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- A new regulator of stemness to create dendritic cell factories for immunotherapy
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- Developing a new drug that targets plasmacytoid dendritic cells for the treatment of lupus
- Development and mechanism of action of novel antimalarials
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- 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
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- 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
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- Targeting the epigenome to rewire pro-allergic T cells
- Targeting the immune microenvironment to treat KRAS-mutant adenocarcinoma
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- When healthy cells turn bad: how immune responses can transition to lymphoma
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Gemma Kelly - Projects
Researcher:
Identifying potential resistance factors to BH3 mimetic drugs targeting MCL-1 for cancer therapy
BH3 mimetic drugs aim to trigger cell death for cancer therapy through inhibiting cellular pro-survival proteins of the BCL-2 family.
In earlier work we found that expression of the pro-survival protein MCL-1 was required for the continued growth of MYC-driven lymphomas. We have been working with the pharmaceutical company Servier to test novel BH3 mimetic drugs targeting MCL-1 for cancer therapy and related drugs entered clinical trials in 2018.
We are currently seeking to identify factors that could confer resistance, either primary or acquired, to these MCL-1 targeting drugs with the aim to find strategies that could overcome resistance.
Project resources
- Survival protein a potential new target for many cancers
- New compound shows promise in treating multiple human cancers
Team members: Dr Sarah Diepstraten and Ms Catherine Chang
Investigating mutant p53 in cancer
Approximately 50 per cent of human cancers harbor mutations in the tumour suppressor p53 that result in reduced sensitivity to many conventional chemotherapeutics and a poor prognosis for the patients. We seek to understand how exactly these mutations in p53 contribute to the growth of cancer cells, in particular we are interested to know if there are neomorphic gain-of-function effects of mutant p53. Additionally, we aim to determine if mutant p53 contributes to the growth of established tumours, thereby identifying it as a therapeutic target. For these experiments we have generated novel and sophisticated pre-clinical models of mutant p53 cancers.
Project resources
Team members: Ms Elizabeth Lieschke and Dr Zilu Wang, PhD students co-supervised by Dr Gemma Kelly and Professor Andreas Strasser
Investigating the role of the Epstein-Barr virus in lymphomas
Approximately 200,000 cancers annually are associated with the Epstein-Barr virus (EBV). We are researching the role of EBV in two types of lymphoma – Burkitt’s lymphoma (an aggressive B cell lymphoma), and T/NK cell lymphoma.
In a subset of Burkitt’s lymphomas, EBV expresses a viral homologue of the cellular pro-survival BCL-2 proteins, called BHRF1. We seek to understand how BHRF1 interacts with the cellular apoptotic machinery to block cancer cell death. In the setting of EBV-associated T/NK cell lymphomas we aim to understand how viral proteins contribute to tumour growth and to find alternative therapeutic options since these patients currently have a very poor prognosis.
Team members: Mr Nenad Sejic and Ms Catherine Chang and also a collaboration with the group of Dr Claire Shannon-Lowe at The University of Birmingham
Is there therapeutic potential in targeting the BCL-2 pro-survival proteins BCL-W and BFL-1/A1 for cancer therapy?
BH3 mimetic drugs targeting the pro-survival protein BCL-2 have shown efficacy in the clinic for the treatment of patients with chronic lymphocytic leukemia (CLL).
More recently, BH3 mimetics targeting the related BCL-2 family protein, MCL-1, have shown promise for the treatment of certain blood cancers in pre-clinical models and entered clinical trials for these cancers in 2018.
Two of the other BCL-2 pro-survival proteins, BCL-W and BFL-1/A1, are by comparison relatively understudied. We are using genetically engineered pre-clinical lymphoma models and CRISPR/Cas9 genome editing of blood cancer cells to determine if drugs targeting BCL-W and BFL-1/A1 would have therapeutic potential.
Team members: Dr Sarah Diepstraten, working in collaboration with the groups of Professor Andreas Strasser and Associate Professor Marco Herold