Our research aims to improve the effectiveness of chimeric antigen receptor (CAR)-T cell immunotherapies for both adult and childhood cancers. A major barrier to successful treatment of solid tumours is the tumour microenvironment (TME), which restricts the trafficking, infiltration and function of CAR-T cells. This project will combine the complementary expertise of Prof. Arnold in TME biology and immune regulation with that of Dr Fisher in the development of cellular therapy approaches.
The Fellow will investigate how specialised cellular populations within the TME regulate T-cell entry into tumours and how these pathways can be manipulated to enhance CAR-T cell infiltration and anti-tumour activity. Using clinically relevant models of human cancer, including paediatric malignancies, the project will explore strategies to improve the delivery and infiltration of cellular immunotherapies in solid tumours. This highly translational research programme will provide training in tumour immunology, CAR-T cell engineering, and preclinical cancer models.
Potential collaborator: Jonathan Fisher, UCL
Are you interested? Contact James 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 with a developing interest in in vivo CAR-T technologies. 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 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 facilitates our early phase clinical studies such as the CRUK funded pCAR19 study for refractory B-cell lymphomas and the Blood Cancer UK funded TriMM CAR T cell study for multiple myeloma due to open at KCH in 2027.
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 apply this model to brain tumour tasks where there is less data. One such task is 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 1000-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 50-100 patients with PSC driven CCA in the context of prospectively documented genomic and clinical trial level data.
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.
Lipids are essential components of all cellular membranes. Human cells produce, maintain and metabolise thousands of different lipids, a diversity that approaches that of proteins. Despite this central role, it is not well understood what physiological requirements underlie this lipid diversity. The goal of our group is to investigate this question, using tools and techniques we develop.
It is well known that lipid metabolism is dysregulated in cancer cells. For example, the fatty acid desaturase SCD1 is upregulated in multiple cancers. However, attempts to target lipid metabolism in this therapeutic space have had mixed success, likely because we do not fully appreciate the complexity of lipid regulation. Our group has encouraging data in cultured cells showing that rebalancing lipid metabolism rescues disease phenotypes, including those caused by SCD1 perturbation. We are now ready to move this approach into more clinically relevant systems, making this a suitable project for a clinician-scientist.
Are you interested? Contact Ulrike 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.
Cancer vaccines are a new generation of immunotherapy. They showed promising increases in cure rates after the resection of early-stage cancers. Current cancer vaccine technologies first identify mutations in the genome and subsequently computationally predict which ones encode for neoantigens, which are peptides with altered sequences that can bind to autologous class I HLA molecules. These are then encoded into a personalised RNA vaccine. We have shown by mass spectrometry analyses of colorectal cancer (CRC) immunopeptidomes that computational neoantigen predictions overestimate the number of presented antigens, and that the number of presented neoantigens is low in many CRCs. This project addressed both limitations: We will assess whether next-generation mass spectrometry immunopeptidomics technologies can discover antigen that can be recognized by T cells more accurately than computational predictions (Aim 1). This could lead to more effective cancer vaccine designs. Secondly, we will investigate which conventional cancer therapies increase the presentation of neoantigens but also of peptides derived from human endogenous retroviruses (HERVs) (Aim 2). Combining therapies which increase the presentation of such cancer-specific antigens with cancer vaccines should improve vaccine effectiveness.
Potential collaborator: George Kassiotis, Francis Crick 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. 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.
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.
The Hill lab focuses on the transforming growth factor beta (TGF-β) ligand family. These ligands control embryonic development and adult tissue homeostasis, and deregulated signalling is associated with diseases such as cancer, fibrosis and the Marfan syndromes. We have recently shown that Activin A has both tumour promoting and tumour suppressing effects in mouse models of pancreatic cancer. Most importantly, using an antibody that neutralises Activin A activity we have shown in the context of a mouse model of pancreatic cancer, where the tumour cells are null for SMAD4 (a common occurrence in human pancreatic cancer), treatment of mice with an anti-activin A antibody increases the survival of the mice. Moreover, this is improved further upon treatment with immune checkpoint inhibitors. Having focused on primary tumours we now want to explore the role of activin and TGF-β signalling in pancreatic cancer metastasis to the lung and liver.
