Prinicipal Investigator

Molecular mechanisms driving age-related macular degeneration

Home » Labs » Clark Lab » Members » Simon Clark

Simon Clark

Surname Clark
First name Simon
Nationality British
Present position and title Helmut Ecker Endowed Professor in AMD

Business address

Institute for Ophthalmic Research
University of Tübingen
Elfriede-Aulhorn-Strasse 7
D-72076 Tübingen,
Germany

Phone: +49 (0)7071 29-87894
E-mail: simon.clark[at]uni-tuebingen.de

Academic Education

Year Degree University Field of study
2007 D.Phil. University of Oxford Biochemistry
2002 B.Sc.(hons) University of Aberdeen Biochemistry (with Immunology)

Professional Experience

Period Institution Position Discipline
Current University of Tübingen Research Professor Molecular mechanisms of AMD
Current University of Manchester Honorary Professor Biochemistry/Complement Biology
09/2018 – 10/2019 University of Manchester Research Fellow Biochemistry/Complement Biology
09/2013 - 08/2018 University of Manchester MRC Intermediate Fellow Biochemistry/Complement Biology
01/2012 - 08/2013 University of Manchester Stepping Stones Fellow Biochemistry/Complement Biology
10/2006 - 12/2011 University of Manchester Post-Doc Biochemistry/Complement Biology

Professional Activities and Functions

Invited Presentations

15th Feb. 2019 University of Liverpool, Dept. of Eye and Vision Science, Liverpool, UK: Molecular mechanisms driving Age-related Macular Degeneration: understanding the role of complement.
26th Nov. 2018 University of Tübingen Faculty of Medicine, Tübingen, Germany: Molecular Mechanisms behind AMD.
11th Sept. 2018 International Society for Eye Research, Belfast, NI: RPE-Choroid Pathological immune processes.
31st May 2018 University of Copenhagen Graduate School of Immunology: Understanding complement dysregulation in AMD pathogenesis: implications for new therapeutic avenues.
4th Sept. 2017 Eye Development and Degeneration: From Genes to Therapy conference, MRC Human Genetics Unit, University of Edinburgh: Factor H-related proteins in AMD pathogenesis.
20th Oct. 2015 Institute of Genetic Medicine, University of Newcastle: A tale of two post-codes: GAG mediated regulation of innate immunity in both eyes and kidneys.
6th-9th Aug. 2015 World Congress on Ocular Cell and Regenerative Biology, Guangzhou, China: Contribution of complement proteins to immune homeostasis on Bruch’s membrane and the choriocapillaris.
30th April 2015 Radboud Institute for Molecular Life Sciences, Nijmegen Medical Centre, Radboud University, The Netherlands: Biochemical mechanisms underlying age-related macular degeneration.
7th Nov. 2013 John Humphrey Lecture series, Imperial College London, London, UK: Innate immune regulation and the development of Age-related Macular Degeneration.

Organization of Academic Events

26th-27th March 2018 National conference – Complement UK, Manchester, UK.

Academic Awards

Sept. 2018 Macular Society Annual Awards for Excellence, Rising Star Award, awarded at the national meeting, London.
Sept. 2013 MRC Career Development Fellowship, competitive independent fellowship
Sept. 2012 Stepping Stones Junior Fellowship, competitive independent fellowship

Academic Services

  • International External PhD examiner

    • Ms. Maartje Geerlings ‘Studies of rare genetic variants in age-related macular degeneration’ Radboud University Medical Centre, The Netherlands, 15th February 2018.
    • Mr. Carsten Faber ‘Age-related macular degeneration and systemic inflammation’, Pannum Institute, University of Copenhagen, Denmark, 13th June 2013.

  • National External PhD examiner

    • Ms. Orla McMahon, ‘The role of the P167S C9 rare genetic variant in the pathogenesis of age-related macular degeneration’ Newcastle University, UK, 23rd Sept. 2019.
    • Mr. Homam Ageel, ‘Characterisation of the interaction between the complement system and the bacteria Neisseria meningitidis’. University of Leicester, UK, 5th June 2018.
    • Mr. Hussein Mohammad Abbow, ‘Studies on ligand interactions of human complement factor H’ University of Leicester, UK, 24th March 2017.
    • Dr. Edwin Kwan Soon Wong, ‘Complement abnormalities in Membranoproliferative Glomerulonephritis and C3 Glomerulopathy’, Newcastle University, UK, 16th May 2016.
    • Ms. Hanan Alrashidi ‘The interplay of complement proteins C1q and factor H’, University of Leicester, UK, 18th December 2015.

