Fibrosis Research Group
While fibrosis is the causative pathology of more than 40% of mortality in the Western world, the treatment options are limited in numbers and efficacy. View the video below to find out more about fibrosis.
Our group focuses on discovery and development of novel anti-fibrotic drugs through phenotypic screening assays rather than single-target approach. We develop and validate in vitro and in vivo phenotypic screening assays that are relevant to pathophysiology of fibrosis. Our in vitro cell models are based on human primary cells, rather than commercially available cell lines.
We have developed and validated phenotypic assays amenable to high throughput screening, as well as secondary functional assays. One of our workstreams has identified two hit compounds which have been further tested and validated in in vivo models and have been shown to be efficacious in clinical studies.
Our group is developing several phenotypic assays in growing number of fibrotic diseases, as shown in the pipeline below:
Above: Diagram showing our current progress. We're at the clinical development stage for Peyronie's disease; hit validation stage for hypertrophic scarring; phenotypic assay development stage for pulmonary fibrosis, intra-abdominal adhesions, cardiac fibrosis, and lymphangioleiomyomatosis (LAM); and human tissue acquisition stage for liver fibrosis.
We offer our in vitro cellular phenotypic assays to external groups and organisations; we will be happy to test your lead/candidate compounds/molecules. We are also open to discussion around development of novel phenotypic assays for fibrosis or other indications with unmet need.
Please contact [email protected] for more information.
Researchers
- Prof Selim Cellek - Professor of Health and Biomedicine (group lead)
- Dr Alice Lapthorn - Research Fellow
- Kieran Feltham - Research Assistant
- Dr Sophie Harding - Research Assistant
Current doctoral students
- Matthew Megson
- Isuru Perera
Past doctoral students
- William Stebbeds (LifeArc)
- Marta Mateus (Charles River)
- Marcus Ilg (ExoBio)
Collaborators
- Prof David J. Ralph (University College London)
- Prof Peter D. Dziewulski (St Andrew’s Centre for Plastic Surgery and Burns)
- Prof Jim Khan (Portsmouth University)
- Dr Dave Smith (AstraZeneca)
- Mr Alberto Albanese (Essex Cardiothoracic Centre)
- Mr Tariq Minhas (Essex Cardiothoracic Centre)
- Prof Simon Johnson and Dr Debbie Clements (University of Nottingham)
- Dr Felicity de Cogan (University of Nottingham)
Funders
- European Society for Sexual Medicine
- GUTS UK
- British Skin Foundation
- Biochemical Society
- British Dupuytren Society
- Peterborough Burns Unit Appeal Fund
Recent activity
Dr Alice Lapthorn and Kieran Feltham presented their research at the British Society of Investigative Dermatology Annual Meeting from 15-16 April 2024 in Southampton.
Prof Selim Cellek, Dr Marcus Ilg and Dr Sophie Harding presented their research and chaired sessions at the European Society for Sexual Medicine (ESSM) Annual Congress from 8-10 February 2024 in Bari, Italy. Sophie won the Best Podium Presentation in Basic Science award for her talk titled "Phosphodiesterase type 5 inhibitors prevent myofibroblast transformation in Peyronie’s disease through the cAMP/PKA pathway, potentially through PDE1/PDE4".
Dr Marcus Ilg's article, 'Time heals all wounds, but what if the healing never stops? An exploration of drug discovery in fibrosis', was chosen as a runner-up in the 2023 Early Career Pharmacology writing competition, which challenged researchers to explain a complex subject to a wide audience. His article is now live on the Pharmacology Matters website, and free for all to read and share.
Dr Alice Lapthorn was shortlisted as a finalist for this year’s STEM for Britain competition.
On 6 March 2023, she presented her research to experts in her field and MPs at the House of Commons.
Her poster was titled “Hydroxypyridone anti-fungals as a novel therapeutic for hypertrophic scarring”.
Dr Marcus Ilg won the Best Basic Science Presentation Award at the 24th Annual Congress of the European Society for Sexual Medicine (ESSM) in Rotterdam, The Netherlands on 16-18 February 2023 with his presentation titled “Extracellular vesicles isolated from Peyronie’s disease-derived cells can alter TGF-beta 1 signalling cascades”.