Potential collaborator: Debashis Sarker, KCL
Are you interested? Contact Caroline by email.
The appalling survival of patients with primary glioblastoma, <15 months on average, is underpinned by diverse molecular changes within the tumour microenvironment. Recent research has identified cellular state plasticity, immune-glioma dynamics, and activation of injury-like programmes as key determinants of tumour progression and resistance. Despite these advances in understanding, approaches that harness and integrate the growing range of multimodal datasets remain limited.
The overarching aim of this project is to integrate multimodal datasets, including pathology and spatial-omics data from pre-clinical models and patient tissues, together with AI-based computational approaches, to dissect the spatiotemporal associations within the tumour microenvironment, including the relationship between neuronal damage, immune response and transcriptomic heterogeneity in glioblastoma.
The project will be tailored to the applicant expertise, integrating preclinical and human oncological and pathological data to develop computational models that may provide new insights into fundamental tumour and microenvironment biology, laying the foundation for future translational applications.
Are you interested? Contact Ciaran by email.
Lung cancer metastatic progression remains difficult to predict and treat. This research project will leverage clinically annotated TRACERx, TRACERx-EVO and PEACE cohorts to investigate how tumour evolution, chromosomal instability, spatial immune context and circulating biomarkers shape metastatic dissemination.
The CRTF project will integrate longitudinal clinical annotation, multi-region tumour genomics at single cell resolution, tumour microenvironment spatial profiling and blood-based ctDNA/TCR analyses to identify biological features associated with aggressive metastatic progression and targetable features for potential novel therapeutics.
The work is well suited for a clinician-scientists as it links clinically meaningful disease trajectories with quantitative cancer evolution, tumour microenvironment analysis and translational biomarker development. The long-term aim is to improve risk stratification, surveillance and treatment personalisation for patients with lung cancer. Through this project, the clinical fellow will develop skills across medical oncology, computational biology, spatial profiling and liquid biopsy analyses.
Potential secondary supervisor: Anita Grigoriadis, KCL
Are you interested? Contact Mariam by email.
Patients with mismatch repair-deficient (dMMR) colorectal cancer can achieve dramatic responses to immune checkpoint inhibition, yet surgery remains the standard of care even in patients with complete tumour eradication. The NEOPRISM-1 study demonstrated unprecedented pathological complete response rates following neoadjuvant pembrolizumab and showed that patients with complete molecular response remained disease-free after surgery, providing the first evidence that molecular response may identify patients who no longer require surgical resection. Building on these findings, NEOPRISM-2 will develop and prospectively validate a cutting-edge biomarker-guided strategy for organ preservation using ultrasensitive circulating tumour DNA (ctDNA), TCR immune profiling and longitudinal molecular monitoring. The successful candidate will combine clinical trial methodology, molecular pathology, liquid biopsy technologies and advanced statistical modelling to redefine how cure is assessed after immunotherapy. This project aims to establish the evidence required to safely replace surgery with precision surveillance in selected patients, transforming the management of colorectal cancer.
Potential secondary supervisor: Benjamin Werner, QMUL
Are you interested? Contact Marnix 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.
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.
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 analysis1-2 of low-grade cancer to identify specific genes that are turned on or off. We will compare these findings to higher-grade cancer3-4 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.
Potential collaborator: Mieke van Hemelrijck, KCL
Are you interested? Contact Alastair by email.
The current diagnostic and prognostic approach in head and neck cancer does not utilise the latest molecular techniques and prognosticators available in the clinical setting. NHS patients do not currently benefit from these advances. Many techniques have been shown to be superior in terms of diagnosis and predicting prognosis.
