Dermatology, Skin Biology and Pathology
The skin is a complex organ providing the interface between the external environment and the internal milieu. In humans, the skin ranks first as a source of pathology.
Psoriasis and non-melanoma skin cancers are highly prevalent and share in common a hyperproliferative state, increased angiogenesis and a prominent host immune response. Psoriasis is indeed an autoimmune disease mostly driven by immune cells that produce, or respond to, the cytokines IL-17 and IL-23. The disease is characterized by frequent relapse, typically in previously affected body areas, invoking some sort of tissue immune memory. We are currently testing whether disease memory is altered in immunodeficient individuals, and why the increased cellular proliferation associated with psoriasis does not directly translate into increased incidence of skin cancers. We are also searching for biomarkers (eg complement factor H) that can predict disease relapse.
Non-melanoma skin cancers, namely basal cell carcinomas and squamous cell carcinomas, trigger a strong host immune response. We have found that the inflammatory infiltrates within these tumours comprise a high fraction of IL-17-producing cells. We are addressing whether the IL-23/IL-17 axis is involved in the increased angiogenesis associated with these tumours.
Finally, we are identifying the photoproducts of widely used drugs that act as photo-carcinogens and their mechanisms of skin carcinogenesis.
João Borges Costa
João Nuno Silva
Luís Miguel dos Santos Reis Soares de Almeida
Maria Clara Bicho
Miguel Duarte Botas Alpalhão
Ongoing Research Projects
2018/2021 Do differences in the lymphocytic inflammatory infiltrate account for the variations between the aggressiveness of SCCs vs BCCs? Coordinator: Daniela Cunha. Funding Agency: Almirall.
2016/2019 Th9-IL9R axis: a role in tissue memory in plaque-type psoriasis? Coordinator: Paulo Manuel Leal Filipe. Funding Agency: Novartis
Teixeira A, Morlière P, Ferreira J, Conte MA, Galmiche A, Mazière JC, Santus R, Filipe P. (2016) Interplay Between Membrane Lipid Peroxidation and Photoproduct Formation in the Ultraviolet A-Induced Phototoxicity of Vemurafenib in Skin Keratinocytes. Toxicol Sci. 154, 289-295. (Journal IF: 4.081, Citations: 1).
Pereira PD, Serra-Caetano A, Cabrita M, Bekman E, Braga J, Rino J, Santus R, Filipe PL, Sousa AE, Ferreira JA. (2017) Quantification of cell cycle kinetics by EdU (5-ethynyl-2?-deoxyuridine)-coupled-fluorescence-intensity analysis. Oncotarget 8, 40514-40532. (Journal IF: 5.168, Citations: 3).
Morlière P, Hug GL, Patterson LK, Mazière JC, Ausseil J, Dupas JL, Ducroix JP, Santus R, Filipe P. (2014) Chemistry of free radicals produced by oxidation of endogenous aminoketones. A study of 5 aminolevulinic acid and aminoacetone by fast kinetics spectroscopy. Biochim Biophys Acta. 2014 Oct; 1840 (10): 3190-7. doi: 10.1016/j.bbagen.2014.07.002. Epub 2014 Jul 10. 1840, 3190-7. (Journal IF: 4.702, Citations: 1).
Pinheiro T, Silva R, Fleming R, Gonçalves A, Barreiros MA, Silva JN, Morlière P, Santus R, Filipe P. (2014) Acta Derm Venereol. 2014 Jan; 94 (1): 14-9. doi: 10.2340/00015555-1601. Distribution and quantitation of skin iron in primary haemochromatosis: correlation with total body iron stores in patients undergoing phlebotomy. Acta Derm Venereol. 2014 Jan; 94 (1): 14-9. doi: 10.2340/00015555-1601. 94, 14-9. (Journal IF: 4.244, Citations: 6).
Morlière P, Silva AMS, Seixas RSGR, Boscá F,. Mazière J-C, Ferreira J, Santus R, Filipe P. (2018) Photosensitisation by voriconazole-N-oxide results from a sequence of solvent and pH-dependent photochemical and thermal reactions. Journal of Photochemistry & Photobiology, B: Biology, 187 (2018) 1-9.doi:10.1016/j.jphotobiol.2018.07.023 . (Journal IF: 3.165)