Dr Marcus Ilg presented his research on the role of extracellular vesicles in Peyronie's disease at ISEV2022, which ran from 25-29 May in Lyon, France.
ISEV annual meetings are the world's largest and premier meeting on extracellular vesicles research, featuring the best in vesicle science while covering all aspects of fundamental, translational, and clinical research.
Dr Alice Lapthorn presented her research which investigated the anti-fibrotic effect of hydroxypyridone anti-fungals at the British Society for Investigative Dermatology Annual Meeting (Newcastle, UK, April 2022), where she won the award for Best Presentation by a Post-doctoral Scientist.
Right: Alice Lapthorn (far right) with three other delegates at the British Society for Investigative Dermatology Annual Meeting
Sophie Harding presented her research at Pharmacology 2022 @ Liverpool organised by The British Pharmacological Society on 13-14 September 2022.
Her abstract titled “Mechanism of Action of Phosphodiesterase Type 5 Inhibitors in Preventing Human Myofibroblast Transformation” was selected as one of the few Flash Poster presentations.
Selection of full papers
Ilg, M. M., Harding, S., Lapthorn, A. R., Kirvell, S., Ralph, D. J., Bustin, S. A., Ball, G. and Cellek, S. (2024) 'Temporal gene signature of myofibroblast transformation in Peyronie's disease: first insights into the molecular mechanisms of irreversibility', The Journal of Sexual Medicine, 21(4), pp. 278-287. Available at: https://doi.org/10.1093/jsxmed/qdae006
Lapthorn, A. R., Ilg, M. M., Dziewulski, P. and Cellek, S. (2024) 'Hydroxypyridone anti-fungals selectively induce myofibroblast apoptosis in an in vitro model of hypertrophic scars', European Journal of Pharmacology, 967, 176369. Available at: https://doi.org/10.1016/j.ejphar.2024.176369
Castiglione, F., Çakır, O. Ö., Schifano, N., Corona, G., Reisman, Y., Bettocchi, C., Cellek, S. and Ilg, M. M. (2023) 'European Society of Sexual Medicine consensus statement on the use of animal models for studying Peyronie's disease', Sexual Medicine, 11(4), qfad046. Available at: https://doi.org/10.1093/sexmed/qfad046
Cellek, S., Megson, M., Ilg, M. M. and Ralph, D. J. (2023) 'A combination of phosphodiesterase type 5 inhibitor and tamoxifen for acute Peyronie's disease: the first clinical signals', The Journal of Sexual Medicine, 20(8), pp. 1057-1059. Available at: https://doi.org/10.1093/jsxmed/qdad083
Ilg, M. M., Ralph, D. J. and Cellek, S. (2023) 'Statins synergize with phosphodiesterase type 5 inhibitors but not with selective estrogen receptor modulators to prevent myofibroblast transformation in an in vitro model of Peyronie's disease', The Journal of Sexual Medicine, qdad051. Advance online publication. Available at: https://doi.org/10.1093/jsxmed/qdad051
Ilg, M. M., Lapthorn, A. R., Ralph, D. J. and Cellek, S. (2022) 'Phenotypic screening of 1,953 FDA-approved drugs reveals 26 hits with potential for repurposing for Peyronie's disease', PLOS One, 17(12), e0277646. Available at: https://doi.org/10.1371/journal.pone.0277646
Lapthorn, A. R., Ilg, M. M., Sullivan, J. V., Dziewulski, P. and Cellek, S. (2022) 'Phenotypic screening identifies hydroxypyridone anti-fungals as novel medicines for the prevention of hypertrophic scars', European Journal of Pharmacology, 937, 175374. Available at: https://doi.org/10.1016/j.ejphar.2022.175374