This project aims to understand cancer evolution in the context of HPV-positive (a rapidly rising subset) and HPV-negative head and neck cancers. Working with the largest multimodal datasets available, we will develop multimodal deep learning models combining molecular analysis, histopathology and radiology to predict key prognostic factors.
The aims of the project are:
- Benchmark AI supported pathology analysis against manual expert lead analysis
- Create a digital pathology pipeline to analyse pathology slides
- Integrate omics, pathology, radiology data to create a multimodal deep learning model to better understand cancer evolution and predict prognosis in head and neck cancer
Potential secondary supervisors: Christopher Banerji, KCL
Are you interested? Contact Matt 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.
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.
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.
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.
Head and neck squamous cell carcinoma (HN-SCC) carries poor survival despite aggressive multimodality treatment. Our group has shown that intratumoural Fusobacterium is associated with improved HN-SCC survival and that Fusobacterium-derived butyrate drives tumour cytotoxicity through histone deacetylase inhibition (HDACi) in vitro. We are now characterising how Fusobacterium shapes the tumour microenvironment, encompassing immune cell infiltration, spatial gene expression and SCFA biosynthesis, and whether salivary Fusobacterium serves as a non-invasive surrogate for intratumoural bacterial load. Our work integrates clinical cohort data, shotgun metagenomics, NMR metabolomics, RNAscope, and spatial transcriptomics. A CRTF joining this programme will work at the intersection of translational microbiology and clinical oncology, contributing to biomarker development and mechanistic understanding of microbiome-cancer interactions with direct implications for immunotherapy and pharmacological HDACi treatment stratification.
Are you interested? Contact Miguel 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 PTENloss-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.
Our research focuses on how interactions between malignant B cells and the tumour microenvironment drive lymphoma progression, immune evasion and treatment resistance. This joint project brings together Dr John Riches’ expertise in metabolic pathways sustaining germinal centre-derived lymphomas, including follicular lymphoma, diffuse large B-cell lymphoma and Burkitt lymphoma, with Dr Alan Ramsay’s expertise in lymphoma-driven remodelling of lymph node (LN) fibroblast and immune compartments into tumour-supportive niches.
The project will define how stromal metabolism regulates lymphoma growth and anti-tumour immunity. Building on discoveries of lymphoma metabolic dependencies and our demonstration that aggressive lymphoma reprogrammes immunosupportive fibroblastic reticular cells (FRCs) into cancer-associated fibroblast-like ‘LN_CAFs’, we will test whether these pathways drive stromal corruption. Using genetically engineered mouse models, organotypic co-cultures and human lymphoma samples, we will examine effects on extracellular matrix remodelling, immune-cell infiltration and treatment response, identifying therapeutic targets and rational treatment combinations for patients with lymphoma.
Potential collaborator: Alan Ramsay
Are you interested? Contact John 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 collaborator: Eric Sahai, Francis Crick Institute, Louise Jones, QMUL
Are you interested? Contact Elinor by email.
We study the biology of key mutations found in Acute Myeloid Leukaemia (AML) and how these can be therapeutically targeted. We use CRISPR-Cas9 screens, next-generation sequencing, organoid models, and collaborate widely in the development of targeted protein degraders and more recently CAR-T cells.
Mutated nucleophosmin (NPM1c) is the most common recurrent mutation in AML. Recently, it was shown that NPM1c can be detected on the surface of AML cells. However, what controls NPM1c trafficking or surface expression is undefined.
We are currently using a CRISPR screen to identify key genes and pathways that control surface NPM1c expression. We aim to develop a binder to mutant NPM1c that can form the basis for CAR-T, bi-specific antibody, or antibody drug-conjugate. We aim to connect these research themes by testing our therapeutics on patient samples and organoids, pharmacologically exploiting the pathways identified in our CRISPR screens to enhance NPM1c surface expression and killing.
Potential secondary supervisor: Lynn Quek, KCL
Are you interested? Contact Rob 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, prevent and treat organ specific irAEs.
Potential secondary supervisor: Teresa Marafioti, UCL
Are you interested? Contact Yin by email.