Research
Chemical and cellular basis of immunological drug reactions
I have developed practical and conceptual means to combine aspects of genetics, cell biology and chemistry in order to study the fundamental principles of drug and chemical hypersensitivity. This unique approach has allowed me to study immunological reactions from man to molecule and back again. A deeper understanding of such basic scientific principles can on the one hand inform clinical practice and on the other safe drug development in the Pharmaceutical Industry. Active innovative projects funded by the MRC and Pharma that highlight real-life impact include
i. Delivery of personalized drug treatment strategies to allergic patients. This allows us to make an impact clinically, by translating laboratory findings into patient care.
ii. Development of a toolbox of assays for drug immunogenicity prediction. Working alongside Pharma we have a pathway for application of the assays in a real-life setting.
iii. As leaders in mechanistic immunopharmacology, we are regularly approached by Pharma to explore the immunogenicity of drugs undergoing clinical trials.
I have co-authored 200 peer-reviewed publications including 15 articles in Journal of Allergy and Clinical Immunology (impact factor [IF] 14.3), 7 in Allergy (IF 14.9), 4 in Hepatology (IF 17.4), 4 in Journal of Investigative Dermatology (IF 8.6). I have acted as a project lead on important university programmes including MRC CDSS, and IMI MIP-DILI & ARDAT. I have established programmes with over 40 national and international clinical centres to explore mechanisms of adverse drug reactions. External knowledge exchange is evidenced through (i) foundation of the European T-cell immunity network in Allergy, (ii) award of International and European Marie Curie Actions Incoming Fellowships, (iii) hosting of visiting fellows from Asia (China, South Korea and Thailand), South America (Mexico) and Europe (UK, France, Germany, Spain), (iv) appointment as visiting Distinguished Professor at Shandong Provincial Institute of Dermatology and award of a Chinese Overseas Talent Programme. Prizes awarded for research excellence including the prestigious American Chemical Society young investigator award, the British Pharmacological Society Novartis prize and ISSX New Investigator Award. 45 PhD students (39 as primary supervisor) have been awarded degrees under my supervision.
Research Interest 1
The major aim of my research is exploration of the chemical and cellular basis of hypersensitivity reactions to drugs and chemicals. More specifically, these studies attempt to relate drug metabolism and covalent binding of chemicals to protein to the basic immunology and functioning of immune cells. These studies provide further insight into the critical question of how low molecular weight chemicals cause serious tissue injury in man.
• My research group has published 65 full research articles and/or reviews in internationally recognised journals.
Specific projects
1. Investigation of the phenotype, specificity and cytokine profile of drug-specific T-cell lines and clones from hypersensitive patients
2. Characterization of the role of metabolism in drug hypersensitivity reactions
3. In vitro induction of drug-specific T-cell responses using blood from drug-naïve human donors
4. Investigation of the chemical and cellular basis of contact sensitisation mediated by exposure to hair dyes
5. Investigation of the molecular and chemical basis of differential (Th1, Th2 and Th0) drug-specific lymphocyte activation
6. Transcriptional profiling of T-cell clones from hypersensitive patients
7. Exploration of the interaction of drug & chemical haptens with protein
8. Evaluation of the T-cell stimulatory capacity of peptide vaccines in patients with pancreatic cancer
9. Investigation of the immunological mechanisms of drug-induced allergic events in patients with cystic fibrosis
10. Development of an animal model of drug-induced allergic disease
Research grants
Development of screening approaches to assess to intrinsic immunogenicity of drugs and novel chemicals
BIOTECHNOLOGY & BIOLOGICAL SCIENCE RESEARCH COUNCIL, GLAXOSMITHKLINE (UK)
March 2018 - May 2021
Characterization of the binding of dapsone(metabolite) binding antigens to HLA-B*13:01 and the activation of cytotoxic CD8+ T-cells
DEPARTMENT FOR BUSINESS, ENERGY AND INDUSTRIAL STRATEGY (BEIS) (UK)
March 2018 - March 2020
Drug Hypersensitivity in Cystic Fibrosis - development of diagnostic and management strategies.
