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.

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.

Are you interested? Contact John or Pilar by email.

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.

Emerging evidence suggests factors other than smoking contribute to lung cancer, with an increasing proportion of never-smoker lung cancers diagnosed. My laboratory will focus on understanding how the immune response to viral infection contributes to lung cancer. One family of enzymes involved in the antiviral immune response are APOBEC3 enzymes. Unfortunately, an off-target effect of APOBEC3 activity is damage to the host genome. Interestingly, in certain populations APOBEC3 genes are mutated in the germline. These APOBEC3 germline mutations stabilize and activate the enzyme and so could be a contributing factor to the increased risk of lung cancer observed in East Asian, Native American, and Oceanic populations (prevalence 37 – 93%). The precise mechanisms by which APOBEC3 genes drive lung cancer are unknown. Linking preclinical models to samples derived from lung cancer patients in large cohort studies, my lab will delineate these mechanisms and define new ways to prevent lung cancer.

Are you interested? Contact Deborah by email.

Detection of patients at risk of developing HGSC or at pre-cancerous stage which are amenable to  prevention is crucial to impact disease mortality. Our team has produced strong preliminary data regarding tumour initiation in the fallopian tubes and is now exploring interactions between epithelial and immune cells to develop biomarkers of early detection and disease prevention. We lead the NEMO (Novel Markers of Ovarian Cancer) Consortium/programme which has been funded by CRUK/ACED and incorporates other UK and US centres. Our multidisciplinary team of clinicians and scientists have an active programme with recruitment of cancer, high-risk genetic and healthy patients with collection of human samples (through the DARWIN study) and use a combination of 3D primary organoid models, co-cultures and cutting-edge single cell approaches to understand tumour-initiating events. The candidate will develop skills in basic and translational research which will set a strong foundation for any future independent research programme.

Are you interested? Contact Filipe 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.

We have been studying metabolism in B cell lymphomas and have uncovered several metabolic perturbations that promote rapid apoptosis of lymphoma cells, but do not do so in normal stromal and epithelial cells. We now need to translate our findings to in vivo lymphoma models and to assess how our perturbations affect the metabolism and viability of the lymphoma cells and what role the tissue microenvironment plays in these responses. We also hope to generate novel drugs based upon specific targeting of existing metabolic drugs to the mitochondria.

We will use multiple complementary analytical techniques, including cutting-edge metabolite and lipid mass spectrometry, single-cell proteomics and state of the art imaging techniques. Through this project we aim to validate novel combinations of drugs that may inform future clinical practice in lymphoma.

Potential secondary supervisor: Ingo Ringshausen, UCL

Are you interested? Contact Andrew 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.

Despite the recent introduction of several targeted therapies, many acute myeloid leukaemia (AML) patients have short-lived responses to treatment, eventually succumbing to relapsed disease. Resistant clones often demonstrate metabolic plasticity to withstand therapeutic pressure and drive disease recurrence. Our lab focusses on the role of specific metabolic adaptations in supporting AML cells survival and evolution following therapy. Recently, we highlighted the role of fatty acid (FA) metabolism which is often co-opted by AML cells to withstand therapeutic pressure or metabolic stress encountered in the microenvironment. This, in turn, creates specific dependencies which can be therapeutically actioned. This PhD Project will investigate the cell intrinsic plasticity of FA metabolism in AML therapy-resistant cells, its modulation by microenvironmental cues and how this is leveraged by AML cells to drive therapy resistance. The final aim is to design biologically sound and effective therapies targeting FA metabolism dependencies and to prevent disease recurrence.

Are you interested? Contact Paulo 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. Our group is undertaking studies to explore the mechanisms of neuropsychiatry complications of CAR T cell therapy, we are also actively translating two novel CAR T constructs to early phase clinical trials for haematological malignancies.

Are you interested? Contact Charlotte by email.

