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Kinases, the enzymes that catalyse phosphorylation events, have been implicated in hundreds of different diseases, and hold rich promise for drug development. In 1998, The University of Dundee developed the first systematic assay to analyse the selectivity of protein kinase inhibitors, termed `kinase profiling'. This technology has been crucial for the development of new therapeutic drugs targeting protein kinases. In order to promote drug discovery in the area of kinases, the Division of Signal Transduction Therapy (DSTT) was formed and provides a unique collaboration between the University and six of the world's leading pharmaceutical companies.
The protein kinase PKB (also known as Akt) is a key regulator of cell proliferation and survival that is commonly dysregulated in human cancers. Work at the University of Dundee in the late 1990s identified key components of this signaling pathway and established the mechanism by which PKB becomes activated through phosphorylation. Structural studies at the University provided important insights for the design of small molecules permitting targeted inhibition of this enzyme. PKB is a firmly established focus for pharmacological intervention and several clinical trials are underway testing the antineoplastic activity of PKB inhibitors in a variety of cancers.
Research conducted at the University of Bristol between 1994 and 2013 has led to major commercial impact through industry investment in cancer therapies that target a family of transporter proteins (MCTs) identified and characterised by Professor Halestrap and his colleagues. Halestrap has worked directly with AstraZeneca, a leading global biopharmaceutical company, to integrate the Bristol-based research into their own research programme to elucidate the mode of action of a group of novel immunosuppressive agents that target MCT1. Subsequent ongoing collaborations have underpinned AstraZeneca's development of these drugs for cancer chemotherapy, with clinical trials of their compound AZD3965 underway, as well as investment in a new cancer drug discovery programme targeting the MCTs.
Thousands of people across the world with a genetic predisposition (HNPCC) to bowel cancer, together with the population at large, have benefited from research on aspirin and dietary fibre undertaken at the University of Bristol since 1993. Clinical trials involving the Bristol group show that the incidence of bowel cancer has fallen in HNPCC patients who take aspirin. Moreover, aspirin use after diagnosis of bowel cancer has reduced colorectal cancer mortality. Furthermore, a high fibre diet also lowers the risk of bowel cancer. These studies led to national public health initiatives (such as the `five-a-day' campaign) that have been instrumental in increasing public awareness of the importance of aspirin and dietary fibre in reducing the risk of bowel cancer, and in establishing international guidelines on dietary advice.
Our research has underpinned the work of Celldex Therapeutics and other US based companies, in developing a vaccine directed against hCGβ for the adjuvant treatment of epithelial cancer. A number of Phase I trials indicated an improvement in survival of vaccinated patients and Phase II trials began for bladder cancer where early data showed promise by improving the survival time. This has had a significant impact on these patients, and has the potential to extend the life of many millions of cancer sufferers (around 32% frequency of hCGβ secretion by carcinomas). Our research input has helped prove the technology and further trials are awaiting finance.
Ataxia telangiectasia (A-T) is an inherited disease affecting multiple systems in the body, causing severe disability and death. Work led by Professor Malcolm Taylor at the University of Birmingham has been central to the biological and clinical understanding of this disease, from the identification of the gene responsible to the clarification of related conditions with different underlying causes. As a result of this work, within the 2008-13 period, his laboratory has been designated the national laboratory for clinical diagnosis of A-T — a service also offered internationally — and has also changed national screening policy for breast cancer, following his confirmation of the increased risks of A-T patients and those who carry a single copy of the gene for this type of tumour. Furthermore, he has contributed in a major way to patient support for this condition.
Diabetes research at University of Ulster (Ulster) addresses the unmet need of industry for new and more effective commercially applicable approaches for diabetes therapy. We have generated a new class of innovative peptide therapeutics resulting in a strong portfolio of intellectual property, significant international recognition, financial investment and job creation, with commercialisation through Ulster's technology transfer company, Innovation Ulster (IUL), and the Ulster start-up company, Diabetica Ltd. Our substantial interactions with industry have resulted in the licensing and further development of our international patents on stable incretin peptides for diabetes and, through our discovery of their positive effects on cognition, for treatment of Alzheimer's disease. This work has provided industry with new and commercially viable approaches to significantly improve the lives of people with diabetes and related neurodegenerative disease.
Cancer research at the University of Salford focuses on developing new and improved treatments for cancer, particularly for children with cancer, demonstrating the following impact:
As sophisticated proteomics methodologies are increasingly embraced by both academics and industry across the globe, growth in this area is set to explode. The University of Dundee has a leadership position in quantitative proteomics technology, through the expertise of Professor Angus Lamond. Dundee Cell Products Ltd is a University of Dundee spin-out company that was created to commercialise life sciences technology and reagents, and to exploit technology and expertise in proteomics developed at the College of Life Sciences. As of 2013, DCP offers >5,000 research products and six contract research services, centred around quantitative proteomics.
Cancer is a widespread deadly disease; annually, one million new breast cancers are diagnosed globally. Endometriosis is a poorly understood disorder, with 80 million patients worldwide. Current therapies for both are inadequate and discovery of new drugs is critical. The Bath group has pioneered identification of new targets and designed two "first-in-class" clinical drugs. The Bath/Imperial College spin-out company Sterix (subsequently acquired by a major pharmaceutical company) has translated them into patients and to the pharmaceutical industry. The steroid sulfatase inhibitors, Irosustat and J995 have entered eighteen clinical trials worldwide in patients with these hormone-dependent diseases, with several ongoing since 2008. Disease was stabilised for cancer patients; the advanced clinical evaluation of both drugs is in progress.