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- A multi-pronged approach to targeting myeloproliferative neoplasms
- A new paradigm of machine learning-based structural variant detection
- A whole lot of junk or a treasure trove of discovery?
- Advanced imaging interrogation of pathogen induced NETosis
- Analysing the metabolic interactions in brain cancer
- Atopic dermatitis causes and treatments
- Boosting the efficacy of immunotherapy in lung cancer
- Building a cell history recorder using synthetic biology for longitudinal patient monitoring
- Characterisation of malaria parasite proteins exported into infected liver cells
- Deciphering the heterogeneity of the tissue microenvironment by multiplexed 3D imaging
- Defining the mechanisms of thymic involution and regeneration
- Delineating the molecular and cellular origins of liver cancer to identify therapeutic targets
- Developing computational methods for spatial transcriptomics data
- Developing drugs to block malaria transmission
- Developing models for prevention of hereditary ovarian cancer
- Developing statistical frameworks for analysing next generation sequencing data
- Development and mechanism of action of novel antimalarials
- Development of novel RNA sequencing protocols for gene expression analysis
- Discoveries in red blood cell production and function
- Discovering epigenetic silencing mechanisms in female stem cells
- Discovery and targeting of novel regulators of transcription
- Dissecting host cell invasion by the diarrhoeal pathogen Cryptosporidium
- Dissecting mechanisms of cytokine signalling
- Doublecortin-like kinases, drug targets in cancer and neurological disorders
- Epigenetic biomarkers of tuberculosis infection
- Epigenetics – genome wide multiplexed single-cell CUT&Tag assay development
- Exploiting cell death pathways in regulatory T cells for cancer immunotherapy
- Exploiting the cell death pathway to fight Schistosomiasis
- Finding treatments for chromatin disorders of intellectual disability
- Functional epigenomics in human B cells
- How do nutrition interventions and interruption of malaria infection influence development of immunity in sub-Saharan African children?
- Human lung protective immunity to tuberculosis
- Improving therapy in glioblastoma multiforme by activating complimentary programmed cell death pathways
- Innovating novel diagnostic tools for infectious disease control
- Integrative analysis of single cell RNAseq and ATAC-seq data
- Interaction with Toxoplasma parasites and the brain
- Interactions between tumour cells and their microenvironment in non-small cell lung cancer
- Investigation of a novel cell death protein
- Malaria: going bananas for sex
- Mapping spatial variation in gene and transcript expression across tissues
- Mechanisms of Wnt secretion and transport
- Multi-modal computational investigation of single-cell communication in metastatic cancer
- Nanoparticle delivery of antibody mRNA into cells to treat liver diseases
- Naturally acquired immune response to malaria parasites
- Organoid-based discovery of new drug combinations for bowel cancer
- Organoid-based precision medicine approaches for oral cancer
- Removal of tissue contaminations from RNA-seq data
- Reversing antimalarial resistance in human malaria parasites
- Role of glycosylation in malaria parasite infection of liver cells, red blood cells and mosquitoes
- Screening for novel genetic causes of primary immunodeficiency
- Single-cell ATAC CRISPR screening – Illuminate chromatin accessibility changes in genome wide CRISPR screens
- Spatial single-cell CRISPR screening – All in one screen: Where? Who? What?
- Statistical analysis of single-cell multi-omics data
- Structural and functional analysis of epigenetic multi-protein complexes in genome regulation
- Structural basing for Wnt acylation
- Structure, dynamics and impact of extra-chromosomal DNA in cancer
- Targeted deletion of disease-causing T cells
- Targeting cell death pathways in tissue Tregs to treat inflammatory diseases
- The cellular and molecular calculation of life and death in lymphocyte regulation
- The role of hypoxia in cell death and inflammation
- The role of ribosylation in co-ordinating cell death and inflammation
- Understanding Plasmodium falciparum invasion of red blood cells
- Understanding cellular-cross talk within a tumour microenvironment
- Understanding the genetics of neutrophil maturation
- Understanding the roles of E3 ubiquitin ligases in health and disease
- Unveiling the heterogeneity of small cell lung cancer
- Using combination immunotherapy to tackle heterogeneous brain tumours
- Using intravital microscopy for immunotherapy against brain tumours
- Using nanobodies to understand malaria invasion and transmission
- Using structural biology to understand programmed cell death
- Validation and application of serological markers of previous exposure to malaria
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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.