Paediatric high-grade gliomas (pHGG) are the leading cause of cancer-related death in children and remain without effective therapies. Insights from cancer neuroscience reveal that pHGG integrate structurally and functionally with the neural circuits they invade such that neural activity robustly promotes tumour growth. However, most of this evidence stems from preclinical models which do not fully recapitulate human-specific neurobiology or therapeutic relevance. Our group has recently leveraged computational neuroimaging techniques to demonstrate that, in patients, pHGG exhibit connectivity to a prognostic brain circuit associated with tumour incidence and anatomic progression (unpublished). This PhD project pairs genomic techniques with functional neuroimaging and intraoperative electrophysiological recordings of tumour-infiltrated cortex in children with pHGG to characterise the dynamic interplay between neuron-glioma circuits and tumour-microenvironmental interactions in the context of patient clinical trajectories. A particular focus is the analysis of pre- and post-resection neural activity to elucidate circuit remodelling in response to therapy.

Are you interested? Contact Darren 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 developed 3D models of gastro-intestinal cancers (precision cut tumour/tissue slices and paired organoids) to study early radiation (Xray and protons and drug combinations) effects on tumour/immune /microenvironment and inform how to construct improved radiation-drug combinations. We study the primary resistance to radiation in 3D models (spatial transcriptomics and organoids) to better understand resistance and refine 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 >20 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.

Our research focusses on glioblastoma, a universally fatal brain cancer. Rapid growth, diffuse infiltration, and therapy resistance result in median survival <15 months. Despite intense research, the biological processes driving glioblastoma initiation, invasion, and recurrence remain poorly understood. We have recently identified that glioblastoma activates brain injury programs that play a central role in tumour progression. As the tumour develops, it infiltrates the white-matter, leading to axonal loss through a modifiable, cell-autonomous process. Remarkably, modulating this pathway in preclinical models slows progression, improves neurological function, and extends survival. Depending on the candidate’s experience and interests they will build on this theme, focussing on novel approaches to early disease detection, mechanistic studies of neuron-glioma signalling, or analysis of local and global neural network function in the setting of infiltrating tumours. There is scope for wet-lab or bioinformatics/data focussed projects. The overall aim is to uncover actionable insights into glioblastoma biology.

Are you interested? Contact Ciaran by email.

5-year recurrence rates for stage I non-small cell lung cancers (NSCLCs) remain high at 20-30%. Emerging evidence suggests some patients may benefit from adjuvant chemotherapy. Current risk-stratification using genomic analysis and computational pathology cannot provide a comprehensive view of the tumour microenvironment (TME) and are subject to sampling bias due to tumour heterogeneity. Micro-CT allows non-destructive 3D imaging of the TME with 10-100 times higher resolution compared to clinical-grade CT. Serial histopathology slides can be reconstructed into 3D images as well, albeit labour intensive. By referencing the histopathology slides as ground truth, we will develop a deep learning model to learn histopathological features on the co-registered micro-CT image. This multimodal insight into the entire architecture and spatial relationships within the TME (e.g. growth patterns, immune infiltrates, vasculature), will help identify high-risk phenotypes that benefit from treatment intensification. This research will utilise skills within artificial intelligence, bioinformatics, and imaging-based biomarkers.

Are you interested? Contact Joseph by email.

We study cancer evolution and development of metastasis, from the perspective of the cancer cell and its microenvironment, but also the systemic whole-body manifestations, such as changes in body composition and cachexia. We combine radiological, genomic and transcriptomic analyses to study metastatic dissemination, as well as blood proteome and metabolome analyses to understand the biological correlates of cancer progression and poor prognosis.

This project applies single cell technologies (genomic and spatial transcriptomic) to the longitudinal TRACERx and PEACE studies for the phylogenetic analysis of metastatic initiation and dissemination, and the study of the tumor microenvironment interactions and immune evasion in metastasising clones.

Both TRACERx and PEACE allow for the integration of detailed clinical annotation in the context of drug resistance and aggressive lung cancer, and the development of methods to map metastasising clonal populations in space and time, and explore the impact of the immune microenvironment on metastatic cancer evolution.

Potential secondary supervisor: Anita Grigoriadis, KCL

Are you interested? Contact Mariam 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.

