Our group works on the development of engineered T cells for the treatment of children’s solid cancers. A major focus has been the identification anti-cancer drugs that can be repurposed using synthetic biology to fine tune CAR-T function through regulation of expression at the protein level. This approach has been instrumental in the recent award of CRUK/NCI Cancer Grand Challenge for which the primary supervisor is the CAR-T lead, and has led to the award of two large academic clinical trials grants for phase I testing of the technology. The project will build on discoveries emerging from existing grant awards for further fine-tuning of CAR-T function on paediatric solid cancer models. The experimental approaches will be focussed on primary T cell culture, viral transduction, molecular biology and genetic animal models.
Potential secondary supervisor: James Arnold, KCL Comprehensive Cancer Centre
Are you interested? Contact John by email.
Metastatic prostate cancer responds to hormone therapy but outcomes vary, with 20% of patients succumbing to their disease within 18 months and 20% in remission at 8 years. My group researches treatment resistance and consequently the biological underpinnings of this highly-variable disease course. To achieve this, we have assembled data-sets of tumour biopsies (N=4800) and plasma DNA (N=2000) from patients participating in diagnostic or therapeutic clinical trials (https://www.stampedetrial.org, https://www.ctc.ucl.ac.uk/TrialDetails.aspx?Trial=165, https://www.reimagine-pca.org, https://ncita.org.uk/climate-study/). In collaboration with Professors Jamal-Hanjani (UCL) and Swanton (Crick), a sub-set of patients have had extensive sampling post-mortem of lethal metastases in the PEACE study (https://www.ctc.ucl.ac.uk/TrialDetails.aspx?Trial=134). We have implemented novel approaches for extracting high-quality molecular data from clinical samples, including bespoke interrogation of genomic lesions (Orlando, NAR Cancer, 2023) and methylation/epigenetic structures (Wu, JCI, 2020) and expression profiling (Grist/Parry, 2024). By integrating with prospectively-collected, high-quality clinical data, we identify clinically-relevant biological pathways that we then target with biomarker-stratified approaches.
Are you interested? Contact Gert Attard by email.
Our research group focuses on investigating mechanisms of resistance to chimeric antigen receptor T (CAR-T) cells in B-cell malignancies and developing strategies to overcome resistance through CAR-T cell engineering, optimising CAR-T manufacturing processes and the use of allogeneic CAR-T cells. We use single cell OMICS techniques to interrogate biobanked primary samples from lymphoma and myeloma patients treated with commercial anti-CD19 and anti-BCMA CARs through our UK and Dresden University collaborations, and identify gene expression profiles that correlate with response/resistance to CAR-T cells. CRISPR/Cas9 and base editor nucleases are used to disrupt implicated resistant pathways in T cells to enhance persistence and anti-tumour activity for both autologous and allogeneic CAR-T cells. We operate a GMP CAR-T manufacturing facility that enables improvements in manufacturing processes to be evaluated in early phase clinical studies such as the CRUK funded pCAR19 study for refractory B-cell lymphomas due to open at KCH in 2025.
Potential secondary supervisor: Waseem Qasim, UCL Institute for Child Health, or Jeff Davies, QMUL Barts Cancer Institute
Are you interested? Contact Reuben by email.
My group performs cutting edge research into neuroimaging and artificial intelligence. A core theme has been using natural language processing to label large clinical brain MRI datasets (>100,000s scans), then applying computer vision algorithms to distinguish normal and abnormal, to build an accurate triage tool. We then can apply this model to brain tumour tasks where there is less data. One such task could be developing immunotherapy biomarkers. I collaborate with groups nationally and internationally (e.g., GLiMR, RESPOND, EORTC, RANO) leveraging opportunities for further external validation as well as federated learning. Our research questions are ambitious but grounded and informed by neuro-oncology stakeholders. The research questions are further developed through position statements (which I lead on or co-author), including on the utility of interval imaging in standard of care brain tumour management, and on early diagnosis of brain tumours.
Are you interested? Contact Thomas by email.
