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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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Nadia Kershaw - projects
Researcher:
Structure and Function of the Thrombopoietin Receptor
The cytokine Thrombopoietin (Tpo) controls the maintenance of blood stem cells as well as the numbers of platelet in the blood. Clinically, excessive signalling through the molecule that recognises Tpo (the Thrombopoietin Receptor) causes a type of blood cancer called myeloproliferative disease.
The architecture of TpoR is distinct from any other cytokine receptor and there is a complete lack of structural data for it. We have developed a recombinant expression system for Tpo and TpoR, which interact readily and we are using crystallography and CryoEM to solve the structure of the TpoR:TpoR complex. We are also using our unique reagents and structural information to developing novel strategies for inhibiting excessive TpoR signalling, with the aim of generating new treatments for myeloproliferative disease. This work is in collaboration with the Babon Lab (WEHI).
Structural and mechanistic studies on Suppressors of Cytokine Signaling.
The Suppressors of Cytokine Signalling (SOCS) have long been studied at WEHI for their role in negative regulation of cytokine signalling. The Kershaw and Babon Labs have made a significant contribution to basic research in this area, solving the first structures of SOCS1 as the first structures of SOCS1 and SOCS3 bound to the JAK kinase domain. More recently, with the advent of immunotherapy as an exciting treatment option for cancer, inhibiting the SOCS proteins provides a possible route to boost the efficacy of current immunotherapy approaches. We are studying the mechanism of SOCS proteins and other negative regulators of cytokine signaling such as LNK and PTP1B. This work is in collaboration with the Babon Lab (WEHI).
Novel modulators of T-cell activity in autoimmunity and cancer
T cells are a critical part of a healthy immune system, and T-cell activation is one of several key events required to successfully mount an immune response. Soluble CTLA4 proteins block T cell activation, and are already in use as therapeutics for rheumatoid arthritis and organ transplant rejection (e.g Abatacept), but recent publications from several groups indicate the mode of action of current CTLA4-based therapeutics may be more complex that initially thought.
We are exploring novel CTLA4-fusions and their potential as immunomodulatory therapeutics. This project involves rational design of CTLA4 variants with altered immunomodulatory activity, and structural studies on the mode of binding with target proteins, to allow further refinement as therapeutics as well as elucidation of the mode of action. This work is in collaboration with Associate Professor Ross Dickins (Monash).
Resource
Monash University research project: Novel immunosuppressive mechanisms of CTLA4 and CTLA4-Ig therapies