Clear cell gynaecological cancer (CCGC) has distinct molecular features, including a complex, immune-rich tumour microenvironment (TME). Our team has recently led the PEACOCC trial evaluating immune checkpoint inhibition (ICI) in CCGC and collected longitudinal tumour, blood and plasma samples from enrolled patients. PEACOCC met its primary endpoint but only 25% of patients responded and current clinical or molecular features cannot predict response.

We have a track record in analysing tissue samples from cancer patients to investigate molecular determinants of therapeutic response, including ICI. We recently showed that: (1) cytotoxic lymphocytes andantigen-presenting macrophages are key for patient’s response to ICI (2) the local TME regulates functionality of tumour cells and (3) tumour immunophenotypes stratify for treatment response.

Here we propose to investigate tumour-TME interactions and their impact on ICI outcome in patients from the PEACOCC trial to understand the mechanisms of response and potentially identify predictive biomarkers.

Potential secondary supervisor: Francesca Cicarelli, QMUL

Are you interested? Contact Rebecca by email.

Prostate cancer differs from many some cancers in that not all are universally dangerous. There are good and bad prostate cancers, currently defined by their “grade”. Many men with prostate cancer do not need treatment. We are increasingly confident that men with low grade cancer that do not need treating. However, some men with higher-grade cancer could also be managed in this way, whole others need early identification and immediate treatment to avoid death from prostate cancer. In this project, we will undertake a detailed spatial genetic analysis of low-grade cancer to identify specific genes that are turned on or off. We will compare these findings to higher-grade cancer to select men for conservative management. State-of-the-art spatial molecular techniques have only recently made it possible to analyse the detailed composition of tumours in this way. Students will work at the cutting edge of surgery, pathology, translational genomics and computational biology.

Are you interested? Contact Alastair by email.

Head and neck cancer is the sixth most common cancer worldwide. It accounts for approximately 900,000 cases and over 400,000 deaths per year. It is an understudied cancer, and due to HPV-prevalence is projected to undergo drastic growth over the next decade. Identification of biomarkers that enable early identification of individuals at high risk would enable screening, whilst understanding the specific biology of head and neck squamous cell cancer (HNSCC) would suggest potential therapeutic targets that suitable for different patient cohorts. This work will create a single, analysed dataset that presents the landscape of HNSCC, enabling bioinformatics and computational modelling work. This dataset will be available to the wider community but will also initiate new work within the collaborator network on the mechanisms of HNSCC carcinogenesis. This will translate this work into the clinical practice. In the UK, 10% of these cancers are not eligible for any routine molecular profiling and for the rest the current National Genomic Test Directory includes routine testing for 6 genes only.

Potential secondary supervisors: Teresa Guerrero Urbano, KCL; Alona Sosinsky, Genomic England; Benjamin Hall, UCL

Are you interested? Contact Matt by email.

Neuroendocrine/small cell prostate cancer (NEPC) is a lethal form of prostate cancer. There is a high response rate to Chemo-immunotherapy but nearly all patients will relapse although the mechanisms for this resistance are not well elucidated. RET is a receptor tyrosine kinase that is commonly translocated in NEPC and has been associated with immunotherapy resistance. RET inhibitors have shown promise but acquired resistance has tempered enthusiasm.

Using clinically curated biobank samples, we will characterise the RET expression and immune microenvironment of NEPC through spatial transcriptomics. To understand the short-term acquired immune resistance to chemo-immunotherapy we will use patient derived ex vivo explant model that we routinely use in the lab, and profile changes in response to treatment using spectral flow cytometry. We have a range of structureinformed novel RET tool compounds designed to circumvent resistance which we would aim to test in the explant model and could be used to design and develop dual-targeting (e.g. PD-1 and RET) therapeutics.

Potential secondary supervisor: Neil McDonald, Crick

Are you interested? Contact Mark 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.

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.