  • External tutorials

    • ‘Complement and eye disease’, Complement UK national symposium and teaching day, College Court, Leicester, 24th-25th Nov 2016.
    •  ‘Complement and Chronic Inflammation’, Complement UK national symposium and teaching day, Christ’s college, Cambridge, 23rd-24th March 2015.

Memberships

  • Elected to member and Treasurer of the European Complement Network board, the International organisation responsible for the promotion and co-ordination of complement research across Europe, since 2019
  • Editorial Board member Scientific Reports since 2019.
  • Member of the Translational Ophthalmology Steering Committee for University of Manchester Intellectual Property services (UMIP), defining UMIPs translational strategy in the eye care sector
  • Guest Editor for a special issue of the journal Immunobiology, 2018
  • Member of the executive committee for Complement UK, the national organisation responsible for the promotion, education and translation of complement research in the UK, 2017 – Present.
  • Invited to participate in the Action Against AMD retreat, Wellcome Genome Campus, Hinxton, 5th – 6th June 2017, where 40 leading experts from around the World were asked to identify research and funding priorities, and define strategies to promote the development and delivery of treatments for AMD.
  • Academic Editor on Editorial Board for PLoS one since 2016
  • Review Editor on Editorial Board for Frontiers in Immunology (Molecular Innate Immunity section) since 2015
  • Member of the Macular Society’s Professional Advisory Panel, since 2016.

Past and Current Funding

Career total to date (revenue, excluding FeC) = £3,121,392

09/2019 – 08/2022
Current
Fight for Sight PhD Studentship (2033), £98,768: Investigating the role of Inter-Alpha-Inhibitor Heavy Chain 3 in age-related macular degeneration. Lead applicant.
09/2018 – 08/2021
Current
Macular Society, £164,042: A comprehensive molecular analysis and iPSC model of early adult-onset macular degeneration to better understand age-related macular degeneration. Co-applicant.
12/2017 – 12/2020
Current
Macular Society, £169,318: Development and utilisation of Manchester Eye Tissue Repository to elucidate molecular pathology of AMD. Co-applicant.
07/2018 –04/2019 MRC Confidence in Concept award, £73,825: Development of a novel treatment for age-related macular degeneration. Co-applicant.
09/2017 – 06/2018 MRC Confidence in Concept award, £52,315: Optimisation of a novel chimeric protein to promote its cell secretion for the treatment of age-related macular degeneration by gene therapy. Lead applicant.
05/2017 – 04/2020
Current
Medical Research Council (MR/P025838/1), £492,648: Investigating the Influence of Genetic Variation Associated with Age-Related Macular Degeneration on Plasma Levels of Compliment Regulatory Proteins. Co-applicant.
09/2016 – 08/2018 Fight for Sight, (1852/53), £110,257: Influence of factor H and factor H-like protein 1 on retinal pigment epithelial cell interactions with Bruch’s membrane. Sole applicant.
11/2014 – 09/2015 Fight for Sight, (24NE141), £14,547: Investigating epigenetic modifications in the etiology of age-related macular degeneration. Lead applicant.
09/2014 – 08/2017 Macular Society, £166,602: Establishment of a national eye tissue archive for age-related macular degeneration research. Co-applicant.
09/2014 – 08/2017 Fight for Sight, (1517/18), £169,809: Elucidation of molecular mechanisms underpinning disease initiation and progression in are-related macular degeneration. Co-applicant.
09/2013 – 09/2018 Medical Research Council Career Development Award (MR/K024418/1), £664,960: Investigating the role of complement factor H-like protein-1 and factor H related proteins in age-related macular degeneration. Sole applicant.
10/2012 – 09/2015 Medical Research Council (MR/K004441/1), £480,344: Investigating age-dependent regulation of complement in human eye tissues: implications for Age-related Macular Degeneration. Co-applicant.
01/2012 – 12/2014 Stepping Stones Research Fellowship, FMHS, University of Manchester, £85,502: Investigation into the role of factor H-like protein 1 (FHL-1) in age-related macular degeneration. Sole applicant.
10/2009 – 09/2012 Medical Research Council (G0900592), £409,442: Host tissue recognition by complement factor H in the human eye: mapping changes with age and in AMD. Co-applicant.
10/2008 – 09/2009 Macular Disease Society, £42,838: Towards therapeutics for AMD: functional and structural characteristics of complement factor H Y402H polymorphism. Co-applicant.

Selected Publications

* = joint first author, and § = corresponding author.