The prognosis for cholangiocarcinoma (CCA) or bile duct cancer is poor and the incidence is rising. The SAFIR-ABC 10 study is an international 800-patient randomised phase 3 study investigating the role of sequential targeted therapy in advanced CCA. Of these, between 5 to 10% of the patients will have pre-existing primary sclerosing cholangitis (PSC), a risk factor for CCA. The biology of PSC is poorly understood, and we are currently investigating inflammatory and immune signatures linked to CCA resistance as well as prognostic and early detection biomarkers. We have used Olink proteomics in blood and Spatial Biology (GeoMx, CosMx) in tissue (whole transcriptome and proteome) as well as sequencing immune cells directly from patients. As such, SAFIR-ABC10 will provide an ideal platform on which to examine the subgroup of approximately 50 patients with PSC driven CCA in the context of prospectively documented genomic and clinical trial level data.
Immunotherapy offers hope for patients with advanced metastatic cancers but only a subset of patients show enduring responses. The YAP/TAZ mechanotransduction pathway has emerged as a key mediator of immunotherapy resistance. YAP/TAZ activation is also critical for the activation of cancer-associated fibroblasts (CAFs), which can also suppress anti-tumour immunity. Pharmacological targets within the YAP/TAZ pathway remain poorly defined. Using a multidisciplinary approach, we have identified novel Rho-regulated kinases as activators of the YAP/TAZ pathway. Genetic mouse model data suggests targeting these kinases can promote anti-tumour immunity. Further, we have developed selective inhibitors (QMI/Dundee) to target these kinases, which potently suppress YAP/TAZ output. We will assess inhibitor efficacy in solid cancer models focussing on: (i) impact on anti-tumour immunity, checkpoint response and immune landscape; (ii) mechanistic impact on mechanotransduction signalling in CAFs and cancer-cells in vivo; (iii) Immune-competent human tissue explant models to validate immune regulatory drugs. Pre- and post-treatment tissues will be analysed using multiplexed flow cytometry, immunofluorescence and spatial transcriptomics using existing pipelines.
Potential secondary supervisor: Mark Linch, UCL Cancer Institute
Are you interested? Contact Angus by email.
This project aims to study the mechanisms of response and resistance to immunotherapy in ex vivo systems such as tumour fragments established from human colorectal cancer (CRC) patients that preserve the properties of both tumour and associated tumour microenvironment (TME).
We recently showed that (1) cytotoxic lymphocytes and antigen-presenting macrophages are key for response of CRC patients to immunotherapy, (2) the local TME niche impacts on the functionality of tumour cells and (3) tumour immunophenotypes can stratify patients for treatment. Here we propose to investigate the mechanisms of tumour-TME functional interactions and how these impact on immunotherapy outcome.
This project is best suited for a clinical scientist because it sits at the intersection of cancer genomics and immunology, human tissue biology, and clinical research. The student will set up the ex vivo platform from fresh tumours and investigate the effect of perturbation by immunotherapies on both tumour and TME.
Potential collaborators: Manuel Rodrigues-Justo, UCL Cancer Institute, Jennifer Hay, Crick
Are you interested? Contact Francesca by email.
Our research aims to understand the epigenetic regulation of transposable elements (TEs) and their role in cancer development. Epigenetic dysregulations in cancer provides a fertile ground for their activation. We focus on how dysregulated TEs act as gene regulators, triggers of anti-tumor immunity and drivers of cancer progression, seeking to harness these elements for innovative cancer treatments. Using advanced single-cell, bulk-level epigenomics and transcriptomics with functional assays and drug screens, we aim to comprehensively delineate the molecular and cellular functions of TEs in cancer genomes.
Using cell line models and primary patient samples, our research areas include:
- Determining cis-regulatory roles of TEs in cancer.
- Investigating TE-mediated immune responses in cancer.
- Exploring the role of TEs in cancer evolution from pre-cancerous stages to relapse.
This research offers clinician scientists a unique opportunity to explore the interplay between epigenetics and oncology, contributing to the development of novel therapeutic strategies.
Are you interested? Contact Özgen by email.