Professor McDonald’s lab has extensively studied the evolution of precancerous disease to cancer, focusing on Barrett’s oesophagus (BO), the only known precursor to oesophageal adenocarcinoma (OAC). In BO, the normal squamous epithelium is replaced by metaplastic columnar epithelium. Although BO is common in the UK, the progression rate to OAC remains low. However, OAC presents a significant clinical challenge due to its poor five-year survival rate. Therefore, it is critical to identify which BO patients are at high risk before cancer develops. Data from our CRUK Programme Foundation Award and the Cancer Grand Challenge has revealed a loss of oxidative phosphorylation (OxPhos) in epithelial and a gain in stromal mitochondria respectively of non-dysplastic BO patients prior to cancer progression. These findings suggest early metabolic changes in high-risk individuals. This project will investigate the mechanisms behind these alterations todevelop improved biomarkers for early detection and potential interventional strategies.

Potential secondary supervisor: Marco Novelli, UCL

Are you interested? Contact Stuart by email.

Phaeochromocytomas and paragangliomas (PPGLs) are rare neuroendocrine tumours that arise in the adrenal medulla (phaeochromocytoma) or paraganglia of the autonomic nervous system (paraganglioma). ~40% of PPGLs are inherited and develop in patients who carry a pathogenic germline variant in one of eighteen genes. Metastatic disease occurs in 15-25% of PPGLs and treatment options for metastatic PPGLs are limited with no means of predicting who is at risk of developing metastatic disease. We have collected >100 tumours and collated >400 tumour transcriptomes and stratified them as metastatic or not, along with DNA methylation data and global histone modification data captured with mass spectrometry. These data have facilitated the identification of candidate genes for metastatic behaviour. The tumour collection pipeline, the tumours already archived, and preliminary omics data provide a set of robust tools for identifying key features of metastatic tumour behaviour needed to develop biomarkers and improve tumour stratification for patients.

Are you interested? Contact Rebecca by email.

Our group investigates the molecular basis of lymphoma initiation and progression by characterizing tumour and immune heterogeneity, disease evolution to identify disease- and treatment-related biomarkers. We employ bulk tumour and single-cell multi-omic technologies, in vitro models, and computational tools, focusing on primary patient samples from late phase clinical trials and real-world cohorts.

This project will focus on mantle cell lymphoma (MCL), an aggressive non-Hodgkin lymphoma with variable clinical outcomes. Despite treatment advances, MCL remains difficult to manage due to the varied clinical spectrum, with some patients exhibiting indolent disease and others more aggressive forms. Leveraging samples from two key cohorts: the ZEBRA clinical trial (indolent MCL) and the UK MCL Biobank (nearly 600 patients encompassing the entire clinical spectrum), we aim to uncover tumour and immune heterogeneity underlying this variation. Additionally, the project will explore the use of liquid biopsies to monitor disease dynamics over time.

Potential secondary supervisor: Nicholas McGranahan, UCL

Are you interested? Contact Jessica 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.

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.

Myelodysplastic Syndrome (MDS) and Acute Myeloid Leukaemia (AML) are largely incurable. Innate immune dysfunction contributes to their development. Clonal haematopoiesis (CH) is frequently found in healthy individuals, involves MDS/AML-associated mutations and increases risk of MDS/AML 20–100-fold. These mutations (CH-MUT) also affect innate immune cells such as monocyte-macrophages, which are implicated in tumour growth, including lung cancer.

Research Questions:

1. How do CH-MUT alter macrophage function and anti-tumour responses?
2. How do they support survival and expansion of pre-leukaemic clones?
3. Can macrophage dysfunction be targeted at the pre-leukaemic stage to prevent progression?

Work Packages:

1. Functional profiling of CH-MUT and CH-WT macrophages from patient bone marrow in vitro and in organoids.
2. Assess impact of CH-MUT/WT macrophages on CH-HSPC expansion in vitro and zebrafish, and identify key pathways using multi-omics.
3. Validate candidate targets using molecular and drug screens in co-culture and zebrafish models.

Potential secondary supervisor: Elspeth Payne

Are you interested? Contact Lynn by email.

