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- A new regulator of 'stemness' to create dendritic cell factories for immunotherapy
- Advanced imaging interrogation of pathogen induced NETosis
- Cancer driver deserts
- Cryo-electron microscopy of Wnt signalling complexes
- Deciphering the heterogeneity of breast cancer at the epigenetic and genetic levels
- Developing drugs to block malaria transmission
- Developing new computational tools for CRISPR genomics to advance cancer research
- Developing novel antibody-based methods for regulating apoptotic cell death
- Discovering novel paradigms to cure viral and bacterial infections
- Discovery and targeting of novel regulators of transcription
- Dissecting host cell invasion by the diarrhoeal pathogen Cryptosporidium
- Do membrane forces govern assembly of the deadly apoptotic pore?
- Doublecortin-like kinases, drug targets in cancer and neurological disorders
- E3 ubiquitin ligases in neurodegeneration, autoinflammation and cancer
- Engineering improved CAR-T cell therapies
- Epigenetic biomarkers of tuberculosis infection
- Exploiting cell death pathways in regulatory T cells for cancer immunotherapy
- Finding treatments for chromatin disorders of intellectual disability
- Functional epigenomics in human B cells
- Genomic rearrangement detection with third generation sequencing technology
- How does DNA damage shape disease susceptibility over a lifetime?
- How does DNA hypermutation shape the development of solid tumours?
- How platelets prevent neonatal stroke
- Human lung protective immunity to tuberculosis
- Interaction with Toxoplasma parasites and the brain
- Interactions between tumour cells and their microenvironment in non-small cell lung cancer
- Investigating the role of dysregulated Tom40 in neurodegeneration
- Investigating the role of mutant p53 in cancer
- Lupus: proteasome inhibitors and inflammation
- Machine learning methods for somatic genome rearrangement detection
- Malaria: going bananas for sex
- Measurements of malaria parasite and erythrocyte membrane interactions using cutting-edge microscopy
- Measuring susceptibility of cancer cells to BH3-mimetics
- Minimising rheumatic adverse events of checkpoint inhibitor cancer therapy
- Mutational signatures of structural variation
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- Predicting the effect of non-coding structural variants in cancer
- Revealing the epigenetic origins of immune disease
- Reversing antimalarial resistance in human malaria parasites
- Structural and functional analysis of DNA repair complexes
- Targeting human infective coronaviruses using alpaca antibodies
- Towards targeting altered glial biology in high-grade brain cancers
- Uncovering the real impact of persistent malaria infections
- Understanding Plasmodium falciparum invasion of red blood cells
- Understanding how malaria parasites sabotage acquisition of immunity
- Understanding malaria infection dynamics
- Understanding the mechanism of type I cytokine receptor activation
- Unveiling the heterogeneity of small cell lung cancer
- Using alpaca antibodies to understand malaria invasion and transmission
- Using combination immunotherapy to tackle heterogeneous brain tumours
- Using intravital microscopy for immunotherapy against brain tumours
- Using nanobodies to cross the blood brain barrier for drug delivery
- Using structural biology to understand programmed cell death
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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.