Professor Dean Naisbitt BSc, PhD

Professor Pharmacology & Therapeutics

    Research

    Research Overview

    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 - February 2025

    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

    External: University of Rome

    Characterization of skin resident T-cells

    Stefan Martin

    External: University of Frankfurt (Germany)

    Development of in vitro T-cell priming assays

    Dr Daniel Peckham

    External: The University of Leeds

    Immune mechanisms of drug allergy in patients with cystic fibrosis

    Werner Pichler

    External: Aachen University

    T-cell projects

    L Trepanier

    External: University of Wisconsin

    T-cell experiments in experimental models

    JF Nicolas

    External: ADER Fez

    Developing models of drug allergy