The Quezada Lab focuses on understanding the complex immunological landscape of the tumour microenvironment (TME) to develop precision, personalised T cell therapies for cancer. By dissecting the interactions between tumour cells, stromal elements, and diverse immune populations, the lab identifies key mechanisms that shape immune responses in cancer. Using advanced technologies such as single-cell transcriptomics and ex vivo system models, the lab characterises tumour-infiltrating lymphocytes (TILs) and their functional states. This knowledge informs the design of tailored immunotherapies, including natural and engineered T cells. The ultimate aim is to develop novel methods to expand tumour reactive T cells whilst armouring them overcome tumour-induced immunosuppression and enhance the efficacy of adoptive T cell therapy.

Are you interested? Contact Sergio by email.

Our lab’s vision is to weaponize the immune system to detect and intercept cancer at its earliest stages. We focus on T cell responses to pre-cancerous lesions, mapping how T cells recognize, circulate, and become regulated during early carcinogenesis. Our current work is developing a comprehensive pre-cancer immune atlas integrating single-cell and spatial transcriptomics to uncover conserved immune targets across multiple pre-cancer types. This computationally intensive project (70–100% dry lab) will build on this atlas to identify candidate targets for immune interception. These targets will then be refined using our spatial Xenium atlas of ~10 human pre-cancer types, with the potential for functional validation ex vivo in explant cultures, including with and without neoantigen stimulation. Our ambition is to develop precision immune-interception strategies to prevent progression to invasive cancer.

Are you interested? Contact James by email.

We aim to improve prostate cancer outcomes by generating fundamental biological knowledge to transform our understanding of early development of prostate cancer. Prostate cancer is heterogeneous and this impacts population-based screening, stratification and treatment. Despite the identification of prostate cancer-specific genomic alterations (e.g. PTEN), how these control cancer initiation is poorly understood. Moreover, we currently lack the ability to identify, prognosticate progression risk and prevent development of clinically-significant disease in at risk groups.

To pinpoint relevant early prostate cancer events, we identified PTEN^loss-associated transcriptomic and splicing changes but determining which are essential for progression to aggressive, clinicallysignificant cancer remains challenging due to a lack of in vivo models to test them in a timely manner.

We will use a combination of Drosophila genetics, 2D/3D mammalian models and patient samples to identify and functionally characterise prostate cancer initiation genes to be targeted in future integrated detection, prevention and stratification strategies.

Are you interested? Contact Paolo by email.

B cell lymphoma encompass a variety of cancers, which can be cured in a fraction of patients, while a large proportion of patients, mostly those with low-grade lymphoma, develop therapy resistance and ultimately succumb to their disease. Genomics and mutational burden underlying these diseases are unable to sufficiently explain this dichotomy, but an increasing amount of evidence indicates that the tumour microenvironment (TME) drives clonal evolution and resistance to therapies. This project aims at deciphering differences in the composition of the TME in low-grade, high-grade and transformed B cell lymphoma with a focus on mesenchymal stroma and T cells to understand responses to treatment and to ultimately improve treatment outcome for these patients. We employ spatial transcriptomics, highresolution microscopy and RNA-sequencing (single cell and bulk), combined with clinical trial data to identify different components of the TME in B cell lymphoma subsets which shape clinical responses to cancer therapies.

Potential secondary supervisor: Alan Ramsey, KCL

Are you interested? Contact Ingo 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 and can recur more than 10 years after diagnosis. 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 how the tumour microenvironment influences the risk of relapse in invasive lobular carcinoma. The project will involve the analysis of spatial transcriptomic data performed on samples from the GLACIER study where we have long term outcome data available. The aim will be to Identify changes in the microenvironment that predict recurrence and can differentiate between early and late relapse.

Potential secondary supervisor: Eric Sahai, Crick

Are you interested? Contact Elinor by email.

Our laboratory focuses on PI3K enzymes, elucidating their roles in both physiological and pathological contexts. Our efforts in developing PI3K-inhibitors have substantially contributed to the progression of clinically-approved PI3K-targeted therapies.

