Prof Ed Tate (Chemistry), Dr Holger Auner (Immunology and Inflammation), Dr Milon Mondal (Chemistry)

“Targeting ubiquitin processing in multiple myeloma: novel probes for Ubiquitin Specific Peptidase 30”

USP30 overexpression is strongly associated with drug resistant lymphoma, leukaemia and multiple myeloma, in which apoptotic pathways are dysregulated through altered expression of BCL-2. USP30 depletion sensitizes cancer cells to BH3-mimetics, making it a potential target for cancer therapy, however, its endogenous substrates and regulation remain poorly understood. This project will look to develop activity-based probes to better understand USP30 biology and potential as a therapeutic target

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Dr Sylvain Ladame (Bioengineering), Prof Simak Ali (Surgery and Cancer), Prof Laki Buluwela (Surgery and Cancer)

“Bespoke Peptide Nucleic Acid Optical Probes for the In Situ Detection of Mutations in Breast Cancer Tumour Sections”

This proposal aims to carry out a proof-of-principle study to demonstrate the use of novel Peptide Nucleic Acid (PNA)-based probes for the in-situ detection of specific DNA mutations in pathological sections of breast cancer.

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Dr Marco Di Antonio (Chemistry), Prof Robert Brown (Surgery and Cancer)

“Unravelling epigenetic targets and synthetic lethality mechanisms by means of light-controlled editing of DNA methylation in cancer cells”

This application is proposing to develop a novel chemical platform that enables the installation or removal of DNA-methylation, in a spatially and temporally controlled fashion, allowing the dynamics and heterogeneity of epigenetic mechanisms to be examined for the first time.

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Prof Paul Freemont (Infectious Disease), Dr Richard Kelwick (Infectious Disease), Dr Marko Storch (Life Sciences)

“AL-PHA biosensors: a low-cost platform for the detection of exosome-associated cancer biomarkers”

This proposal is looking to further develop the next generation of Advanced proteoLytic detector PolyHydroxyAlkanoates (AL-PHA) beads – a set of low-cost, biodegradable, bioplastic-based protease biosensors – in order to detect exosome-associated metalloproteinases as a biomarker for lung cancer.

Prof Hector Keun (Surgery and Cancer), Dr Peter DiMaggio (Chemical Engineering)

“Opening a new window into the interplay between tumour metabolism, PARP biology and therapy response via metabolic flux analysis and a novel chemical proteomics workflow”

This project aims to provide proof-of-concept for a novel convergence science platform to gain new insights into the biological function and regulation of Poly-ADP-ribose polymerases (PARPs) in cancer cells. In addition, it will aim to identify novel determinants of PARP inhibitor response in cancer cells and how these can be exploited therapeutically.

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Dr Matthew Grech-Sollars (Surgery and Cancer), Dr Rebecca Quest (Department of Imaging, Imperial College Healthcare NHS Trust), Dr Kyriakos Lobotesis (Imperial College Healthcare NHS Trust), Dr Neal Bangerter (Bioengineering)

“MR Fingerprinting Brain Tumours–A Pilot Study”

The overall aim of the project is to implement novel cutting-edge quantitative MRI techniques (MR Fingerprinting) at Imperial College to advance clinical imaging research techniques including radiomics and the use of more accurate machine learning tools. We will be exploring the use of MR Fingerprinting (MRF) in brain tumours, which are known to be heterogeneous and therefore ideal for studying the ability of MRF to discriminate between regions of tumour which are more aggressive and aid clinical diagnosis.

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Dr Iros Barozzi (Surgery and Cancer), Dr Sung Pil Hong (Surgery and Cancer)

“Dissection of Chemotherapy-Induced Tumour Heterogeneity at a Single-Cell Level”

This project is aimed at investigating how a single cell from a heterogeneous tumour adapts to chemotherapeutic drugs and becomes resistant using Single-cell-RNA-sequencing (sc-RNA-seq). It will provide new biomarkers for monitoring and targeting the emergence of resistant clones, while offering insights into the common and unique phenotypic changes induced by different chemotherapeutic agents.

