Areas of interest
Drug discovery, drug development and tropical pharmacology. Understanding the chemical, molecular and cellular basis of drug action and drug resistance in tropical pathogens with an emphasis on human malaria, TB and more recently the Neglected Tropical Diseases (NTDs). This fundamental information is then employed in the rational design and evaluation of novel chemotherapeutic agents and in improving the effectiveness of existing chemotherapeutic agents. Linked to this interest there is a focus on understanding fundamental pathogen-specific biological processes with a view to identifying unique targets for chemotherapy.
Stephen Ward graduated in Pharmacology and Physiology from Aston University in 1979 and obtained his PhD in Biochemical Pharmacology from Liverpool University in 1984. He spent the next two years as a Senior Research in Medecine Fellow at Vanderbilt University in Tennessee USA before returning to the Liverpool School of Tropical Medicine as the Wolfson Lecturer in Tropical Pharmacology. In 1990 he moved to a lectureship in Pharmacology in the University of Liverpool and was awarded a chair in Pharmacology in 1999. He returned to the Liverpool School of Tropical Medicine in 2000 as Walter Myers Professor and Head of Molecular and Biochemical Parasitology and was appointed as deputy Director of the School in 2001.
Research in Medecine
The research focus has been towards understanding the mechanisms of action and resistance to anti infective drugs and the translation of basic science knowledge into new drugs for malaria, TB and more recently NTDs. Over the past 20 years the Drug Discovery Unit in Liverpool has developed a molecule to man initiative aimed at translating basic scientific knowledge into products. This has resulted in the international registration of two drugs, the progression of a further four molecules into human clinical trials and progression of six molecules into formal pre-clinical evaluation.
Artemisinin mechanism of action and resistance remains a research focus. Using filed isolates from S.E. Asia displaying the reduced in vivo clearance phenotype alongside laboratory selected lines we are applying a range of molecular and biochemical approaches to characterise these parasites. Linked to these studies is a medicinal chemistry programme that has a) generated novel probe peroxides that are being used as chemical biology tools to identify drug targets within the malaria parasite and b) delivered a new candidate antimalarial drug for development with the potential of delivering a single dose cure. The group is adopting a systems pharmacology approach to understanding drug action and has established a range of technology platforms that are generating multi-parameter data sets for all current and investigational antimalarial molecules in the public domain. The project is configured to provide novel insights into important aspects of parasite biology as well as contributing towards our drug discovery programmes. The group also has active research programmes focussed on energy metabolism in malaria parasites, the folate pathway and the functional characterisation of parasite transporters. In each case research is focussed in understanding the underlying biochemistry and cell biology but with the view of exploiting this information through our drug discovery activities.
The group, in collaboration with Dr Biagini, is focussed on defining redox systems and energy metabolism in replicating and non-replicating TB. This work has generated a full drug discovery programme, currently at lead optimisation, targeting a novel enzyme target that is essential in all parasite cell cycle states. Linked with the malaria programme a systems pharmacology approach is also being used to define mechanisms of action of current and investigational anti-TB molecules.
As part of the AWOL initiative, co-ordinated by Professor M Taylor, we have generated a series of drug-like hit molecules through an extensive library screening exercise. The search for additional leads is on going with over 2million compounds having been screened to date.. Hits have been triaged and prioritised and are in the process of lead optimisation involving iterative rounds of medicinal chemistry and testing in the in vitro and in vivo nematode screens and counter screens. The research delivered two new candidate molecules for onward development. Supporting the better deployment of existing AWOL treatment strategies the group is also adopting a detailed PK/PD approach to evaluating the best monotherapy and combination therapy options currently available for immediate use.