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Ian Copple

Professor Ian Copple
BSc (Hons), PhD, FBPhS, FHEA

Research

StressResponse Lab

Research in the StressResponse Lab focuses on understanding mechanisms that underlie cellular stress responses in the context of the beneficial and adverse effects of medicines. These stress responses include the oxidative stress response, endoplasmic reticulum (unfolded protein) response, DNA damage response and autophagy.

Our goal is to harness the increasing understanding of these pathways to enhance the treatment of patients in a number of disease settings, by improving the effectiveness and/or reducing the toxic side effects of drugs. We have a particular interest in liver disease and drug-induced liver injury, but are open to collaboration in other areas.

We are a diverse team currently comprising 4 PhD students, 3 post-docs and 1 technician from different backgrounds. We have a culture of transparency, ethical responsibility and openness. Several past and present members of the group have won prizes for their work from national and international societies (see 'Group Members' below).

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Current Research & Past Achievements

Examples of our current research include:

# Understanding the benefits and risks of modulating the Nrf2 oxidative stress response in different disease contexts.
# Establishing robust means of monitoring Nrf2 activity and its therapeutic modulation in patients.
# Determining the role of Nrf2 in drug toxicity and its value as a risk marker in the drug development process.

Some of our past achievements 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 p62/SQSTM1, which regulates the degradation of Keap1 and activity of Nrf2 - PubMed
# Defining the chemical modification of sensor cysteine residues in Keap1 by Nrf2-activating compounds in living cells - PubMed

Check out all of my group's publications on PubMed and Google Scholar.

Group Members

Current group members (L-R):

# Giusy Russomanno (Post-doc)
# Hannah Coghlan (PhD student)
# Rob Young (PhD student)
# Olivia Harris (PhD student)
# Rowena Sison-Young (Post-doc/HLRF manager)
# Georgina Gregory (Post-doc)

# Karolina Kwiatkowska (PhD student; not shown)
# Ben Austin (Part-time technician; not shown)

In addition, since 2013 I have been primary supervisor for:

# 5 post-docs
# 7 PhD students
# 5 MRes students
# 1 MSc student
# +20 BSc research project students

Achievements of current/previous group members:

# 2024: Giusy Russomanno – Post-doc poster prize, British Toxicology Society annual congress.
# 2023: Hannah Coghlan – Oral communication prize, British Toxicology Society annual congress.
# 2023: Hannah Coghlan – EUROTOX Gordon Research Conference travel award.
# 2023: Giusy Russomanno – Poster prize, ISMIB Institute away day.
# 2022: Hannah Coghlan – Basic science presentation prize, Department postgraduate research day.
# 2022: Benjamin Chan – Oral communication prize, Association of Upper Gastrointestinal Surgeons annual scientific meeting.
# 2019: Lucia Livoti – Oral communication prize, British Toxicology Society annual congress.
# 2019: Benajmin Chan – Oral communication prize, Liverpool & North West Surgical Society annual meeting.
# 2019: Benjamin Chan – Oral communication prize, Association of Upper Gastrointestinal Surgeons annual scientific meeting.
# 2016: Olivia Matthews – British Pharmacological Society summer studentship.

Example destinations of previous group members:

# Tobias Bunday (PhD student) -> Translational Scientist, Sygnature Discovery
# Adedamola Olayanju (Post-doc) -> Senior Scientist, Manchester BIOGEL
# Fiona Mutter (PhD student) -> Post-doc, University of Greifswald, Germany
# Charles Winiarski (Post-doc) -> Business Development Manager, Manchester Inward Investment Agency
# Luke Shelton (PhD student) -> Post-doc, Radboud University Medical Center, the Netherlands
# Olivia Matthews (BPS undegraduate summer student) -> PhD student, University of Ediniburgh

Research grants

Cross sector experience award

THE ACADEMY OF MEDICAL SCIENCES (UK)

September 2024 - August 2025

Biomarker discovery to enable the non-invasive monitoring of NRF2 activator therapies in humans

INNOVATION LAUNCHPAD NETWORK+

July 2025 - December 2025

A new mechanism of redox regulation in Ser/Thr protein kinases

BIOTECHNOLOGY & BIOLOGICAL SCIENCE RESEARCH COUNCIL

March 2023 - February 2026

A platform to support the pharmacological targeting of Nrf2 in humans

MEDICAL RESEARCH COUNCIL

January 2023 - December 2027

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

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 Magnus Ingelman-Sundberg

    Karolinska Institute

    3D in vitro human liver models

    Dr Tom Kensler

    Fred Hutch Cancer Center

    Nrf2 pharmacology & biomarker discovery

    Dr Ciaran Fisher

    GSK

    Quantitative systems toxicology modelling of drug-induced liver injury

    Prof Carolyn Young

    Walton Centre

    Pharmacodynamic biomarkers of Nrf2

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

    Aintree University Hospital

    Human liver tissue and primary hepatocytes

    Prof Andy Jones

    Computational biology of stress response pathways

    Prof Chris Goldring

    Mechanisms and biomarkers of adverse drug reactions