Christiansen, L., Sanmartin Berglund, J., Anderberg, P., Cellek, S., Zhang, J., Lemmens, E., Garolera, M., Mayoral-Cleries, F. and Skär, L. (2021) 'Associations Between Mobile Health Technology use and Self-rated Quality of Life: A Cross-sectional Study on Older Adults with Cognitive Impairment', Gerontology & Geriatric Medicine, 7, 23337214211018924. Available at: https://doi.org/10.1177/23337214211018924
Milenkovic, U., Boeckx, B., Lambrechts, D., Janky, R., Hatzichristodoulou, G., van Renterghem, K., Gevaert, T., Cellek, S., Bivalacqua, T. J., De Ridder, D. and Albersen, M. (2022) 'Single-cell Transcriptomics Uncover a Novel Role of Myeloid Cells and T-lymphocytes in the Fibrotic Microenvironment in Peyronie's Disease', European Urology Focus, 8(3), pp. 814-828. Available at: https://doi.org/10.1016/j.euf.2021.04.012
Friebel, T. R., Narayan, N., Ramakrishnan, V., Morgan, M., Cellek, S. and Griffiths, M. (2021) 'Comparison of PEAK PlasmaBlade™ to conventional diathermy in abdominal-based free-flap breast reconstruction surgery - A single-centre double-blinded randomised controlled trial', Journal of plastic, reconstructive & aesthetic surgery: JPRAS, 74(8), pp. 1731-1742. Available at: https://doi.org/10.1016/j.bjps.2020.12.007
Quintana, M., Anderberg, P., Sanmartin Berglund, J., Frögren, J., Cano, N., Cellek, S., Zhang, J. and Garolera, M. (2020) 'Feasibility-Usability Study of a Tablet App Adapted Specifically for Persons with Cognitive Impairment-SMART4MD (Support Monitoring and Reminder Technology for Mild Dementia)', International Journal of Environmental Research and Public Health, 17(18), pp. 6816. Available at: https://doi.org/10.3390/ijerph17186816
Ilg, M. M., Stafford, S. J., Mateus, M., Bustin, S. A., Carpenter, M. J., Muneer, A., Bivalacqua, T. J., Ralph, D. J. and Cellek, S. (2020) #Phosphodiesterase Type 5 Inhibitors and Selective Estrogen Receptor Modulators Can Prevent But Not Reverse Myofibroblast Transformation in Peyronie's Disease', J Sex Med, 17(10), pp. 1848-1864. Available at: https://doi.org/10.1016/j.jsxm.2020.06.022
Ilg, M. M. and Cellek, S. (2020) 'Unwinding Fibrosis in Peyronie's Disease', J Sex Med,. 17(5), pp. 838-840.
Milenkovic, U., Ilg. M. M., Cellek, S. and Albersen, M. (2019) 'Pathophysiology and Future Therapeutic Perspectives for Resolving Fibrosis in Peyronie's Disease', Sex Med Rev,, 7(4), pp. 679-689.
Milenkovic, U., Ilg, M., Cellek, S. and Albersen, M. (2019) 'What role do pharmaceuticals play in the treatment of Peyronie's disease and is there a need for new emerging drugs?', Expert Opin Emerg Drugs,, 24(1), pp. 1-4.
Ilg, M. M., Mateus, M., Stebbeds, W. J., Milenkovic, U., Christopher, N., Muneer, A., Albersen, M., Ralph, D. J. and Cellek, S. (2019) 'Antifibrotic Synergy Between Phosphodiesterase Type 5 Inhibitors and Selective Oestrogen Receptor Modulators in Peyronie's Disease Models', Eur Urol,, 75(2), pp. 329-340.
Milenkovic, U., Ilg, M. M., Zuccato, C., Ramazani, Y., De Ridder, D., Albersen, M. (2019) 'Simvastatin and the Rho-kinase inhibitor Y-27632 prevent myofibroblast transformation in Peyronie's disease-derived fibroblasts via inhibition of YAP/TAZ nuclear translocation', BJU Int,, 123(4), pp. 703-715.
Mateus, M., Ilg, M. M., Stebbeds, W. J., Christopher, N., Muneer, A., Ralph, D. J. and Cellek, S. (2018) 'Understanding the Role of Adenosine Receptors in the Myofibroblast Transformation in Peyronie's Disease', J Sex Med, 15(7), pp. 947-957.
