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Professor Marcela Votruba

Professor Marcela Votruba

Professor and Hon. Consultant in Ophthalmology

School of Optometry and Vision Sciences

Email
votrubam@cardiff.ac.uk
Telephone
+44(0)29 2087 0117
Fax:
+44 (0)29 2087 4859
Campuses
Room 2.30, Optometry and Vision Sciences, Maindy Road, Cathays, Cardiff, CF24 4HQ
Comment
Media commentator
Users
Available for postgraduate supervision

Overview

Summary

The Mitochondria & Vision Research Group (M Votruba Lab) is interested in the role of mitochondrial dysfunction due to mutation in an expanding number of genes, in the pathophysiology of inherited optic neuropathy. Our approach has placed an emphasis on generating model systems to study retinal ganglion cell (RGC) loss and inner retinal degeneration. The current direction is to explore and evaluate novel therapeutic interventions.

My research spans two themes- Neuroscience and Ageing (https://www.cardiff.ac.uk/optometry-vision-sciences/research/themes/neurodegeneration-and-ageing)  and Stem cells, Regeneration and Repair (https://www.cardiff.ac.uk/optometry-vision-sciences/research/themes/stem-cells,-regeneration-and-repair).

It is embedded in two multi-disciplinary research groups- Neurodegeneration to Regeneration (https://www.cardiff.ac.uk/research/explore/research-units/n2r) and Ocular Therapeutics (https://www.cardiff.ac.uk/research/explore/research-units/ocular-therapeutics).

As part of my role as a Clinician Scientist, I also manage patients at the University Hospital Wales Eye Department with inherited eye diseases  such as inherited retinal dystrophiews and optic neuropahties, running a Retinal Clinic and a Genetic Eye Clinic, at the University Hospital of Wales. I also take part in both commercial and academic clinical research and trials.

Previously I have served as Head of School of Optometry & Vision Sciences for 6 years) (2014-2019).

Research overview

My goals are aimed at developing a deeper understanding of inherited eye disease and ultimately utilising my position as a clinical ophthalmologist to drive the application of translational research in this area. My primary research interest is the pathophysiology of hereditary retinal and optic nerve diseases. I am currently investigating inherited optic neuropathies, which are a pure model of isolated retinal ganglion cell loss. They demonstrate a central role for mitochondria and show some progressive neurodegeneration. Retinal ganglion cells are the cells that make up the nerve of vision, taking impulses from the retina to the brain. Autosomal dominant optic atrophy is the commonest inherited optic neuropathy. It is caused by mutations in the OPA1 gene, leading to visual loss, which first starts in children and young people. Clinical understanding of the disease is poor, although we have clinical and some pathological evidence that retinal ganglion cells are deficient in the eyes of patients. There is no treatment available. Conventional clinical or research strategies have yet to make any clinical impact on this state of affairs. The mechanism of action of the mutant protein OPA1 is not known, but clues exist suggesting that the shape or function of small organelles in the cell, mitochondria, may be involved. Mitochondria are important in generating energy in the cell. Following on from our work to characterise the disease phenotype and clone the disease gene, my group has analysed the spectrum of mutations in the OPA1 gene and genotype/ phenotype correlations. We have performed functional and expression studies of the OPA1 gene and assessed its wider role in inherited optic neuropathy and we are developing model systems to explore the mechanisms and pathways of RGC loss and exploring and testing novel therapies.

Biography

I am a clinically qualified and clinically active Professor of Ophthalmology at Cardiff University School of Optometry & Vision Sciences and an Honorary Consultant Ophthalmologist at the University Hospital of Wales, Cardiff.

I was awarded a Personal Chair at Cardiff University in 2011, having been Senior Lecturer there since 2003. I came to Cardiff from UCL with a Clinician Scientist Fellowship from the MRC, to fund myself and a research associate for four years.  Prior to this I was a Consultant in Medical Retina, at Moorfields Eye Hospital, London, UK in 2003 and a Visiting Researcher, at the National Eye Institute, National Institutes of Health, USA, in 2002. I was a fellow to Professor Paul Sieving, in 2002- first in Michigan, Ann Arbor at the Kellogg Eye Centre, and then at the National Eye Institute, National Institutes of Health, Bethesda. I completed my specialty and supra-specialty training in ophthalmology and ophthalmic genetics in 2000 and was awarded my certificate of completion of training. I was a clinical fellow under the guidance of Professors Tony Moore and Alan Bird and trained in medical retina and genetics at a world-leading centre. My fellowship of the Royal College of Ophthalmology (FRCOphth) was awarded in 1992. I studied Physiological Sciences at The Queen’s College, Oxford (BA, MA Hons 2:1, 1984/ 1987), where I was awarded an Open Scholarship in 1981. My Medical degree was at Green College, Oxford (BM BCh, 1987).

