at 17 years associated with concurrent adiposity measures and examined whether these were associated with hsCRP, adipokines, and early life environmental factors. Genome-wide DNA methylation from 1192 Raine Study participants at 17 years, identified 29 dmCpGs associated with body mass index, 10 with waist circumference and 9 with subcutaneous fat thickness.

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Exome sequencing has enabled molecular diagnoses for rare disease patients but often with initial diagnostic rates of ~25-30%. Here we develop a robust computational pipeline to rank variants for reassessment of unsolved rare disease patients. A comprehensive web-based patient report is generated in which all deleterious variants can be filtered by gene, variant characteristics, OMIM disease and Phenolyzer scores, and all are annotated with an ACMG classification and links to ClinVar.

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Immune checkpoint therapy (ICT) results in durable responses in individuals with some cancers, but not all patients respond to treatment. ICT improves CD8+ cytotoxic T lymphocyte (CTL) function, but changes in tumor antigen-specific CTLs post-ICT that correlate with successful responses have not been well characterized. Here, we studied murine tumor models with dichotomous responses to ICT.

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We identified numerous CpGs differentially methylated in relation to gestational age at birth that appear to reflect fetal developmental processes across tissues

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Here we focus on the problem of prioritising variants with respect to the observed disease phenotype

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Our results identify a pretreatment tumor microenvironment that predicts response to immune checkpoint blockade, which can be therapeutically attained

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Our result highlighted that miRNA-target gene network contributes to human disease genetics in a cell type-specific manner

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Epigenetic changes at the GFI1 were linked to smoking exposure in-utero/in-adulthood and robustly associated with cardio-metabolic risk factors

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A better understanding of the innate immune responses by CF airway epithelial cells is needed to identify why viral infections are more severe in CF