We discovered PI3Kδ as a leukocyte-enriched PI3K isoform with critical functions in lymphocytes. Our research also revealed that PI3Kδ-inhibition triggers an adaptive immune response against cancer. (Nature 2014, 2022). PI3Kδ-based immunotherapy approach is now in Phase II trials in lung cancer and melanoma.

Interestingly, PI3Kδ is also highly-expressed in some solid-tumours, such as melanoma, where its function is unknown. This is a critical question for identifying biomarkers to guide patient selection—specifically, whether PI3Kδ activity within cancer cells contributes positively or negatively to the efficacy of PI3Kδ-targeted cancer immunotherapy. We are addressing this question by basic science studies, in collaboration with PI3Kδ drug developers.

Other planned studies with clinical colleagues at the Cancer Institute cover alternative uses for PI3Kδ- inhibitors, including topical application and early cancer interception. We are also developing small-molecule PI3Kδ-activators for to build on our success of PI3Kα-activators (Nature 2023), for which we are currently exploiting the UCL/MRC IP for out-licencing and spin-out creation.

Are you interested? Contact Bart by email.

Our work focuses on understanding the molecular underpinnings of cancer-specific vulnerabilities to develop molecularly-targeted therapeutics of various modalities (i.e. small molecules, antibodies, ADCs). We use this knowledge to establish the best therapeutic approach using comparative pharmacology to identify contextspecific best-in-class molecules either as single agents (to establish proof-of-principle) or in combination when appropriate. Our main interest is in primary brain tumours, in particular glioblastoma. Our involvement with the ongoing world’s first adaptive platform multi-centre study for glioblastoma (https://news.cancerresearchuk.org/2024/10/23/3m-for-world-first-trial-to-revolutionise-brain-cancertreatment/) places us in a unique position to test new hypotheses from clinical observations and potentially provide rationale for new study arms.

Are you interested? Contact Igor by email.

Oncolytic viral therapy (OVT) is an emerging immunotherapy showing promise in both pre-clinical and clinical cancer studies. Our lab has focused on engineering oncolytic Vaccinia (VV) and Adenoviruses to treat diverse solid tumours.

We recently applied our OVT platform to treat recurrent glioblastoma and paediatric Diffuse Intrinsic Pontine Glioma (DIPG), demonstrating a favourable safety profile and encouraging signs of efficacy in clinical patients. However, durable clinical responses remain limited, underscoring the need to enhance anti-tumour immunity.

We have recently developed a novel, systemically deliverable VV that is effective across varioussolid tumour models, including orthotopic brain tumour and transgenic KPC pancreatic cancer. In this project the candidate of CRF will further improve this virus, by arming with cytokines and immune-modulating payloads like CD276-specific BiTEs (Bispecific T-cell Engagers) or novel immunomodulators in development in the Hiley lab (patent application in process), to overcome limitations of current OVT and immunotherapies. This approach is designed to elicit potent, selective anti-cancer immune responses and drive long-term remission in multiple solid tumours – including pancreatic, lung, and DIPG.

Potential secondary supervisor: Crispin Hiley, UCL

Are you interested? Contact Yaohe by email.

Whilst immune checkpoint inhibitors (CPIs) can cure cancers, these drugs also cause clinically significant immune toxicities. Unfortunately, very little is known about the biological mechanisms driving these immune related adverse events (irAEs) and to date has not been possible to predict who will develop irAEs. Thus, rather than rational prevention of irAEs in high-risk patients, treatment is often reactionary, delayed, empirical and at risk of impairing anti-tumour immunity.

As CPI-induced irAEs are organ specific (e.g., skin, gut, etc.), it is likely that tissue-resident immune cells, particularly T cells are key drivers. Access to these cells is a challenge, limiting our understanding of their biology. To unravel this, we will apply cutting-edge spatial imaging/transcriptomics, as well as 3D ex vivo patient-derived tumour models, to directly study of these cells in healthy, tumour and pre/post CPI-treated tissues. Understanding this biology will help to predict and more effectively treat organ specific irAEs.

Potential secondary supervisor: Sergia Quezada, UCL

Are you interested? Contact Yin by email.