Honours and awards

Distinguished Fellowships

Elected Fellow of the Learned Society of Wales in 2017

Research Fellowships

1994                                   Guide Dogs for the Blind Association Research Fellowship

1998                                   Wellcome Trust Vision Research Training Fellowship

2002                                   Frost Research Fellowship

2003                                   MRC Clinician Scientist Fellowship

Postgraduate Prizes                   

1996                                  The Royal Society of Medicine: Ophthalmology Section-Registrars’ Meeting: First Prize (Awarded for the Best Paper at Annual Training Meeting)

Undergraduate Distinctions                  

1981                                   Open Scholarship, The Queen’s College, Oxford

1984                                   First Class Hons. Dissertation, Oxford University

1987                                   Final Year Clinical Prize: Green College, Green College, Oxford

 

 

Professional memberships

Memberships, Affiliations and Societies

European Vision Institute (EVI)

European Paediatric Ophthalmology Society (EPOS)

British Eye Study Group (BESG)

UK Eye Genetics Group (UK EGG)

European Retina, Macula and Vitreous Society (EuroRetina)

Association for Research in Vision & Ophthalmology (ARV0)

International Society of Eye Research (ISER)

European Association for Vision & Eye Research (EVER)

European Society Human Genetics (ESHG)

The Oxford Ophthalmological Congress (OOC)

International Society for Genetic Eye Disease (ISGED)

Academic positions

Present Substantive Appointment

Professor of Ophthalmology, Cardiff University  and Consultant in Ophthalmology, Cardiff & Vale NHS Trust, University Hospital Wales

Previous Substantive Appointments

Jan 2014- Dec 2019                 Head of School of Optometry & Vision Sciences, Cardiff University

Aug 2011 - Dec 2013                Professor and Honorary Consultant in Ophthalmology, Cardiff University and The Cardiff & Vale    NHS Trust, University Hospital of Wales

Oct 2007  - July 2011                Honorary Consultant Senior Lecturer, Cardiff University and The Cardiff & Vale NHS Trust, University Hospital of Wales.

Oct 2003 - Sep 2007                  MRC Clinician Scientist Fellow & Honorary Consultant Senior Lecturer, Cardiff University and The University Hospital of Wales

 Apr 2003 - Oct 2003                   Consultant in Medical Retina, Moorfields Eye Hospital, London & Service Lead for Audit & Clinical Governance & Service Lead for ARMD Research

Other Appointments

2019                                         Visiting Professor, Charles University Prague, Czech Republic

2002                                         Visiting Research Scholar, National Eye Institute, National Institutes of Health, Bethesda, MD, USA

Speaking engagements

Invited plenary or keynote lectures at major conferences

  • 2016 European Vision & Eye Research Keynote Lecture: Mitochondrial optic neuropathies- new therapies in sight (all expenses paid)

Recent Invited Lectures

 2019

  • Speaker, Chair and Organiser Royal Society of Medicine Symposium on Mitochondrial Eye Disease, Jan 2019 (all expenses paid)
  • Royal College of Ophthalmologists Annual Congress, SIS Speaker, May 2019
  • Oxford Medical School Mitochondrial research group inviyed speaker (Nov 2019)
  • Optic Nerve Meeting, Obergurgl, speaker, Dec 2019

2018

  • Royal College of Ophthalmologists Annual Congress, SIS Speaker
  • EVER 2018. SIS Mitochondrial eye disease. Co-Chair. Oct 2018
  • South West Ophthalmological Society 2018. Invited Speaker, Nov 2018
  • Prague LHON Expert Forum, Invited Speaker and Chair, Dec 2018 (all expenses paid)
  • Japan Exchange, speaker Dec 2018 (all expenses paid)

2017

  • MRC Mary Lyons Centre, Harwell, Oxfordshire, March 2017 (all expenses paid).
  • ARVO 2017: Special Interest Symposium Co-Chair, Mitochondrial optic neuropathies, May 2017.
  • The Royal College of Ophthalmologists Annual Congress - invited speaker at SIS Neurodegeneration & the Eye, May 2017, Liverpool.
  • Barcelona, EUPON Invited Speaker, March 2017 (all expenses paid).
  • EVER 2017. SIS Mitochondrial eye disease. Co-Chair. Oct 2017

