Fibrosis Research Group

While fibrosis is the causative pathology of more than 40% of mortality globally, 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 are now being taken to clinical studies.

Cells as viewed through a microscope

The unmet need for anti-fibrotic therapeutics has recently been highlighted by the risk of fibrotic conditions being increased by Covid-19 infection. It is now estimated that 5-30% of patients who have had severe Covid-19 infection are at the risk of developing long term lung, heart or kidney problems which are associated with fibrosis.

Moreover, the number of skin burns have increased significantly during Covid-19 lockdown; some of these burns may cause scarring, which also is a fibrotic condition. Therefore, new treatments that can prevent fibrosis formation are urgently needed. Our work towards achieving this has recently been highlighted in BBC News.

Read more about our approach:

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 mtrc@aru.ac.uk for more information.

Researchers

Current doctoral students

  • Sophie Harding
  • Matthew Megson

Past doctoral students

  • William Stebbeds
  • Marta Mateus
  • Marcus Ilg
  • Alice Lapthorn

Projects

Development of phenotypic screening assay for Peyronie’s disease in collaboration with Profs David Ralph and Asif Muneer at University College London Hospital. Current stage: the assay has been developed and validated, screened small molecule compounds; two hits validated in vitro and in vivo; now seeking adoption by NHS.

Development of phenotypic screening assay for burns patients in collaboration with Prof Peter Dziewulski, St Andrews Centre for Plastic Surgery and Burns. Current stage: Assay has been developed and validated, screened small molecule compounds; hit validation completed. Now seeking funding for clinical trials.

Other projects:

  • Development of phenotypic screening assays using human primary cardiac, intestine, liver, and lung fibroblasts.
  • The role of extracellular vesicles in fibrotic diseases.
  • Development of phenotypic screening assays for cancer metastasis.

Recent activity

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.



Key publications

Selection of full papers

Quintana, M., Anderberg, P., Sanmartin Berglund, J., Frögren, J., Cano, N., Cellek, S., Zhang, J., 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. doi: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., & 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. doi:10.1016/j.jsxm.2020.06.022

Ilg, M. M., Cellek, S., 2020. Unwinding Fibrosis in Peyronie's Disease. J Sex Med, 17(5), pp. 838-840.

Milenkovic, U., Ilg. M. M., Cellek, S., 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., 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., 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., 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.

Read more about selection of full papers.

Selection of conference abstracts

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.

Read more about selection of conference abstracts.

Contact us

Email: mtrc@aru.ac.uk

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In order to continue our essential work on developing new anti-fibrotic medicines, we need your support. Your donations will be used to purchase research material and hire new researchers and will make a big difference to the lives of thousands of patients who are waiting for a treatment. Thank you!

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