Selection of conference abstracts
Lapthorn, A. R., Ilg, M. M., Dziewulski, P., Cellek, S. 2024. A novel drug combination produces a synergistic effect when inhibiting myofibroblast transformation in an in vitro model of hypertrophic scarring. British Society of Investigative Dermatology Annual Meeting.M.o<
Feltham, K., Lapthorn, A. R., Dziewulski, P., Cellek, S. 2024. Adaptation of a phenotypic screening assay to incorporate 384-well plates: Opening the door to high-throughput screening. British Society of Investigative Dermatology Annual Meeting.
Cellek, S. 2024. Novel oral drugs for Peyronie’s disease. The Annual Congress of European Society for Sexual Medicine 2024.
Harding, S. L., Ilg, M. M., Bustin, S. A., Ralph, D. J., Cellek, S. 2024. Phosphodiesterase type 5 inhibitors prevent myofibroblast transformation in Peyronie’s Disease fibroblasts through the cAMP/PKA pathway, potentially through PDE1/PDE4. The Annual Congress of European Society for Sexual Medicine 2024.
Ilg, M. M., Bustin, S. A., Ralph, D. J., Cellek, S. 2024. Extracellular vesicles isolated from Peyronie’s disease-derived cells can prevent TGF-ß 1-induced myofibroblast transformation through TSG-6. The Annual Congress of European Society for Sexual Medicine 2024.
Cellek, S. 2024. Challenges in translational medicine with special focus on sexual medicine. The Annual Congress of European Society for Sexual Medicine 2024.
Ilg, M. M. 2024. How to set up a Preclinical Research lab. The Annual Congress of European Society for Sexual Medicine 2024.
Ilg, M. M., Ralph, D. J., Cellek, S., 2022. Investigating the role of extracellular vesicles in fibrosis with an in vitro model of Peyronie’s disease. International Society for Extracellular Vesicles Conference (ISEV2022), May 2022, Lyon, France.
Ilg, M. M., Lapthorn, A. R., Dziewulski, P., Ralph, D. J., Cellek, S., 2022. Repurposing Drugs for Fibrotic Diseases Using Phenotypic Screening. Drug Repurposing – II Conference, May 2022, London, UK.
Ilg, M. M., Harding, S., Lapthorn, A. R., Kirvell, S., Schurman, N., Church, S., Ralph, D. J., Bustin, S., Cellek, S., 2022. Defining a temporal gene expression profile of myofibroblast transformation in Peyronie’s disease. The Congress of European Society for Sexual Medicine 2022 (online).
Ilg, M. M., Dyer, P., Bustin, S., Ralph, D. J., Cellek, S., 2022. Investigating the role of extracellular vesicles in Peyronie’s disease. The Congress of European Society for Sexual Medicine 2022 (online).
Ilg, M. M., Ralph, D. J., Cellek, S., 2022. Statins synergize with other drugs to prevent myofibroblast transformation in in vitro model of Peyronie’s disease. The Congress of European Society for Sexual Medicine 2022 (online).
Megson, M., Merrett, C., Ilg, M. M., Cellek, S., Ralph, D. J., 2022. Can tamoxifen and a PDE5 inhibitor slow the progression of Peyronie’s disease? The Congress of European Society for Sexual Medicine 2022 (online).
Lapthorn, A. R., Ilg, M. M., Sullivan, J. S., Dziewulski, P., Cellek, S., 2022. Investigating if hydroxypyridone anti-fungals can reverse myofibroblast transformation in in vitro models of dermal scarring. The Danish Research Foundation - Extracellular Matrix Pharmacology Congress; 23-25 June 2022, Copenhagen, Denmark.
Lapthorn, A. R., Ilg, M. M., Sullivan, J. S., Dziewulski, P., Cellek, S., 2022. Hydroxypyridone anti-fungals display anti-fibrotic effects in in vitro models of hypertrophic scarring. British Journal of Dermatology, 186(6), e223. doi: 10.1111/bjd.21248
Lapthorn, A. R., Ilg, M. M., Harding, S. L., Sullivan, J. S., Dziewulski, P., Shelley, O. P., Cellek, S., 2022. Using phenotypic screening to identify novel treatments for fibrotic disorders. International Journal of Experimental Pathology, 102, A1-A17.