2016

  • European Optic Nerve Meeting, Milan, Italy (all expenses paid)
  • Cambridge Ophthalmological Symposium, Cambridge (all expenses paid)
  • Welsh School of Pharmacy Seminar: Mitochondrial optic neuropathy- pathophysiological insights and novel therapeutic interventions
  • EVER Keynote Lecture: Mitochondrial optic neuropathies- new therapies in sight. (all expenses paid)

Invited Faculty

2018    Expert Panel Mitochonrial optic neuropathies, Santhera, Prague

2013    European Neuromuscular Consortium, Naarden, Holland

2012    European Professors of Ophthalmology, Leuven, Belgium

2009    Keystone Symposium: Mitochondrial Dynamics and Physiology, Whistler, Canada

2008    Great Ormond Street Hospital/ Moorfields Paediatric Ophthalmology Course

2007    Great Ormond Street Hospital/ Moorfields Paediatric Ophthalmology Course

2006    Great Ormond Street Hospital/ Moorfields Paediatric Ophthalmology Course

2004    The European University Professors in Ophthalmology (EUPO), Nijmegen

2003    The Cambridge Ophthalmological Symposium, Cambridge

2001    The Electrophysiology of Vision Course, Moorfields Eye Hospital, London

Committees and reviewing

Grant advisory panels

  • 2020-2025  Deputy Chair, Fight for Sight Grant Advisory Panel, UK
  • 2015 – 2020 Member Grant Advisor Panel, National Eye Research Centre, UK
  • 2017– 2020 Member Grant Advisory Board, RP Fighting Blindness/ Retina UK
  • 2012 – 2017 Member Grant Advisory Panel, Fight for Sight, UK

Leadership roles in learned societies or professional bodies

  • 2019-2024 Secretary General, European Association for Vision and Eye Research.
  • 2019-2024 Representative for European Association for Vision & Eye Research on EU-EYE Board.
  • 2018- 2020 Invited Member of the James Lind Alliance Priority Setting Partnership Steering Board: “Rare Mitochondrial Diseases”.
  • 2016 - 2018 National Ophthalmology Specialty Lead for Wales.
  • 2016 - 2018 Member of the UK Specialty Lead Panel for Ophthalmology Trials.
  • 2014 - 2017 Member of the VISION 2020 UK Eye Research Committee.
  • 2012- 2014 Lead Principal Investigator and Co-ordinator of the MRC Mouse Eyes & Vision Consortium.
  • 2012 - 2017 Member Steering Committee, UK Eye Genetics Group.
  • 2012 - 2013 Royal College of Ophthalmologists Representative on James Lind Alliance Priority Setting Partnership Steering Committee: “Sight Loss and Vision”.
  • 2013   Invited Faculty Member, European Neuromuscular Consortium, Naarden, Holland.
  • 2011 - 2016 Programme Secretary, European Association for Vision and Eye Research.
  • 2009 - 2010 Vice President, European Association for Vision and Eye Research.
  • 2004 - 2009 Section Chair for Molecular Biology/ Genetics/ Epidemiology, Board of European Association for Vision and Eye Research (EVER).

Editorships of journals

  • 2013- present: Associate Editor, Editorial Board of Acta Ophthalmologica,
  • 2020- present: Associate Editor Therapeutic Advances in Rare Disease

 Guest editorships of books or special editions of journals

  • 2013 Guest Editor for Drug Discovery Today: Disease Models

 Other examples of leadership in the academic community

  • 2008 & 2011 Jury member, Belgian Ophthalmology Research Prize.
  • 2004 & 2009 Jury member, College of Ophthalmologists Research Prize.

Leadership roles in industry

  • Expert Panel Member, Novartis Gene Therapy for RPE65 Leber’s congential amaurosis, London 2018
  • Expert Panel Member, Chair and Invited Speaker at Mitochonrial optic neuropathies“, Santhera Pharmaceuticals, Prague, 2019

Review of papers for scientific journals

I regularly review papers for scientific journals, including ophthalmology and neuroscience journals- Brain, Investigative Ophthalmology & Vision Science, Archives of Ophthalmology, The British Journal of Ophthalmology, Eye, Ophthalmic Research, Neuro-ophthalmology, Acta Ophthalmologica and Experimental Eye Research and genetics journals- Human Molecular Genetics, American Journal of Human Genetics, Journal of Medical Genetics, Human Genetics, European Journal of Human Genetics and Ophthalmic Genetics.