My laboratory focusses on investigating the biological phenotype of tumour cells capable of metastatic spread to the leptomeninges, a unique type of metastatic spread which is devoid of effective treatment strategies. Patient derived models developed from cerebrospinal fluid samples are used to unpick cell biophysical properties and tumour microenvironment interactions within the leptomeningeal niche, including interplay with host meningeal cells and astrocytes. Uncovering key dependencies of these metastatic cells will help elucidate novel treatment targets. Further, through establishing a multi-centre cohort of primary tumour material from patients who develop leptomeningeal metastasis, we are developing predictive algorithms to define a high-risk patient group through digital pathology analysis. In parallel, we are developing clinic-ready cerebrospinal fluid liquid biopsy methods for the improved detection of leptomeningeal metastatic spread.
Potential collaborators: Leanne Li, Crick, Victoria Sanz-Moreno, ICR
Are you interested? Contact Amanda by email.
Antibody drug conjugates (ADCs) are revolutionising the treatment of several cancers and are among the most promising new therapeutics for gastro-oesophageal adenocarcinomas (GOA). Key factors underlying suboptimal treatment response for ADCs are cancer cell plasticity and evolution which confer intratumour heterogeneity of target-antigen expression. The ability of cancer cells to access distinct differentiation or embryonal states is a likely explanation for this antigen expression plasticity, as shown by us for a CRC specific target. The project will focus on CLDN18.2 ADCs which are in development for GOAs.
Potential secondary supervisor: Marnix Jansen, UCL Cancer Institute
Are you interested? Contact Marco by email.
I have a research background in the translation of novel chimeric antigen receptor (CAR) T cell therapies into phase 1 studies and reverse ‘bed to bench-side’ research. My research has revolved around understanding the mechanisms of response, resistance, and toxicity from CAR T cell therapy, with the aim of designing better therapies for patients. Recently I have been investigating the mechanisms of prolonged cytopenia following CAR T cell therapy, through in vitro assays and in vivo humanised mouse models. Additionally, I have been undertaking studies to explore the mechanisms leading to movement and neuro-cognitive toxicity following BCMA targeting CAR T cell therapies for multiple myeloma. My laboratory will be conducting translational studies utilizing primary patient samples and designing new CAR T cell therapies with a focus on reducing toxicity and improving efficacy.
Are you interested? Contact Charlotte by email.
My group focuses on understanding cancer resistance and normal tissue toxicities to radiation and drug combinations with a focus of gastrointestinal GI malignancies.
We have developing 3D models of gastro-intestinal cancers (precision cut tumour/tissue slices) to study early radiation (Xray and protons) effects on tumour/immune /microenvironment and inform how to construct improved radiation-drug combinations. We are also using artificial intelligence models that use imaging, radiation dose, clinical and pathology data to develop prediction models. These might help us identify how to better tailor radiation treatments. I developed and lead clinical trials, using novel radiotherapy including protons in GI cancers (oesophagus pancreas, hepatobiliary) and we would use trial and clinically available data to develop these models.
My team includes clinicians and scientists and I have supervised >15 students (clinicians, physicists and biologists). The project will involve developing biology, physics and computational skills that will inform next radiation clinical trials.
Are you interested? Contact Maria by email.
This research project aims to evaluate the use of circulating tumour DNA (ctDNA) as a biomarker to predict clinical benefit from concurrent chemoradiotherapy (cCRT) in locally advanced unresectable non-small cell lung cancer (NSCLC). We will analyse plasma samples from existing cohorts, the RadNet City of London biobank and TRACERxEVO study, to assess ctDNA dynamics before and after cCRT. The project will compare the efficacy of tumour-informed and tumour-naive ctDNA panels with a mutation and methylation-based approach respectively. Statistical analysis will determine if differences in ctDNA characteristics correlate with patient outcomes to select the optimum platform for clinical trials in this setting. This is clinically important given the role of consolidation immunotherapy following cCRT, where some patients do not need consolidation immunotherapy (e.g. 12 months of Durvalumab) and some may benefit from escalation of consolidation and peri-radiotherapy immunotherapy treatments which are currently in clinical trials.
Are you interested? Contact Crispin by email.
This project tackles a critical challenge in lung cancer: developing strategies for early intervention. Our research focuses on extrachromosomal DNA (ecDNA), abnormal circular DNA structures that amplify oncogenes, thereby accelerating tumour growth and metastasis. We’ve identified ecDNA in pre-invasive lung lesions, suggesting its potential role in cancer initiation. EcDNA is particularly problematic because it harbours amplified oncogenes, resulting in uncontrolled cell proliferation and resistance to therapy. By understanding how ecDNA forms and targeting the DNA repair pathways involved (e.g., NHEJ), we aim to develop novel therapeutic strategies to prevent ecDNA formation and improve patient outcomes. This research has the potential to transform early lung cancer intervention and treatment.
