Drugs Targets and Biomarkers

Drugs Targets and Biomarkers

The DTB group is deeply committed to the elucidation of the underlying causes and mechanisms of health, aging and disease, as well as to the identification of biomarkers and discovery of new therapeutic targets/drugs.

The DTB group has identified key structural features and anti-tumor properties of newly designed/synthesized potent aromatase inhibitors (AI) contributing to clarify the biological mechanisms of the steroidal AI exemestane and its metabolites in sensitive and resistant breast cancer cells. In chronic kidney disease (CKD) anemia, the group also showed that rHuEPO hyporesponsiveness was associated with a high systemic and renal inflammatory condition, favoring hypoxia and triggering an increase in renal expression of HIF-1-alpha, TGF-beta-1 and CTGF that will further aggravate renal fibrosis and inflammation and promote disease progression.

Pursuing our main goals, our research will focus on the: i) importance of cannabinoid signaling and impact of exogenous cannabinoids in reproduction/infertility; ii) acquired resistance mechanisms to AI to find new targets/drugs to improve ER+ breast cancer therapy; iii)  identification of biomarkers of initial renal damage, progression and mortality prediction, to enhance information on CKD and in the regulation of erythropoietin gene expression in CKD anemia; iv) development of educational programs and interventions for the elderly and health professionals to improve therapy adherence and prevent/mitigate frailty, and tools to evaluate implementation of technological solutions in old-aged.

In 2013-2017 the group has published 160 WoS papers, with 980 citations as well as 20 books/book chapters; supervised 16 PhD and 33 MSc theses. The DTB members have participated in 8 international projects (3 of which as PI) and 8 national projects (3 as PI), with an approximate funding of 0.7 M€.

DTB Research Labs
Recent publications
Borges, M; Silva, TM; Brito, C; Teixeira, N; Roberts, CW. 2019. How does toxoplasmosis affect the maternal-foetal immune interface and pregnancy?. PARASITE IMMUNOLOGY, 41, DOI: 10.1111/pim.12606
Kohlova, M; Amorim, CG; Araujo, A; Santos-Silva, A; Solich, P; Montenegro, MCBSM. 2019. The biocompatibility and bioactivity of hemodialysis membranes: their impact in end-stage renal disease. JOURNAL OF ARTIFICIAL ORGANS, 22, DOI: 10.1007/s10047-018-1059-9
Sa, SI; Maia, J; Bhowmick, N; Silva, SM; Silva, A; Correia-da-Silva, G; Teixeira, N; Fonseca, BM. 2019. Uterine histopathological changes induced by acute administration of tamoxifen and its modulation by sex steroid hormones. TOXICOLOGY AND APPLIED PHARMACOLOGY, 363, DOI: 10.1016/j.taap.2018.11.015
Fonseca, BM; Fernandes, R; Almada, M; Santos, M; Carvalho, F; Teixeira, NA; Correia-da-Silva, G. 2019. Synthetic cannabinoids and endometrial stromal cell fate: Dissimilar effects of JWH-122, UR-144 and WIN55,212-2. TOXICOLOGY, 413, DOI: 10.1016/j.tox.2018.11.006
Roleira, FMF; Varela, C; Amaral, C; Costa, SC; Correia-da-Silva, G; Moraca, F; Costa, G; Alcaro, S; Teixeira, NAA; da Silva, EJT. 2019. C-6 alpha- vs C-7 alpha-Substituted Steroidal Aromatase Inhibitors: Which Is Better? Synthesis, Biochemical Evaluation, Docking Studies, and Structure-Activity Relationships. JOURNAL OF MEDICINAL CHEMISTRY, 62, DOI: 10.1021/acs.jmedchem.9b00157