Our research

Neuroblastoma is a childhood malignancy that still poses a severe challenge to paediatric oncologists. Despite tremendous progresses in the understanding of the molecular causes of the disease, the outcome of high risk, metastatic neuroblastoma is still poor, because of lack of effective drugs targeting neuroblastoma molecular drivers. Given the young age of patients, aggressive chemotherapy is often associated with long lasting sequelae such as retarded growth and cognitive impairment. Thus, the use of less toxic therapies, such as immunotherapy, is particularly advantageous in this setting. Immunotherapy is an important tool in the fight against neuroblastoma.

Compared to standard chemotherapeutic treatments, immunotherapy interventions are less toxic and potentially more effective. For example, immunotherapy with the antibody GD2 has been a game changer in children with high risk neuroblastoma, with around half of patients receiving the antibody showing stable disease or tumour regression after five years. Another form of immunotherapy in which patient T cells are engineered to fight tumour cells has also shown good potential. 

However, many patients do not benefit from immunotherapies because their lymphoid organs contain cells that antagonise the antitumour immune response. The hypothesis that we would like to validate in this study is that Prozac, or other anti-depressant drugs, could be used to inactivate cancer-induced immune cells, improving the efficacy of immunotherapies. In a recently published study, we have shown that Prozac can dramatically reduce metastatic disease in a mouse model of neuroblastoma and preliminary evidence suggests that it could do so by acting both on the cancer and immune cells. Thus, antidepressant drugs could be advantageously used in children with neuroblastoma to not only enhance immunotherapy, but also inhibit tumour growth at the same time.

Cancer immunotherapy works by helping the body's immune system identify and destroy cancer cells. While these treatments have transformed outcomes for some patients, many cancers can evade immune detection or develop resistance, meaning that not all patients benefit equally. Understanding why this happens is a major challenge in cancer research.

Our research investigates how cancer cells interact with the immune system and how tumours develop mechanisms to avoid immune attack. We focus on a process called antigen presentation, which allows immune cells to recognise abnormal proteins produced by cancer cells. Many tumours disrupt this process, helping them escape detection and continue growing despite treatment.

Using carefully selected mouse models of melanoma, colorectal cancer, and breast cancer, alongside studies of human tumour samples and advanced imaging technologies, we examine how changes within tumours and their surrounding environment influence immune responses. We also evaluate new and existing immunotherapies, including immune checkpoint inhibitors, cancer vaccines, and T cell-based therapies, to understand why some treatments succeed while others fail.

The overall goal of this work is to identify biomarkers that can predict whether a patient is likely to respond to immunotherapy and to develop new strategies that improve treatment efficacy. These discoveries may support earlier and more accurate monitoring of treatment response, helping clinicians make better-informed decisions and enabling more personalised approaches to cancer care.

Animal studies are essential for understanding the complex interactions between tumours and the immune system throughout the whole body. However, we are committed to the principles of Replacement, Reduction and Refinement (the 3Rs), using non-animal alternatives wherever possible, minimising animal numbers through advanced imaging approaches, and continually refining procedures to maximise animal welfare.

Sewage effluents contain a vast mixture of chemicals, some of which have been shown to alter the hormone (endocrine) systems of wild fish living in habitats receiving these effluents. This project aims to assess the current frequency and severity of endocrine (hormone) disruption in wild fish (Roach; Rutilus rutilus) living in English and Welsh rivers in connection with the concentrations of known endocrine disrupting chemicals coming from sewage effluents and the sewage treatment technologies used in these locations.

Project outputs will include data on the frequency and severity of endocrine disruption in wild fish from rivers downstream of sewage effluents across England and Wales. For some of these locations, data collected during this project will be combined with comparable data collected in the 1990s, early 2000s and 2017 surveys to assess whether the level of endocrine disruption in wild fish has increased, decreased or stayed the same. Analysis of the frequency, severity, and any possible temporal trends will be assessed in relation to the concentrations of endocrine disrupting chemicals measured at the sampling locations, and with the sewage works treatment technologies employed upstream of these sites. This data will inform recommendations to the Water industry and the Environment Agency for future strategies to reduce endocrine disrupting chemical pollution entering the aquatic environment.