Potential secondary supervisor: Nitzan Rosenfeld, QMUL Barts Cancer Institute
Are you interested? Contact Sam by email.
We aim to understand the mechanisms of the receptor tyrosine kinase c-MET (or MET) in promoting cancer metastasis. c-MET is overexpressed or mutated in many tumours and, through affecting cell adhesion, migration, invasion, survival and angiogenesis, is as a major target for cancer therapy. We study the signalling of c-MET in relation to its endosomal trafficking (how it is moved around the cell in vesicles) and the effects on tumour cell migration and invasion in vitro and in vivo. We use confocal microscopy, live imaging, biochemistry, proximity proteomics, bioinformatics, trafficking / internalisation assays, co-culture spheroid invasion assays, and in vivo tumorigenesis assays. We investigate the clinical relevance of our findings on patient samples through collaboration with clinicians. We work on breast, pancreatic, lung, bladder, ovarian cancer and glioma. A better understanding of the molecular biology of c-MET signalling will lead to improved cancer treatment and thus patient outcome.
Are you interested? Contact Stephanie by email.
I am a surgeon-scientist combining clinical research with laboratory investigations. My clinical research interests include tissue banking, clinical trials, innovative surgical techniques, epidemiology, meta-analysis and patient care pathways. My translational/laboratory research interests include pancreatic cancer stroma and tumour-stroma cross-talk including cell signalling, adhesion, metastasis, invasion leading to innovative therapies and novel biomarkers. I have supervised 35 MD / PhD students with 20 of them being clinical research fellows. Many of the clinical research fellows are in academic leaders globally or have founded commercial start-up companies. I have trained surgeons, oncologist and pathologist and mentored gastroenterologists. I believe in inter-disciplinary research as evidenced by publication track record with co-authorship across many areas and clinical trials emanating from laboratory research particularly in stromal biology of pancreatic cancer. Recently we have started investigating duodenal cancer (largest cohort globally), melanoma liver metastasis and colorectal liver metastasis due unique access to patient samples.
Are you interested? Contact Hermant by email.
A significant number of breast cancer patients develop brain metastasis (BM) or distant metastases, despite previous local and systemic treatments. For patients with oligometastasis, surgical excision or high dose radiotherapy such as radiosurgery (SRS) or stereotactic body radiotherapy (SBRT) to the metastases may help to achieve long-term local control. Following local treatments, patients will usually undergo further systemic treatments according to the breast cancer subtypes and previous treatments.
Patient-derived organoids (PDOs) have been shown to recapitulate patients’ tumours and could help to identify effective therapeutic regimens (1). We have been generating PDOs from primary breast cancer tissues. We will be starting SOTO-BC study (lead PI: Dr. Kong), a prospective observation study to correlate the treatment Sensitivity of PDOs with Treatment Outcomes in breast cancer patients with brain or extra-cranial metastases. SOTO-BC study aims to generate PDOs from resected or biopsied brain and/or extra-cranial metastasis and assess the potential of these PDOs in predicting treatment outcome in patients.
The specific aims of a potential PhD
Aim 1: To generate PDOs in SOTO-BC study and correlate the treatment sensitivity with patients’ outcomes
Aim 2: Assess genetic evolution and heterogeneity of primary tumours
Aim 3: Characterise the impact of identified driver mutations on tumour microenvironment phenotypes
Aim 4: Validate optimum treatment (including immunotherapy) in PDOs
Potential collaborators: Teresa Marafioti, UCL Pathology, Heba Sailem, KCL Comprehensive Cancer Centre, Jamie Dean, UCL Medical Physics & Biomedical Engineering
Are you interested? Contact Anthony by email.
Myeloproliferative neoplasms (MPNs) pose significant clinical challenges: thrombosis, bone marrow fibrosis, and progression to acute myeloid leukaemia (AML). Current treatments are largely non-curative, immunomodulatory treatments like JAK inhibitors, interferon-alpha, and Bromo- and Extra-Terminal domain (BET) inhibitors show promise but have a 20 to 50% non-response rate. No well-defined immunological biomarkers exist to predict the suitability of these treatments.