Lapthorn, A. R., Ilg, M. M., Sullivan, J. S., Dziewulski, P., Shelley, O. P., Cellek, S., 2022. High-throughput screening reveals 90 hits that can inhibit myofibroblast transformation in an in vitro model of dermal scarring. British Journal of Dermatology, 187(1), e35. doi: 10.1111/bjd.20477
Lapthorn, A. R., Ilg, M. M., Sullivan, J. S., Dziewulski, P., Shelley, O. P., Cellek S., 2022. Screening of 1,954 FDA-approved drugs reveals 90 hits with anti-myofibroblast activity using an in vitro model of cutaneous scarring. British Journal of Pharmacology, 178(2), pp. 411. doi: 10.1111/bph.15316
Ilg, M. M., Lapthorn, A. R., Muneer, A., Christopher, N., Cellek, S., Ralph, D. J., 2020. High-throughput phenotypic screening campaign of 1,954 FDA-approved drugs reveals 41 hits with anti-myofibroblast activity in an in vitro model of Peyronie’s disease. J Sex Med, 17(6), S129.
Ilg, M. M., Stebbeds, W. J., Parnham, A., Garaffa, G., Muneer, A., Christopher, N., Cellek, S., Ralph, D. J., 2019. Vardenafil, tamoxifen and their combination can prevent but not reverse TGF-beta1-induced myofibroblast transformation of TA-derived cells. J Sex Med, 16(5), S11.
Milenkovic, U., Janky, R., Hatzichristodoulou, G., van Renterghem, K., Cellek, S., Bivalacqua, T., De Ridder, D., Albersen, M., 2019. Transcriptome-wide analysis of Peyronie’s disease plaques using RNA sequencing uncovers targetable signalling pathways for medical therapy. J Sex Med, 16(5), S11-S12.
Lapthorn, A. R., Ilg, M. M., Sullivan J. V., Dziewulski, P., Cellek, S., 2019. Development of a high-throughput, cell-based phenotypic assay to identify novel anti-fibrotic medicines to prevent scar formation after burn injury. J Invest Dermatol, 139(5), S122.
Milenkovic, U., Janky, R., Hatzichristodoulou, G., van Renterghem, K., Cellek, S., Bivalacqua, T., De Ridder, D., Albersen, M., 2019. Peyronie’s disease plaque transcriptome-wide analysis using RNA sequencing reveals targetable signalling pathways for medical treatment. J Urol, 201(4), E860-E861.
Ilg, M. M., Mateus, M., Stebbeds, W., Milenkovic, U., Muneer, A., Christopher, N., Albersen, M., Ralph, D. J., Cellek, S., 2018. PDE5 inhibitors and selective oestrogen receptor modulators exert anti-fibrotic synergy in in vitro and in vivo models of Peyronie's disease. Int J Exp Path, 99(6), A44-A45.
Ilg, M. M., Milenkovic, U., Muneer, A., Cellek, S., Ralph, D. J., 2018. Synergy Between Vardenafil and Tamoxifen in a Rat Model of Peyronie’s Disease. Eur Urol, 17(2), e1387.
Ilg, M. M., Mateus, M., Stebbeds, W. J., Raheem, B. A. A., Spilotros, M., Capece, M., Parnham, A., Garaffa, G., Muneer, A., Christopher, N., Cellek, S., Ralph, D. J., 2017. Development and validation of a phenotypic high-throughput, cell-based assay for anti-myofibroblast activity in Peyronie’s disease. Eur Urol, 16(3), e1937-e1938.
Mateus, M., Stebbeds, W. J., Ameyaw, B., Raheem, B. A. A., Spilotros, M., Garaffa, G., Muneer, A., Christopher, N., Cellek, S., Ralph, D. J., 2016. First results from a novel cell-based assay for anti-myofibroblast activity in Peyronie's disease. J Sex Med, 13(5), S89.
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