I also regularly review Grant Applications for national bodies- The MRC, The Wellcome Trust, Fight for Sight, The Macular Disease Society, The Guide Dogs for the Blind Association, The Iris Fund, the National Eye Research Center and international bodies, including, the Swiss National Science Foundation and Association Francaise contre les Myopathies.

Publications

2021

2020

2019

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2016

2015

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1999

1998

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1994

1993

Teaching

Undergraduate Optometry Teaching

I lecture and examine final year optometry students on abnormal ocular conditions  and case based learning.

Postgraduate Teaching in Ophthalmology

I participate in postgraduate teaching in ophthalmology at the University Hospital, Wales.

Research Interests

My research focus is on the role of mitochondria in the pathophysiology of neurodegenerative disease. My focus has been inherited optic neuropathy, with an emphasis on generating model systems to study retinal ganglion cell (RGC) loss and inner retinal degeneration, which occurs as a primary phenomenon in a number of human genetic diseases.

We are studying RGC loss and rescue in vitro and in vivo, and the sequelae of this neurodegeneration on inner retina. To this end, we have been utilising retinal ganglion cell lines and primary RGCs, to explore the effect of mitochondrial fusion and fission genes on cell viability and the mechanism of cell death. We are also exploring the role of neuroprotective agents. OPA1 is known to bind to the inner mitochondrial membrane, and when mutated it is believed that the normal balance of mitochondrial fusion and fission is disturbed and programmed cell death is initiated by the loss of mitochondrial membrane potential and the release of cytochrome c. We are also investigating the role of the OPA3 gene in both RGC loss and cataract formation. OPA3, like OPA1, is thought to have a role in mitochondrial membrane dynamics, and when mutated in the human, a complex neurodegenerative disease, comprising optic neuropathy secondary to RGC loss, cataract and neuromuscular degeneration, arises.

Current Research Team

  • Dr Dinesh Kumar Kandaswamy, Newton International Fellow
  • Dr Matthieu Trigano
  • Dr Thomas Freeman

Current Postgraduate Research Students

  • Shanshan Sun
  • Gloria Cimaglia

Research Alumni

Post- doctoral Research Associates

  • Dr Vanessa Davies
  • Dr Ruby Grewel
  • Dr Andrew Hollins
  • Dr Kate Powell
  • Dr Terry Smith
  • Dr Kathy Beirne
  • Dr Carmine Varrachio
  • Dr Irina Erchova

Technical Assistants

  • Elaine Taylor
  • Sharon Seto
  • Pascale Aeschlimann

Former PhD Students

  • Dr Jack Sheppard
  • Dr Gosia Piechota
  • Dr Jennifer Davies
  • Professor Pete Williams
  • Dr Carolyn Walker
  • Dr Kathy Beirne
  • Dr Carmine Varricchio

Professional Training Scheme

  • Rebecca Thirgood

EVER Foundation Fellows

  • Dr Pratyusha Ganne BM BCh FRCOphth
  • Dr Deepti Mahajan  MD FRCOphth

Summer Students

Dr Marrios Sarros MD, Dr Costas Karabatsas MD, Yip Wan Fen NSc, Laura Byrne, Amanda Mui, Rebecca Watts, Roshini Joseph, Oliver Coppleston, Christopher Man, Kestutis Satkus

Current grant funding

 2019-2021                Academy of Medical Sciences Newton International Fellowship. Host  M Votruba. Fellow Dr Dinesh Kumar Kandaswamy. “Near-infrared light therapy as a therapeutic regimen for inherited optic neuropathy.”

2019-2022                   Fight for Sight Studentship. Morgan JE, Votruba M, Williams P. “NAD therapy in glaucoma”.

2019-2020                  Wellcome Trust ISSF3 Consolidator Award. C Varrachio. M Votruba, Sponsor Dr B Newlands. 

2019-2020                  Wellcome Trust ISSF3 Cross Disciplinary Award. Light for Sight – neuroprotection in mitochondrial optic neuropathy. M Votruba, M Rozanowska, J Hicks, S Armstrong. 

2020-2021                  National Eye Research Centre Project Grant. “Sustained release formulations for new drugs in the treatment of mitochondrial optic neuropathies.”  Votruba M, Brancale A, Rozanowska M and Heard C.