This project aims to address these gaps by developing a comprehensive data model integrating immunome, clinical, and genomic findings. We will generate a scoring system for patient stratification to inform treatment decisions, predict progression, and anticipate responses to immunomodulation. Key components include:
- Identifying immune profiles in bone marrow (BM) and predicting responses to immunomodulation using advanced imaging and analytical techniques.
- Optimising a high-definition imaging technique for BM to define spatial cellular communities specific to MPN subtypes and improve immune profile recognition.
The clinical research fellow will learn a variety of cutting-edge technologies in this project, such as imaging mass cytometry, single-cell RNA sequencing, and computational approaches for data analysis and integration.
Are you interested? Contact Shahram by email.
High-grade serous ovarian cancer (HGSOC) is a leading cause of cancer patient death. Platinum-based chemotherapy and PARP inhibitor maintenance is initially effective but 80% patients will relapse and eventually die with chemotherapy-resistant, untreatable cancer. Cancer treatments are selective pressures that drive adaption within cancer. We have already demonstrated that drug dosing regimens that respond to these evolutionary dynamics prolong drug sensitivity and achieve long-term tumour control. This is known as Adaptive Therapy (AT) and we are currently testing this approach in 10 UK hospitals via the ACTOv clinical trial (Adaptive ChemoTherapy in Ovarian cancer: NCT05080556). This work was spearheaded by our previous CRUK clinical fellow.
Potential PhD projects would align with workstreams in the lab aimed at understanding the mechanisms that underpin AT. These include interrogation of genetic and non-genetic mechanisms and characterisation of evolution within the tumour microenvironment with potential to reveal novel immunotherapeutic targets. Our vision is that this new knowledge will facilitate development of clinical trials in which therapies are directed by the evolution of resistance in individual patients over time.
Are you interested? Contact Michelle by email.
My group focusses on chimeric antigen receptor (CAR)-T cells, which are a transformative new type of cellular immunotherapy. We are part of the UCL CAR-T programme which is one of the largest and most successful in the world, with capabilities across the spectrum from preclinical discovery to clinical trial delivery. Multiple projects developed in my lab have gone on to be tested in clinical first-in-human studies. We currently have projects in development of ‘off the shelf’ allogeneic CAR-T, CAR-T for T cell cancers, novel engineering approaches to enhance CAR-T efficacy and persistence, CAR-T for solid tumours (currently ovarian, lung cancer) and are also happy to develop a new proposal based upon a candidate’s specific disease interest. Our projects are wet-lab based and include both in vitro and in vivo (mice) work. A project would suit a haematology or oncology trainee with a strong interest in cellular therapy and translational research – the aim of all projects in the lab is to translate to clinical testing.
Are you interested? Contact Paul by email.
Prof Manchanda’s research interests are focused on Targeted Precision Prevention. This includes population-based genetic testing, mainstreaming genetic testing and precision medicine approaches for risk prediction, stratification, risk management, targeted ovarian cancer screening and targeted cancer prevention, along with health economic issues related to these areas of research. He is the PI for PROTECTOR, PROTECT-C, DETECT-2, OVACATCH, PRESCORES, SECRETS, JHCR, UKCOGS, SIGNPOST studies.
Prof Menon has strong research interests in ovarian cancer symptoms and earlier diagnosis, ovarian cancer screening, biomarker research, prevention, and management of high-risk women. She has led multiple studies/trials in these areas, including UKCTOCS (general population ovarian cancer RCT). She is PI for the UKCTOCS, UKFOCSS and UKOPS biobanks.
The research fellow, has the opportunity to work across these areas with a particular focus on symptoms and early diagnosis, as well as screening for ovarian cancer. The team has access to unique cohorts/bioresource of patients with early disease.
Potential co-supervisor: Usha Menon, UCL MRC Clinical Trials Unit
Are you interested? Contact Ranjit by email.
Attempts to develop specific immunotherapies for acute myeloid leukaemia (AML) have been challenging due to difficulties in identifying AML-specific cell surface antigens that are not present on normal HSCs. We hypothesise that neoepitopes produced by dysregulated RNA splicing offer a unique immunotherapeutic opportunity for AML patients harbouring mutations in the splicing machinery. The SRSF2 P95H mutation is particularly prevalent in older patients with high-risk AML.
