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:

Diagram showing the Fibrosis Group's progress. Their treatment for Peyronie's disease is available as off-label prescription (early clinical results showing effect); they're seeking pharmaceutical backing to progress their treatment for hypertrophic scars to clinical trial; hit validation is in progress for their treatment for intra-abdominal adhesions; they're developing an assay for cardiac fibrosis and will begin screening fibroblasts for pulmonary fibrosis from early 2025.

Above: Diagram showing our current progress. We are at the clinical development stages for Peyronie’s disease and hypertrophic scars; hit validation stage for intra-abdominal adhesions; screen development stage for cardiac fibrosis and drug screening stage for pulmonary 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

Cells as viewed through a microscope

Current doctoral students

Past doctoral students

Collaborators

Funders

Recent activity

Dr Alice Lapthorn speaking at the British Society for Gastroenterology Annual Meeting 2024

Dr Alice Lapthorn was invited by Guts UK to give a talk at the British Society for Gastroenterology Annual Meeting (2024), which was held in Birmingham in June.



Composite image of Dr Sophie Harding and Dr Alice Lapthorn with their poster presentations at ELRIG's Drug Discovery 2024

Dr Alice Lapthorn and Dr Sophie Harding presented posters of their research at ELRIG’s Drug Discovery 2024, which was held in London in October.



Kieran Feltham with his poster presentation at the British Society of Investigative Dermatology Annual Meeting 2024

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.



Dr Sophie Harding giving a presentation at the European Society for Sexual Medicine (ESSM) Annual Congress

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.

Alice Lapthorn explaining her poster to an attendee at the STEM for Britain presentation in the House of Commons

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”.



Marcus Ilg presenting at the 24th Annual Congress of the European Society for Sexual Medicine (ESSM) in Rotterdam

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”.





Marcus Ilg standing in front of his display at the ISEV2022 conference

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.



Alice Lapthorn (right) with three other delegates at the British Society for Investigative Dermatology Annual Meeting

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 next to her poster presentation at Pharmacology 2022 @ Liverpool

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., Bustin, S. A., Ralph, D. J. and Cellek, S. (2024) ‘TGF-β1 induces formation of TSG-6-enriched extracellular vesicles in fibroblasts which can prevent myofibroblast transformation by modulating Erk1/2 phosphorylation’, Scientific Reports, 14(1), 12389. Available at: https://doi.org/10.1038/s41598-024-62123-x

Lapthorn, A. R., Harding, S. L., Feltham, K. M., Sathyananth, D., Salisbury, D. C. and Cellek, S. (2024) 'A Review of the Current Landscape of Anti-Fibrotic Medicines', Fibrosis, 2, 10005. Available at: https://doi.org/10.70322/fibrosis.2024.10005

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., Harding S. L., Ilg M. M., Khan J., Dziewulski P., Ralph D. J., Cellek, S. 2024. Phenotypic drug discovery for fibrosis – the answer to a decades old problem? ELRIG Drug Discovery 2024.

Harding S. L., Ilg, M. M., Bustin S. A., Ralph D. J., Cellek, S. 2024. Phosphodiesterase inhibition prevents myofibroblast transformation in Peyronie’s disease. ELRIG Drug Discovery 2024.

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.

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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Email: [email protected]

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