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Prof Hugh Brady (Life Sciences), Prof Matt Fuchter (Chemistry), Prof Iain McNeish (Surgery and Cancer)

“Natural Killer (NK) cell immunotherapy for ovarian cancer”

This project will seek to optimise a novel NK cell-based immunotherapy approach to treat ovarian cancer. This includes the development of compounds and engineering approaches to enhance the ability of NK cells to kill cancer cells.

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Prof Alex Porter (Materials), Dr Nelofer Syed (Brain Sciences), Dr Theoni Georgiou (Materials)

“Polymersome formulations for effective drug delivery to brain tumours”

Treatment option for glioblastoma (GBM), are severely limited and survival remains very poor with existing treatments. This project will aim to generate proof-of-concept that polymersomes bearing chemotherapeutic drugs conjugated to the FDA approved BBB targeting molecule L-DOPA can target, cross the BBB and significantly shrink the size of glioblastoma (GBM) tumours in vivo.

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Prof Edward Tate (Chemistry), Prof Iain McNeish (Surgery and Cancer), Dr Scott Lovell (Chemistry)

“Unlocking the KLK activome in epithelial ovarian cancer: biomarker discovery and target validation”

Epithelial ovarian cancer (EOC) represents a growing women’s issue worldwide. Several studies have revealed that kallikrein-related peptidases (KLKs), a family of serine proteases, are aberrantly expressed in EOC patient specimens and may play a role in cancer progression. This project will use a recently prototyped technology platform using activity-based probes to determine the activity of KLKs in EOC and their potential actionable activities for driving disease progression and drug resistance.

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Dr Amanda Cross (Surgery and Cancer), Dr Kevin Monahan (Medicine)

“Surveillance for individuals at high-risk of colorectal cancer: Phase 1 - Developing a national database of Lynch Syndrome patients as a model to establish an effective surveillance strategy for high-risk groups”

Lynch Syndrome (LS) is the most common hereditary ColoRectal Cancer (CRC) syndrome and arises as a result of germline mutations in mismatch repair genes. The lifetime CRC risk associated with LS is as high as 80% without surveillance, however, LS is ‘under-recognised, under-diagnosed and under-managed’. This project will aim to create a national database of people with Lynch Syndrome (LS) to ensure that these patients receive appropriate colonoscopy surveillance consistent with national guidelines by providing an efficient call/recall system for hospitals.

Dr. Constandina Pospori (Life Sciences), Prof Cristina Lo Celso (Life Sciences), Prof Mauricio Barahona (Mathematics)

“Investigating population dynamics and lineage hierarchy relationships in leukaemic blasts with distinct proliferative and immunomodulatory profiles in vivo: the contribution of leukaemia heterogeneity to disease propagation”

This project will explore the hypothesis that tumour heterogeneity may be, rather than a by-product of malignant clone competition, in fact essential for tumour development. By combining intravital imaging, flow cytometry, RNAseq data and mathematical modelling this project will investigate the lineage hierarchy between PDL1-low and –high leukaemic blast subsets and understand if the PDL1‐high blasts function as an accessory but essential subset, creating an immunoprivileged microenvironment.

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Dr Vessela Vassileva (Surgery and Cancer), Prof Eric Aboagye (Surgery and Cancer), Dr Kathrin Heinzmann (surgery and Cancer), Dr Ali Ashek (Medicine). Dr Yean Chooi (Bioengineering)

“Targeting hypoxia to improve delivery of tumour targeting antibodies in pancreatic cancer”

Hypoxia has been identified as a major adverse feature of pancreatic cancer, and is associated with resistance to therapy and poor prognosis. This project will evaluate whether targeting hypoxia in pancreatic tumours can improve the delivery of targeted radionuclide therapy using an antibody directed against carcinoembryonic antigen (A5B7), which is expressed in the majority of pancreatic cancers (85-90%), but not normal cells. The hypoxia pro-drug, TH-302, will be used to selectively kill hypoxic tumour cells, in combination with A5B7, to evaluate whether this can achieve improved tumour perfusion and vascular flow, and radiosensitisation to targeted radionuclide therapy in pre-clinical models of pancreatic cancer.