In this research project, the candidate will use CRISPR/Cas9 to generate isogenic SRSF2 mutant AML cell lines and analyse patient samples to discover neoepitopes specific to SRSF2-mutated AML. The candidate will gain experience in RNA-seq, bioinformatics and mass spectrometry to identify neoepitopes presented on different MHC complexes in AML cells. T-cell immune responses against different peptide libraries will be identified using our recently developed in-house reporter system (patent pending). We ultimately aim to develop novel immunotherapies targeting neoepitopes specific to splicing factor mutated AML.
Potential secondary supervisor: Kevin Rouault-Pierre, QMUL Barts Cancer Institute
Are you interested? Contact Marc by email.
Metastasis remains the principal cause of death due to cancer and we need better tools to prevent established metastases from becoming lethal. Pancreatic ductal adenocarcinoma (PDAC) has a <5% five-year survival, metastasising to the liver, lung and peritoneum. These three sites are very different from the original pancreas, so the metastases must develop organ-specific responses to ensure their survival, growth and spread. These organ-specific changes allowing metastases to develop are largely unknown. We have generated novel mouse PDAC models where de novo expression of integrin αvβ6 (as occurs in humans) promotes metastasis to liver, lungs and peritoneum. Using laser capture microscopy of PDAC metastases from these three organs, together with spatial transcriptomics, spatial proteomics and multiplex immunofluorescence, we will examine the changes in gene, protein and cellular infiltrate in metastases (cancer cells and adjacent metastasis microenvironment [MME] analysed separately) from the different organ sites, comparing with the relevant normal tissue and original tumour. We expect to identify genes and matrix proteins selectively regulated in the metastases or their MME of the different organs that will inform development of metastasis-targeting therapeutics. Training in the multiple different research skills described will be complemented with bioinformatics and image-analysis training so the CRTF can take ownership of the analysis of the data they generate and prepare them for designing their own research programme in the future.
Potential secondary supervisor: Ilaria Malanchi, Crick
Are you interested? Contact John by email.
Gastro-oesophageal cancer carries a poor prognosis due to its resistance to chemotherapy and the presence of early micrometastatic disease. Models based on clinical variables and visual assessment of standard-of-care scans alone are not sufficient to predict the presence of residual or early recurrent disease. The output of this proposed programme will be a combined tissue (immune imaging)-imaging (MR)-blood (immunogenomic)-patient derived organoid (PDO) test at baseline. This baseline test will separate the high from low-risk patients and the ‘equivalent’ blood tests will be deployed for longitudinal monitoring to trigger additional imaging tests to confirm/locate the recurrences and guide future therapies.
For data integration we have established a Bayesian-based machine learning (ML) approach, currently being applied on the H&N Early Recurrence Detection of (HERD) study, a CRUK programme grant (£2.82M) supported study between KCL, UCL and associated Trusts (GSTT, KCH, UCLH) and QMUL. Specifically, we will use imaging-multiomics and multiparametric molecular analyses to interrogate treatment response on patient-derived-organoids (PDOs) to identify new individualised immune-based targets for treating recurrence.
Potential secondary supervisor: Martin Foster, UCL Cancer Institute
Are you interested? Contact Tony by email.
Malignancy associated haemophagocytic lymphohistiocytosis (mHLH), is a rare but often fatal hyperinflammatory syndrome associated with cytokine storm, proliferation of activated macrophages and haemophagocytosis associated with an incidence of 1% in haematological cancers and up to 10% of patients with acute myeloid leukaemia. Patients develop multiorgan failure resulting with a mortality of up to 70%, in part due our limited understanding of the disease process and a lack of effective therapeutic options.
The hypothesis underlying this study is that the strong association of mHLH with haematological cancers derives from crosstalk between malignant haematopoietic cells, and tumour associated immune cells, leading to HLH initiation and propagation. We will undertake spatial transcriptomics and proteomics and single cell RNAseq on matched human samples with and without mHLH as a discovery tool to understand its evolution and define novel treatment avenues.