Our research explores how the immune system can both protect us and, when it goes wrong, harm us. Inflammation is essential for fighting infection and repairing injury, but when it fails to switch off properly it can drive diseases such as stroke, heart disease, dementia and cancer. Our work uses zebrafish and mouse models to study immune cells, blood vessels and clotting in action, helping us understand why inflammation can become damaging, particularly as we age and in conditions such as sickle cell disease, settings where the risk of harmful blood clots rises sharply. Studying these processes in carefully designed animal models lets us answer questions that cannot yet be addressed directly in people, and test whether ‘pro-resolving’ treatments, which encourage the body to actively switch inflammation off, can guide it back towards healing rather than harm. The transparent zebrafish larvae also offer a way to study inflammation in real time that may, in time, help reduce the number of higher animals such as rodents used in this kind of research. Our long-term aim is to discover new therapeutic strategies that reduce harmful inflammation and clotting, support healthier ageing, and improve outcomes for patients with inflammatory and vascular diseases.

Brunel researchers are using established mouse models of Friedreich's ataxia (FRDA), a rare inherited neurodegenerative disorder, to better understand disease mechanisms and develop new treatment strategies. FRDA leads to progressive damage to the nervous system and heart, resulting in severe disability and reduced life expectancy. Although omaveloxolone is now available as the first approved treatment for FRDA, significant unmet clinical needs remain and additional therapies are needed to improve outcomes for patients.

Our research focuses on evaluating a range of complementary therapeutic approaches, including antioxidant-based therapies, iron chelators, metabolomics-guided interventions and gene therapy strategies. These approaches aim to address the underlying molecular and cellular changes associated with FRDA, including oxidative stress, mitochondrial dysfunction, metabolic abnormalities and reduced frataxin expression. Animal models play a critical role in determining the safety and effectiveness of these treatments before they can progress to clinical trials in humans.

The ultimate goal of this research is to develop therapies that can complement existing treatments such as omaveloxolone or provide alternative approaches that are more effective in slowing, halting or reversing disease progression. The knowledge gained from these studies will contribute to improving the quality of life and long-term outcomes of individuals living with FRDA

At Brunel University of London, we are investigating the molecular mechanisms underlying a group of rare genetic disorders known as ciliopathies, in which the primary cilium is the principal affected organelle. Ciliopathies are multisystem disorders that affect numerous organs and tissues, leading to a broad spectrum of clinical manifestations. Our research focuses on understanding the function of genes associated with these disorders using genetically engineered mouse models. In particular, we study the retina and central nervous system, with an emphasis on genes responsible for Bardet–Biedl syndrome (BBS), one of the most common syndromic ciliopathies. Both patients with BBS and corresponding mouse models develop progressive retinal degeneration, resulting in severe vision loss and ultimately blindness. 

To address this, we are developing gene therapy approaches aimed at restoring the function of disease-causing mutated genes. We design and optimise therapeutic constructs and viral vectors capable of delivering functional copies of mutated genes to affected tissues. By re-establishing normal gene expression, these therapies aim to preserve photoreceptor survival, halt retinal degeneration, and prevent further vision loss.  In addition to retinal disease, we investigate the neurological manifestations of ciliopathies, particularly the obesity that arises from disrupted hypothalamic homeostasis and impaired leptin signalling. Our gene therapy strategies target specific regions of the brain to restore neurometabolic regulation, with the goal of preventing or reversing excessive weight gain.  These research programmes have progressed beyond preclinical studies and into Phase I/II clinical trials. Patients are currently receiving these therapies, providing the opportunity to evaluate the safety and efficacy of treatments that were initially developed and validated in our mouse models. Together, our work aims to translate fundamental discoveries in cilia biology into effective gene therapies for patients affected by these devastating inherited disorders.