MUKOVISZIDOSE INSTITUTE (GERMAN CF FOUNDATION)
March 2018 - February 2020
Characterization of T-cell responses to drugs in HLA-genotyped donors
HANMI PHARMACEUTICAL (SOUTH KOREA)
September 2017 - August 2018
CASE Studentship Josh Gardner
ASTRAZENECA LIMITED (UK)
October 2018 - March 2023
Definition of the role of T-cells in drug-induced liver injury
JANSSEN PHARMACEUTICALS (BELGIUM)
January 2018 - September 2019
Bench Fees for Alanood Abdulshkoor A Howsawi (201781289)
ROYAL EMBASSY OF SAUDI ARABIA CULTURAL BUREAU IN LONDON (UK)
January 2024 - January 2025
Interim support for ISARIC4C Clinical Characterisation Protocol (CCP) activation for acute severe hepatitis in children of unknown cause
MEDICAL RESEARCH COUNCIL
June 2022 - September 2024
Bench Fees for Ghazi Mohammed D Dhahi (201594689)
ROYAL EMBASSY OF SAUDI ARABIA CULTURAL BUREAU IN LONDON (UK)
November 2021 - September 2024
A personalised approach to manage adverse reactions to CFTR modulator therapy in patients with cystic fibrosis
MEDICAL RESEARCH COUNCIL
November 2022 - October 2025
COVID-19 vaccine responses in follicular lymphoma: impact of frontline therapy options
UNIVERSITY OF BIRMINGHAM (UK)
April 2021 - September 2022
COVID-19 vaccine responses in follicular lymphoma: impact of frontline therapy options (PETReA)
BLOOD CANCER UK (UK)
May 2021 - November 2022
How well do new vaccines against COVID-19 work in people with follicular lymphoma
UNIVERSITY OF BIRMINGHAM (UK)
January 2021 - March 2021
Translational Relevance of the Stimulator of Interferon Genes (STING) pathway and viral infection in Follicular Lymphoma
NORTH WEST CANCER RESEARCH INCORPORATING CLATTERBRIDGE CANCER RESEARCH (UK)
February 2023 - February 2026
Identification of apalutamide-speciifc T-cell responses in patients with skin rash
JANSSEN PHARMACEUTICALS (BELGIUM)
September 2021 - March 2027
Accelerating Research & Development for Advanced Therapies (ARDAT)
BAYER AG (GERMANY), EUROPEAN COMMISSION
November 2020 - October 2025
Application of in vitro cell culture platforms to study the intrinsic immunogenicity of MK3207 and MK0974
MERCK & CO., INC. (USA)
December 2016 - April 2019
Bench Fees for Luis Castrejon.
CONSEJO NACIONAL DE CIENCIA Y TECNOLOGIA (MEXICO)
February 2008 - January 2010
Definition of chemical and immunological signals associated with the development of contact dermatitis.
BRITISH SKIN FOUNDATION (UK)
January 2006 - December 2008
Signalling and function of immunomodulatory biologics
REPUBLIC OF IRAQ MINISTRY OF EDUCATION🚩
October 2014 - September 2017
Quantitative high-throughput proteomics for biomedical research.
MEDICAL RESEARCH COUNCIL
March 2005 - March 2008
Bridging and accelerating the translation of novel scientific findings for health and wealth gain
MEDICAL RESEARCH COUNCIL
March 2014 - August 2015
Chic-FILI—Definition of the chemical and immunological characteristics of flucloxacillin-induced liver injury
EUROPEAN COMMISSION
September 2012 - August 2013
The immunological response consequences of metabolic drug activation by dendritic cells.
WELLCOME TRUST (UK)
April 2006 - April 2009
A prospective investigation of drug-specific B-cell responses in allergic patients with cystic fibrosis
UNIVERSITY OF ILORIN (NIGERIA)
December 2011 - November 2014
Molecular basis of T-cell triggering in patients with drug allergy
THE HIGHER COMMITTEE FOR EDUCATION DEVELOPMENT IN IRAQ (HCED) (IRAQ)
October 2012 - September 2016
Development of an in vivo mouse model to study the role of metabolism in drug-induced cutaneous hypersensitivity reactions
ASTRAZENECA LIMITED (UK)
October 2009 - September 2013
A prospective investigation of β-lactam allergy in patients with cystic fibrosis to define drug immunogenicity
CYSTIC FIBROSIS TRUST (UK)
December 2011 - August 2016
Development of an in vivo model of drug-induced cutaneous toxicity.
WELLCOME TRUST (UK)
July 2001 - September 2001
The role of drug-specific T-cells in allergic reactions to drugs
ROYAL EMBASSY OF SAUDI ARABIA
October 2011 - September 2014
Mechanistic basis of dapsone hypersensitivity
ROYAL EMBASSY OF SAUDI ARABIA
July 2014 - June 2017
The Chemical and Cellular Basis of Drug Hypersensitivity.
WELLCOME TRUST (UK)
January 2000 - January 2004
The role of peripheral and liver-associated T lymphocytes in pathogenesis of alcholic liver disease.
ROYAL LIVERPOOL AND BROADGREEN UNIVERSITY HOSPITALS NHS TRUST (UK)
May 2004 - October 2005
Research collaborations
Andrea Cavani
University of Rome
Characterization of skin resident T-cells
Stefan Martin
University of Frankfurt (Germany)
Development of in vitro T-cell priming assays
Dr Daniel Peckham
The University of Leeds
Immune mechanisms of drug allergy in patients with cystic fibrosis
Werner Pichler
Aachen University
T-cell projects
L Trepanier
University of Wisconsin
T-cell experiments in experimental models
JF Nicolas
ADER Fez
Developing models of drug allergy