Dr Paynes lab studies myeloid disorders and clonal haematopoiesis. Dr Payne lab also runs the UCL/UCLH biobank for health and disease/haematology project, which has led to the initiation of a collection of samples of patients with haematological malignancy associated haemophagocytic lymphohistiocytosis (HLH). She is part of a national MRC funded rare disease consortia ‘UK HistioNode’ which brings together clinicians and researchers studying histiocytic disorders (including HLH) across the UK and extends the sample collection initiated at UCLH to encompass additional UK sites.
Are you interested? Contact Elspeth by email.
A hallmark of cancer is replicative immortality. In ~10% of cancers, this is achieved through the alternative lengthening telomeres pathway (ALT). A proportion of ALT tumours is driven by ATRX or DAXX mutations. We have shown that up to 60% of undifferentiated pleomorphic sarcomas demonstrate ALT and there are other sarcomas like osteosarcoma which also harbour high ALT levels. New therapeutic vulnerabilities to ALT are available necessitating further pre-clinical research to identify appropriate biomarkers, a characterisation of ALT across other sarcoma types and the generation of cell models with the aim of developing a clinical trial. This project involves:
- Investigating the heterogeneity of ALT using whole genome sequencing data and C-circle assays and associate this with clinical data.
- Development and functional characterisation of in vitro models of ALT using patient derived cell lines.
- Evaluating differences between ALT positive tumours driven by ATRX vs mutations in other genes.
Potential secondary supervisor: Simon Boulton, Crick
Are you interested? Contact Nischalan by email.
This project will suit either a medical oncologist with an interest in imaging or a radiology fellow. The studies available for consideration involve the use of Luminal Water Fraction (LWF) imaging and VERDICT MRI. in the diagnostic (CLIMATE – NCT05020522) or screening (LIMIT – ISRCTN45191339) setting LWF and VERDICT will be tested; and for lesion characterisation using Hyperpoalrised MRI (Validate pro – NCT05017181). This work will focus on the development and clinical translation of these new MRI techniques. These technologies are targeted to provide early detection and characterisation of prostate lesions to determine decision to biopsy and decision to treat.
Are you interested? Contact Shonit by email.
Lung and pancreatic cancer are tumour types of urgent unmet clinical need associated with late-stage presentation and consequent dismal prognosis. Cancer interception is an emerging paradigm with transformative clinical potential that aims to block the progression of preinvasive lesions to invasive disease. However, the underlying biology which determines carcinogenesis remains poorly defined. We and others have identified dysfunctional and regulatory neoantigen specific T cells which appear to foster immune regulation during carcinogenesis.
Here the candidate will use an extensive collection of preinvasive and early-stage clinical samples and apply immune multi-omics and functional analysis to identify actionable inhibitory pathways which may enable multi-cancer interception. Targets will then be studied alone or in combination with pioneering, neoantigen vaccines in the prototype or clinical development phase. The fellow will join a vibrant group of immunologists, bioinformaticians and clinicians in the Reading and Tree labs using a suite of cutting-edge wet lab antigen-specific profiling, 3D explant and computational tools to gain world-leading insight and skills in a future pillar of clinical oncology.
Potential secondary supervisor: Timothy Tree, KCL Peter Gorer Department of Immunobiology
Are you interested? Contact James by email.
Non-small cell lung cancer is a devastating disease with a high propensity to metastasise. Interestingly, not all metastases behave the same, with some responding to therapy while others in the same patient progress. In addition, ongoing genomic analysis indicates that some metastases seed others, while others appear to be ‘dead ends’. This project will investigate how the microenvironment determines the differences in the behaviour of metastases. Carefully annotated samples from the TRACERx and PEACE studies collected longitudinally, including post-mortem, will be analysed using state of the art spatial proteomic methods and novel analytical tools to define features that correlate with therapy response, in particular immunotherapy response, and whether metastases are can seed other metastases or are dead-ends. Goals include understanding the biology of metastases, determining the spatial features of therapy resistant and seeding metastases – with a focus on the extracellular matrix and structural environment, and identifying actionable targets.
Potential secondary supervisor: Mariam Jamal-Hanjani, UCL Cancer Institute
Are you interested? Contact Eric by email.
