Centre for Inflammation Research

Dr Gwo-tzer Ho

Research Theme in a Nutshell: Science to medicine: Inflammatory triggers to tissue repair in IBD.

Dr Gwo-tzer Ho

Principal Investigator and Honorary Consultant Gastroenterologist

  • Centre for Inflammation Research

Contact details

 

Research Theme in a Nutshell:

Science to medicine: Inflammatory triggers to Tissue Repair in IBD

My research is focused on two main questions:

1.  What are the molecular factors that drive and maintain the abnormal musocal inflammation in Crohn's Disease (CD) and Ulcerative Colitis (UC)?

2.  How do we translate this understanding to develop new, and to improve current, medical treatments for CD and UC?

Group Members

  • Claire Adams (ECAT Clinical Fellow - 2nd supervisor with Dr Calum Bain)
  • Bill Brownlee (Postdoctoral Scientist)
  • Alex Cavanagh (JSPS Clinical Research Fellow)
  • Shaun Chuah (Clinical Research Fellow - MD)
  • Lisa Derr (MARVEL Trial Manager)
  • Broc Drury (Research Assistant)
  • Thomas Fenton (Postdoctoral Scientist)
  • Lena Fischer (Postdoctoral Scientist)
  • Doirrean Gordon (MRC iCASE PhD Student - 2nd supervisor with Professor Marc Vendrell)
  • Rebecca Hall (Clinical Research Fellow - MD)
  • Gareth Rhys Jones (Wellcome Trust Intermediate Fellow and Honorary Consultant Gastroenterologist)
  • Rahul Kalla (Consultant Gastroenterologist and Senior Fellow)
  • Katherine Lewis (MARVEL Trial Support Officer)
  • Alix MacDonald (Trial Manager for MiniMarvel)
  • Jila Nazari (MUSIC Data Science Manager)
  • Ross Porter (AF Research Fellow)
  • Beena Poulouse (MUSIC Clinical Research Nurse)
  • Duncan Rutherford (CSO Clinical Research Fellow - PhD)
  • Emily Thompson (PhD Student - 2nd supervisor with Professor Marc Vendrell)
  • Emma Ward (MUSIC trial manager)
  • Robert Whelan (MRC Precision Medicine PhD student)
  • Michelle Wilson (Research Fellow for Mini MARVEL)

Patient Public Involvement Team

  • Kris Gourlay
  • Kris Mcguire (CIR and Patient and Public Involvement Representative)
  • Jon Rysdale (Patient Public Involvement Representative)

Edinburgh IBD Science Group

  • Calum Bain (Centre for Inflammation Research, CIR)
  • Susan Bodie (Business Development, BQ4)
  • Jennifer Cartwright (CIR)
  • David Dorward (Department of Pathology, RIE)
  • Ian Dransfield (CIR)
  • Emily Gwyer Findlay (CIR)
  • Paul Henderson (RHSC)
  • Neil Mabbott (Roslin Institute)
  • Adriano Rossi (CIR)
  • Silke Salavati (Roslin Institute)
  • Craig Stevens (Napier University)
  • Emily Thomson (CIR and PhD representative)
  • Marc Vendrell (CIR) 
  • David Wilson (Royal Hospital of Sick Children, RHSC)
  • Chengcan Yao (CIR)

Our Clinical Trials Team

  • Lisa Derr (Trial Manager for MARVEL)
  • Alix MacDonald (Trial Manager for MiniMARVEL)
  • Emma Ward (Trial Manager for MUSIC)
  • Beena Poulose (Clinical Research Nurse)
  • Katherine Lewis (Trial Support Worker)
  • Jila Nazari (Database Manager)
  • Michelle Wilson (Research Associate for MiniMARVEL)

Our friendly group meets every 3-4 months to discuss collaborative ideas and scientific data. Please contact if interested in joining.

Background

Crohn's disease (CD) and ulcerative colitis (UC) are common chronic inflammatory bowel diseases (IBD) with significant impact on morbidity, mortality and socio-economic costs. The global prevalence is increasing sharply with projected global disease burden of 20-30 million IBD cases by 2025. Present best therapies are based on the narrow principle of inhibiting downstream inflammatory pathways (eg, cytokines and inflammatory cell migration). Complete mucosal healing (total resolution of inflammation and restoration of full mucosal restitution) however, is achieved only in 50% in our best treatment. My work is focused on identifying and developing novel therapeutic approaches in IBD.

Research Overview

My overarching research aim is to translate new knowledge of immune and inflammatory mucosal mechanisms into new therapeutic approaches in IBD.

I work very closely with dedicated IBD clinicians, biologists, immunologists and drug development teams with a strong focus on direct studies on human IBD along with in vivo colitis work. Major mechanistic themes are:

  1. Gut derived mucosal damage-associated molecular patterns (DAMPs)
  2. Mitochondrial dysfunction and ROS-signalling
  3. Metabolic programing of the mucosal immune response
  4. Active reparative mechanisms with novel targets focused on inflammatory monocytes-macrophage and T-cell trafficking.

Find out more by watching our Let's Talk About Health public lecture from 2020:

Video: Healing the damaged gut in inflammatory bowel diseases
A recording of the Let's Talk About Health public lecture given on 19 February 2020, talking about the perspectives of a medical researcher, IBD patient and PhD student on current IBD research at the Centre for Inflammation Research.

