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Our group focuses on drug discovery and development through phenotypic screening assays rather than single-target approach. We develop and validate in vitro and in vivo phenotypic screening assays. Our in vitro cell models are mostly based on human primary cells, rather than commercially available cell lines.
Currently our group is focussing on the development of novel anti-fibrotic drugs using a phenotypic assay approach. 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 aims to develop novel anti-fibrotic medicines through phenotypic screening. 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.
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.
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.
Development of phenotypic screening assay for Peyronie’s disease in collaboration with Dr 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 funding for a clinical trial.
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 in progress.
Projects being developed: Phenotypic screening assays using human primary cardiac and lung fibroblasts.
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), 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), 1848–1864. doi:10.1016/j.jsxm.2020.06.022
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.