My research group focuses on identification of biomarkers of ductal carcinoma in situ and lobular breast cancer progression through genomic analysis of tumour tissue and the tumour microenvironment. Invasive lobular carcinoma’s (ILCs) account for 10-15% of invasive breast cancers and are increasing in incidence. They can recur more than 10 years after diagnosis and there is evidence suggesting that ILCs are unique at the molecular level and differ in their repertoire of driver genes and micro-environmental composition compared to the more common ductal breast cancers. Our research aims to understand the molecular evolution of ILCs by isolating circulating tumour cells and circulating tumour DNA from serial blood tests from women with different stages of ILC and performing in depth genomic analyses. We are particularly interested in understanding how often the clones that become metastatic are already present in the primary cancer at diagnosis and how many are due to treatment related evolutionary pressures.
Potential secondary supervisor: Eric Sahai, Crick
Are you interested? Contact Elinor by email.
We use targeted protein degradation to study cancer biology, evolution, and develop new therapies, e.g. molecular glues and PROTACs (proteolysis targeting chimeras), that degrade proteins critical for cancer cell survival. Targets may within tumour cells or within the microenvironment. In contrast, we also investigate fusion driven cancers where, by inhibiting an E3 ligase and blocking degradation, we cause increased expression of the fusion oncoprotein to a critical level leading to cancer cell death. Through these approaches we develop highly selective and effective therapies for diverse cancers including AML and sarcoma.
To identify, study, and exploit targets for enhancing or inhibiting degradation, we employ a broad range of techniques in cellular, molecular, and chemical biology including fluorescent based reporters, CRISPR Cas9 editing and screens, organoid models of disease, and DNA encoded library drug screens. Our work is highly collaborative with contributors from AI/machine learning, medicinal chemistry, structural biology, and protein biology.
Potential secondary supervisor: Paolo Gallipoli, QMUL Barts Cancer Institute
Are you interested? Contact Rob by email.
Translating kinase biology to new therapies: Kinases remain important drug targets, research in the Soliman lab seeks to understand the biological response to kinase rewiring/signalling in cancer to predict patient responses and enable more sophisticated approaches to target pathological kinase signalling. We are particularly focussed on a pathway we have termed the mitotic failsafe pathway, which exposes a tumour specific vulnerability as it is found to be conditionally required in TP53 mutant cancers. Targeting vulnerabilities acquired by cancer cells (and thereby avoiding normal, non-cancerous tissue) is a promising anti-cancer strategy, the use of PARP inhibitors in HRD tumours, is an example of one such approach. Our data suggests that a subset of tumours (e.g. non-small cell lung carcinoma, high grade serous ovarian cancer) have a defective G2 decatenation checkpoint; cells enter mitosis before adequately detangling (decatenating) replicated chromosomes which can lead to segregation errors and genomic instability. We demonstrated cells with a defective G2 catenation checkpoint are reliant on signalling through the mitotic failsafe pathway and inhibition of key pathway players drives mitotic catastrophe and apoptosis. Our evidence suggests p53 pathway regulation loss, coupled with a defective G2 decatenation checkpoint presents an opportunity to develop novel targets for this cancer-specific vulnerability.
Are you interested? Contact Tanya by email.
Neuroblastoma is a childhood cancer of unmet need, with only half those with high-risk disease surviving. Molecular radiotherapy – the systemic administration of biologically targeted radiopharmaceuticals – is an attractive therapeutic option given the widespread nature of disseminated disease, its intrinsic radiosensitivity, and a range of molecular targets which can be exploited by different biomolecules carrying different radionuclides. We have an established bench to bedside research programme ranging from innovative radiochemistry to produce novel radiobiotherapeutics, their preclinical evaluation, and a portfolio of groundbreaking international early-phase clinical trials to test new agents and combinations. This project comprises a mix of laboratory research to develop and evaluate new radiopharmaceutical therapies, and test how their efficacy may be enhanced by the use of high linear energy transfer alpha emitting radionuclides, by the use of novel radiation sensitisers, and combinations with immunotherapy. In parallel, there will be clinical trial development work, with a focus on radiation dosimetry and immunotherapy combinations.
Potential collaborators: Mark Gaze, UCL Cancer Institute, Graeme Hewitt, KCL Comprehensive Cancer Centre
Are you interested? Contact Jane by email.