 

Video: IRR Discovery Series: Dr Thomas Fenton
Dr Thomas Fenton, Visiting Scientist at the Centre for Inflammation Research, discusses a method he has developed which will give researchers a new way to analyse the intestinal immune system.

Dr Thomas Fenton, Visiting Scientist at the Centre for Inflammation Research (CIR), discusses a method he has developed which will give researchers a new way to analyse the intestinal immune system. Co-Lead for the Gut Research Unit at CIR, Dr Gwo-tzer Ho, also reflects on the discovery.

 

Our current projects

GI-DAMPs (CCUK-Genentech-Guts Charity UK): We seek to understand how mitochondrial DAMPs are released and how they activate the downstream inflammatory pathways (TLR9 and FPR1). We aim to find new therapeutic targets to accelerate the resolution of inflammation as an adjunct to current immune-suppressive treatments (@GI-DAMPs).

MARVEL (Jon Moulton Foundation): Mitochondrial antioxidant therapy to resolve inflammation in Ulcerative colitis (MARVEL) trial, a UK-wide randomized double-blind placebo-controlled trial using oral MitoQ (from February 2020). This builds directly from our primary scientific work; we are very excited to translate our science with this Phase II trial to test the potential of mitochondrial protective therapy in human IBD (@MarvelTrial).

MiniMARVEL (Jon Moulton Foundation): Phase 2b RCT into mitochondrial antioxidant therapy in children with early-onset Ulcerative Colitis in partnership with Professor David Wilson (RHSC)

MUSIC (Helmsley Charitable Trust): Mitochondrial DAMPs as mechanistic biomarkers of mucosal inflammation in Crohn's disease. We are generating a large deep endophenotyped IBD prospective cohort with longitudinal analysis of mucosal healing in centres from Edinburgh, Glasgow and Dundee - Music Study.  Based on this, we aim to translate DAMPs signals as stratifying approach to future new therapies in IBD.

Defining gut macrophage heterogeneity in CD (Wellcome Trust/ECCO): Using transcriptomics and epigenomic profiling approach as the first step to define the monocyte-macrophage populations during inflammation and resolution in Crohn's disease.

Pro-R in IBD (Chief Scientist Office/MRC/ERC): Working together with Emily Findlay (T-cell immunologist), Calum Bain (macrophage biologist), Adriano Rossi (deputy director of Centre for Inflammation Research), Ian Dransfield (leukocyte biologist) and Marc Vendrell (translational chemist), we have a program of inter-connected studies that are focused at accelerating repair in the IBD gut.

IBDIMAGE - Disruptive fluorescent technologies for inflammatory bowel disease. Lead: Dr Marc Vendrell. Developing novel biomarker technologies for IBD.

The effects of ageing on the gut immune function: with Professor Neil Mabbot.

The role of musocal-associated microbiome in the resolution of inflammation in IBD: with Professor Mick Watson.

The role of immunometabolism of monocyte-macrophage behavour: with Dr Calum Bain and Dr Gareth Rhys Jones.

Mitrochondrial function in intestinal gut stem cells: with Dr Laura Greaves, Newcastle Mitrochondrial Unit and Dr Mairi McLean, Dundee.

 

The following PDF provides a brief visual summary of this group’s current research.

 

You can view a full catalogue of graphical research summaries for each group in the Centre for Inflammation Research by visiting our Research page.

Visit CIR’s Research page

Biographical Overview

I trained in Medicine in Glasgow (MBChB 1997 and MRCP 2000), and moved to Edinburgh for my PhD with Jack Satsangi (2000-2003). I completed my specialty training in gastroenterology and internal medicine in Edinburgh (2003-2008) and was awarded an MRC Clinician Scientist Fellowship award (2009-2015) where I trained under Balfour Sartor in University of North Carolina, Chapel Hill, USA focusing on mucosal immunology in IBD. In 2018, I set up the Edinburgh IBD Science group and then the Gut Research Unit in CIR (2019).

With a strategic translational focus on human experimental work, my program supports a comprehensive portfolio of work across Scotland from basic discovery science to Phase 2 clinical trials in adults and children with IBD.

I continue to care for individuals with IBD working as an active consultant gastroenterologist at the Western General Hospital.

Healing the damaged gut in IBD: from the doctor, scientist and the patient - Let's Talk about Health Public Lecture Series, February 2020

Bowel disease study points to new therapies for lifelong conditions – Dr Gwo-tzer Ho’s recent study discussed on BBC Radio Scotland, May 2018 

Mitochondrial DNA as ancient danger signals in IBD – Dr Gwo-tzer Ho's interview for Inflammatory Bowel Disease journal, February 2018

Could the cause of inflammation be in our own cells? – Dr Gwo-tzer Ho's work in Crohn's and Colitis UK 10-year Research Report

Precision Medicine in Inflammatory Bowel Disease – American Journal of Gastroenterology interview with Editor Professor Lacy

Gene that affects cell power supply may hold key to bowel disease – Interview with Mhairi Stuart, BBC Scotland Radio and STV News (May 2017)

Faulty energy supply and leaky gut – a new potential cause for IBD – Press coverage (Times, Scotsman, Daily Mail +15 other national and international media

Current Committee/Editorial Positions

  • Medical Research Council (MRC) – Experimental Medicine Board
  • Associate Editor for Inflammation

Sources of Funding

More information on funding at Gwo-Tzer Ho's Research Explorer profile.

 

If you are interested in supporting our work by direct involvement, or funding our work on a charitable basis, please contact emma.watson@ed.ac.uk