Research and scholarship
Research and scholarship
Research theme: Therapeutics
In our team we are exploring drug discovery and development, as well as bioengineering of peptides and antibodies for biomedical application in cancer and infectious diseases. To achieve our goals, we use interdisciplinary and multidisciplinary approaches such as analytical (bio)chemistry, medicinal chemistry, mammalian and microbial cell cultures, immunoblotting, flow cytometry, fluorescence scanning electron microscopy, epigenetic and proteomics analysis.
Novel therapy development
Medicines from nature have long been used for the therapy of various kinds of disease. Even today, many drugs are from or derived from natural products. Penicillin is the first antibiotic discovered in the UK; paclitaxel isolated from yew trees in the USA is a well-known chemotherapy drug for the treatment of different cancers including ovarian, breast and lung cancer; artemisinin (qinghao su, 青蒿素) discovered in China is the first-line therapy against malaria.
Due to the development of multi-drug resistance in cancers and microbial pathogens, there is an urgent need to discover and develop new medicines with novel mechanisms of action to combat these diseases. Currently, we are exploring anticancer, antibacterial and antimalarial compounds from natural sources including Chinese medicinal plants and African medicinal plants and marine organisms. Our aim is to discover new bioactive natural products, make their analogues via semi-synthesis or biotransformation, and understand their mechanisms of action and pharmacokinetics. We hope to develop hit compounds to lead compounds and to clinical trial candidates, and eventually as safe and effective medicines.
F. Uche, et al. Bioorg. Med. Chem. Lett., 2018, 28, 1652
Collaborators: Dr Alan Richardson, Prof. Paul Horrocks (Keele); Prof. Tim Claridge, Prof. James McCullagh, (Oxford); Dr Vidushi S Neergheen-Bhujan (Mauritius).
Antibody-drug conjugates (ADCs) are emerging as a highly potent and targeted hybrid class of biopharmaceuticals for the treatment of cancer. ADCs comprise an antibody, a linker and a cytotoxic drug. By combining the highly specific targeting capabilities of a monoclonal antibody raised against a particular tumour marker with the cytotoxic drug, ADCs allow for focussed discrimination between healthy and diseased tissue. To date, four ADCs have received approval for treatment of various cancers; these are gemtuzumab ozogamicin; brentuximab vedotin, and trastuzumab emtansine. Many other ADCs are at different stages of clinical development. Novel ADCs against different types of cancers are highly desired. Our aims are to design and make novel ADCs using highly toxic natural products as payloads to treat ovarian cancer with minimal side effects.
Collaborators: Dr. Alan Richardson, Dr. Sarah Hart, Prof. Murray Brunt.
Biomedical Engineering
Medical device related infections constitute up to 60% of health care associated infections due to biofilm formation. Biofilms protect cells from environmental stresses, and host immune responses. It has been reported that 99.9% of bacteria grow as aggregated "sessile" communities attached to surfaces, rather than as "planktonic" or free-floating cells in liquid. As a consequence, antibiotics act against bacteria in biofilms less effectively. Thus, antimicrobial peptides, including plant-derived cyclotides, designed and synthetic peptides are considered to be promising agents against multidrug-resistant bacterial biofilm infections. Antibacterial coating has become a favourable approach to tackle bacterial pathogens on the implant surfaces. Therefore, we aim to use novel antimicrobial peptides to bind to metallic surfaces of implant in order to address biofilm-associated infection.
P. Cao, et al. Int. J. Mol. Sci. 2018, 19, 793
Collaborators: Prof. Ying Yang, Dr. Sarah Hart (Keele), Prof. Chengqing Yuan (China).
