Photo of Dr Ian Copple

Dr Ian Copple BSc (Hons), PhD, FHEA

MRC Senior Fellow / Senior Lecturer Pharmacology & Therapeutics

    Research

    Research Interests

    My research group focuses on understanding mechanisms that underlie cellular stress (especially Nrf2) responses in the context of drug toxicity and disease, and exploiting this knowledge to improve our ability to treat patients in a number of settings. We have a particular interest in liver disease and drug-induced liver injury, but are open to collaboration in other areas.


    Click here to see all of our publications in PubMed.


    Some of our previous achievements in the areas of Nrf2 pharmacology and toxicology include:

    # Demonstrating that pharmacological activation of Nrf2 can enhance liver regeneration following surgery - PubMed

    # Revealing the transcriptional landscape of the Nrf2 pathway in primary human hepatocytes - PubMed

    # Detailing the regulatory roles of Nrf2 in the kidney, in which Nrf2 inducers have recently emerged as novel therapeutic agents - PubMed

    # Identifying a novel interaction between Keap1 and the multi-functional protein p62/SQSTM1, which regulates the degradation of Keap1 and activity of Nrf2 - PubMed

    # Defining the chemical modification of Keap1 by Nrf2-activating compounds in living cells, a key aspect of the 'stress sensing' capacity of the Nrf2 pathway - PubMed


    Examples of our current research include:

    # Understanding the benefits and risks of modulating Nrf2 activity in different disease contexts.

    # Determining the value of monitoring perturbation of the Nrf2 pathway for the prediction of drug toxicity earlier in the drug development process.

    # Using novel pharmacological tools to modulate the activity of Nrf2 and other transcription factors/proteins, as part of investigations into new ways of treating disease.


    Current group members:
    Rowena Sison-Young (Post-doc)
    Giusy Russomanno (Post-doc)
    Georgina Gregory (PhD student)
    Hannah Coghlan (PhD student)
    Rob Young (PhD student)


    Previous group members:
    Shiva Forootan (Post-doc)
    Lawrence Howell (Post-doc)
    Charles Winiarski (Post-doc)
    Adedamola Olayanju (Post-doc)
    Victoria Watson (Post-doc)
    Ben Chan (PhD student)
    Tobias Bunday (PhD student)
    Lucia Livoti (PhD student)
    Adeeb Rehman (PhD student)
    Fiona Mutter (PhD student)
    Luke Shelton (PhD student)
    Jason Yau (MRes student)
    Sean Duffy (MRes student)
    Jessica Clarke (MRes student)
    Pak Him Chiu (MRes student)
    Olivia Matthews (BPS summer student)

    .

    Research Grants

    Unravelling species differences in stress responses to inform the selection, and reduce the use, of animals in preclinical drug safety testing

    ASTRAZENECA LIMITED (UK)

    October 2021 - September 2025

    Liverpool Cancer Research Institute Research Development Fund

    NORTH WEST CANCER RESEARCH INCORPORATING CLATTERBRIDGE CANCER RESEARCH (UK)

    March 2022 - March 2023

    TransQST: Translational quantitative systems toxicology to improve the understanding of the safety of medicines

    EUROPEAN COMMISSION

    January 2017 - August 2022

    Preclinical evaluation of Nrf2 inhibition as a means to improve chemotherapeutic efficacy in patients with pancreatic cancer

    PANCREATIC CANCER RESEARCH FUND (UK)

    February 2016 - January 2020

    Mechanistic investigation and risk:benefit analysis of the use of brusatol as a novel adjuvant for overcoming cisplatin resistance in bladder cancer

    NORTH WEST CANCER RESEARCH INCORPORATING CLATTERBRIDGE CANCER RESEARCH (UK)

    February 2016 - February 2018

    Regulation of irinotecan anti-cancer pharmacology by Nrf2 – Implications for current use and potential for improved efficacy

    NORTH WEST CANCER RESEARCH FUND

    February 2014 - February 2016

    Definition of chemical and molecular mechanisms of cytotoxicity induced by next-generation synthetic endoperoxide antimalarials, through the use of novel imaging-based approaches

    ROYAL SOCIETY (CHARITABLE)

    September 2011 - October 2011

    Research Collaborations

    Prof Scott Friedman

    External: Ichan School of Medicine at Mount Sinai

    Evaluation of Nrf2 activators in a model of non-alcoholic steatohepatitis

    Prof Magnus Ingelman-Sundberg

    External: Karolinska Institute

    3D in vitro human liver models

    Mr Steve Fenwick / Mr Hassan Malik / Mr Rob Jones / Mr Rafa Diez Neto

    External: Aintree University Hospital

    Human liver tissue and primary hepatocytes

    Prof Bob van de Water / Dr Ciaran Fisher

    External: Leiden University / Certara Inc

    Quantitative systems toxicology modelling of drug-induced liver injury

    Prof Nagy Habib

    External: MiNa Therapeutics

    Evaluation of saRNAs as novel pharmacological tools

    Prof Harish Poptani

    Internal

    Preclinical imaging (MRI, bioluminescence)

    Prof Andy Jones

    Internal

    Computational biology of stress response pathways

    Prof Chris Goldring

    Internal

    Mechanisms and biomarkers of adverse drug reactions

    Prof Stuart Forbes

    External: University of Edinburgh

    Pharmacological modulation of liver regeneration

    Prof Peter Friend

    External: University of Oxford

    Ex vivo liver perfusion

    Prof Carolyn Young

    External: Walton Centre

    Pharmacodynamic biomarkers of Nrf2

    Dr Keiko Taguchi / Prof Masayuki Yamamoto

    External: Tohoku University

    Role of Nrf2 in resistance to drug toxicity