  1. Cipriani, V., Lores-Motta, L., He, F., Fathalla, D., Tilakaratna, V., McHarg, S., Bayatti, N., Acar, I.E., Hoyng, C.B., Fauser, S., Moore, A.T., Yates, J.R.W., International Age-related Macular Degeneration Genomics Consortium (IAMDGC), Morgan, B.P., de Jong, E.K., den Hollander, A.I., Bishop, P.N and §Clark, S.J. (2020) Factor H-related protein 4 drives complement activation in age-related macular degeneration. (Nature Commun. 11, 778)
  2. Taylor, R.L., Poulter, J.A., Downes, S.M., McKibbin, M., Khan, K.N., Inglehearn, C.F., Webster, A., Hardcastle, A.J., Michaelides, M., Bishop, P.N., Clark, S.J. and Black, G.C. (2019) Deleterious mutations in the CFH gene affecting alternatively encoded Factor H-like 1 protein cause early onset macular degeneration. Ophthalmol. 126, 1410-1421.
  3. Swinkels, M., Zhang, J., Tilakaratna, V., Bishop, P.N., Black, G., Perveen, R., McHarg, S., Day, A.J. and §Clark, S.J. (2018) C-reactive protein binding properties of factor H-like protein 1 differ from complement factor H: implications for inflammation in the eye. Sci. Rep. 8, 1643.
  4. §Clark, S.J., McHarg, S., Tilakaratna, V. Brace, N, and Bishop, P.N. (2017) Bruch’s membrane permeability maintains two immunologically independent sites in the eye: implications for treating age-related macular degeneration. Front. Immunol. 8, 1778.
  5. Black, J.R.M. and §Clark, S.J. (2016) Age-related macular degeneration: GWAS to translation. Genet. Med. 18, 283-289.
  6. McHarg, S., Brace, N., Bishop, P.N. and §Clark, S.J. (2015) Enrichment of Bruch’s membrane from human donor eyes. J. Vis. Exp. 105, e53382.
  7. §Clark, S.J., Schmidt, C.Q., White, A.M., Hakobyan, S., Morgan, B.P. and Bishop, P.N. (2014) Identification of factor H-like protein 1 as the predominant complement regulator on Bruch’s membrane: implications for age-related macular degeneration. J. Immunol. 193, 4962-4970.
  8. Clark, S.J., Ridge, L.A., Hakobyan, S., Uhrin, D., Morgan, B.P., Lennon, R., Würzner R., Bishop, P.N. and Day A.J. (2013) The two heparin-binding domains in complement factor H show differential contributions to binding site recognition in human eyes and kidneys. J. Immunol. 190, 2049–2057.
  9. *Clark, S.J., *Keenan, T.D.L., Fielder, H.L., Collinson, L.J., Holley, R.J., Merry, C.L., van Kuppevelt, T.H., Day, A.J. and Bishop, P.N. (2011) Mapping the differential distribution of glycosaminoglycans in the adult human retina, choroid and sclera. Invest. Ophthalmol. Vis. Sci. 52, 6511-6521.
  10. Clark, S.J., Perveen, R., Hakobyan, S., Morgan, B.P., Sim, R.B., Bishop, P.N. and Day, A.J. (2010) Impaired binding of the AMD-associated complement factor H 402H allotype to Bruch’s membrane in human retina. J. Biol. Chem. 285, 30192-30202.
  11. Clark, S.J., Higman, V.A., Mulloy, B., Perkins, S.J., Lea, S.M., Sim, R.B. and Day, A.J.  (2006) H384 allotypic variant of factor H associated with age-related macular degeneration has different heparin-binding properties from the non-disease-associated form. J. Biol. Chem. 281, 24713-24720.

Additional information

Patents

  • Methods for assessing and treating complement-related disorders (PCT/EP19/062048). Filed 10/05/2018. Simon J Clark & Paul N. Bishop
  • C3b Binding Polypeptide (WO/2019/138137). Filed 15/01/2018. Simon J. Clark, Richard Unwin & Paul N. Bishop.
  • C3b Inactivating Polypeptide (WO/2018/224663). Filed 09/06/2017. Simon J. Clark, Richard Unwin & Paul N. Bishop.
  • Screening assays for binding antagonists of the AMD-associated variant of factor H (H384).  US Patent (No. US7829301B2). Filed 07/2007, granted 11/2010.  Anthony J. Day, Simon J. Clark, Paul N. Bishop, Robert B. Sim, Anna Blom & Dick Heinegård co-inventors.