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- A new regulator of stemness to create dendritic cell factories for immunotherapy
- Advanced methods for genomic rearrangement detection
- Control of cytokine signaling by SOCS1
- Defining the protein modifications associated with respiratory disease
- Delineating the pathways driving cancer development and therapy resistance
- Developing a new drug that targets plasmacytoid dendritic cells for the treatment of lupus
- Development and mechanism of action of novel antimalarials
- Development of a novel particle-based malaria vaccine
- Development of tau-specific therapeutic and diagnostic antibodies
- Discovering novel therapies for major human pathogens
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- Epigenetic biomarkers of tuberculosis infection
- Essential role of glycobiology in malaria parasites
- Evolution of haematopoiesis in vertebrates
- Human lung protective immunity to tuberculosis
- Identifying novel treatment options for ovarian carcinosarcoma
- Interaction with Toxoplasma parasites and the brain
- Interactions between tumour cells and their microenvironment in non-small cell lung cancer
- Investigating the role of mutant p53 in cancer
- Microbiome strain-level analysis using long read sequencing
- Minimising rheumatic adverse events of checkpoint inhibitor cancer therapy
- Modelling spatial and demographic heterogeneity of malaria transmission risk
- Naturally acquired immune response to malaria parasites
- Predicting the effect of non-coding structural variants in cancer
- Structural basis of catenin-independent Wnt signalling
- Structure and biology of proteins essential for Toxoplasma parasite invasion
- T lymphocytes: how memories are made
- TICKER: A cell history recorder for longitudinal patient monitoring
- Targeting host pathways to develop new broad-spectrum antiviral drugs
- Targeting post-translational modifications to disrupting the function of secreted proteins
- Targeting the epigenome to rewire pro-allergic T cells
- Targeting the immune microenvironment to treat KRAS-mutant adenocarcinoma
- The E3 ubiquitin ligase Parkin and mitophagy in Parkinson’s disease
- The molecular controls on dendritic cell development
- Understanding malaria infection dynamics
- Understanding the genetics of neutrophil maturation
- Understanding the neuroimmune regulation of innate immunity
- Understanding the proteins that regulate programmed cell death at the molecular level
- Using cutting-edge single cell tools to understand the origins of cancer
- When healthy cells turn bad: how immune responses can transition to lymphoma
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Oliver Sieber-Projects
Researcher:
Discovery of inherited variants affecting bowel cancer risk and progression
As a member of the international COGENT (COlorectal cancer GENeTics) consortium we are participating in genome-wide association (GWA) studies to identify inherited variants underlying bowel cancer susceptibility. Ongoing GWA analyses are focusing on improving statistical methodologies to identify causal variants, detecting interactions between risk alleles, subgroup analyses and incorporating non-genetic risk factors into risk models. Analogously, inherited variation might play a critical role in determining the natural course of the disease, perhaps by influencing tumour molecular evolution. We are working on linking GWA data to tumour molecular and clinical characteristics to test for the existence of inherited variants influencing bowel cancer progression.
Identification of clinically-relevant molecular subtypes of bowel cancer
Understanding the molecular pathology of bowel cancer is essential for predicting tumour clinical behaviour, for guiding treatment and for the development of new targeted therapies. Next-generation sequencing and microarray technologies provide the opportunity to comprehensively profile the genetic and epigenetic alterations of cancer genomes. We are applying these technologies in community and clinical trial patient cohorts to identify clinically-relevant tumour molecular subtypes, genomic signatures of outcome and principal driver genes. Clinical diagnostics development is being pursued in collaboration with industry partners. New therapeutic opportunities tailored to tumour molecular make-up are being developed using high-content compound screening approaches on patient-derived bowel cancer cell lines.
Study of the molecular mechanisms of bowel cancer progession
Genomics studies are uncovering an increasing number of novel candidate cancer genes for bowel cancer. Some of these candidates will be clinically important driver genes contributing to tumourigenesis and malignant progression, whilst others will be neutral passengers. To systematically identify key driver genes, we are conducting high-throughput candidate knock-down screens for cell viability and migration using a panel of bowel cancer cell lines representing the molecular subtypes of the disease. Lead candidates supported by high-throughput screening results are being taken forward in expanded tailored functional studies in vitro and in vivo to demonstrate their pathogenicity.
High-throughput discovery of new drug combinations for metastatic bowel cancer
Treatment outcomes for patients with metastatic bowel cancer remain poor, with most tumours developing resistance within 24 months. A key problem is that cancers are genetically diverse, with some cells inevitably resistant to any given treatment. Combining drugs targeting distinct essential cellular functions is the principal strategy to overcome this problem, but developing such combinations in the clinic is challenging given the number of agents. We are utilising robotics to test drugs representing the human pharmacopeia in pairwise combinations on human bowel cancer cell lines capturing the genetic diversity of the disease. Lead drug combinations are being progressed for clinical development.