Research Collaborators

International

Professor Anne A. Knowlton, M.D., Professor of Medicine and Medical Pharmacology, Molecular & Cellular Cardiology, University of California, Davis, California, USA.

Professor Don Newmeyer, PhD, La Jolla Institute for Allergy and Immunology, La Jolla, CA , USA.

Professor Peter Nuernberg, PhD, Cologne Centre for Genomics, University of Cologne, Germany.

Professor Sayan Roy, Ph.D., FARVO, Professor of Medicine, Section of Diabetes, Endocrinology & Nutrition  & Professor of Ophthalmology, Boston University School of Medicine, USA. 

Professor Pete Williams, Assistant Professor, Dept. of Clinical Neuroscience, Section of Ophthalmology and Vision, Karolinska Institute, Stockholm

National

Dr Patrick Yu-Wai-Man, MRC Clinician Scientist, Mitochondrial Research Group, The Medical School ¨University of Cambridge and UCL, Moorfields Eye Hospital

Professor Ron Douglas, Professor of Visual Science: Deputy Head of Department, City University London

Professor Jo Poulton, PhD MRCP, Professor of Mitochondrial Genetics, John Radcliffe Hospital, University of Oxford

Professor Tim Wells, PhD, School of Bioscience, Cardiff University.

Professor Andrea Brancale PhD and Dr Charles Heard PhD, Welsh School of Pharmacy and Pharmaceutical Sciences, Cardiff University

Supervision

Current students

2019-2022

Fight for Sight Studentship Gloria Cimaglia, co-supervisor with James Morgan and Pete Williams. Title: “NAD in glaucoma neuroprotection”.

2017-2020

Chinese Scholarship Council/ Vice Chancellor’s Scholarship. Shanshan Sun. Primary Supervisor. Co-supervised with Prof Frank Sengpiel and Dr Irina Erchova.  Title: “Mitochondrial dynamics in neurodegeneration.”

I am interested in supervising PhD students in the areas of:

  • Role of mitochondria in neurodegeneration
  • Novel therapies for mitochondrial optic neuropathies
  • iPS cells for the testing of novel therapy of mitochondrial dysfunction
  • Mitochondrial damage in age related macular degeneration
  • Quality of life in patients with inherited retinal and optic nerve disease, utility of novel therapies

Current supervision

Gloria Cimaglia

Research student

Past projects

2016-2019

NRN Joint Cardiff School of Pharmacy and School of Optometry & Vision Sciences Studentship. Carmine Varricchio. Primary Supervisor. Co-Supervised with Prof Andrea Branca, Dr Charles Heard and Dr Malgorzata Rozanowska. Title: “Intelligent drug design in mitochondrial optic neuropathy:”

2014-2017

College of Optometry Studentship. Rupal Shah. Second co-supervisor, with Prof Jez Guggenheim. Title: “Discovery of genetic determinants for refractive error.”

2013-2016

Fight for Sight Studentship. Kathy Beirne. Primary Supervisor. Co-Supervised with Prof J Morgan & Dr M Rozanowska. Title: "Light therapy for mitochondrial optic neuropathy".

2013-2015

Ghanean Education & Training Fund: Enyam Mornay. Primary Supervisor. Co-Supervised with Dr Tom Margrain. Title: “Biomarkers of early disease and progression in inherited optic neuropathy”.

2011-2013

BBSRC Studentship: Caroline Walters. Primary Supervisor. Co-Supervised with Dr Malgorzata Rozanowska. Title: “Therapeutic rescue of Opa1 mutants”.

2009-2012

MRC Studentship: Peter Williams. Primary Supervisor. Co-Supervised with Professor James Morgan. Title: “Role of OPA1 in retinal ganglion cell dendritic remodeling.”

2006-2009

MRC/ BBSRC Studentship: Jennifer Davies. Primary Supervisor. Co-Supervised with Dr Andrew Quantock. Title: “Structure and function of the opa3 protein: disease mechanisms at the inner mitochondrial membrane.”

2005-2008

School Vision Sciences Studentship: Malgorzata Piechota. Primary Supervisor. Co-Supervised with Prof. Mike Boulton. Title: "Investigating the pathophysiology of inherited optic atrophy: the phenotypic characterisation of novel murine targeted opa1 and opa3 mutants, functional studies and novel rescue strategies".

2004-2007

MRC Studentship: Jack Sheppard. Primary Supervisor. Co-Supervised with Prof. Keith Meek. Title: "Genetic and structural pathogenesis of keratoconus: the role of the VSX1 gene".