The R&D Lab develops research, knowledge transfer and consulting services in biology, biotechnology and medicine of reproductive and developmental processes in animals, including lab comparative medicine models for other animal species and humans. The R&D Lab performs fundamental, applied and translational research, involving a high level of interdisciplinary collaboration within the lab, with CIISA’s and other national labs, and of internationalization. This interdisciplinary and translational atmosphere is well reflected in the broad academic backgrounds of R&D Lab team members, PhD students and postdoctoral fellows (veterinary doctors, medical doctors, animal scientists, biologists, biotechnologists, microbiologists and health technicians). The R&D Lab displays state-of-art facilities and expertise in reproductive assessment and technologies at the animal, endocrine, tissue, cellular and molecular levels. The R&D Lab runs a transgenic mouse setting, involving several own transgenic and genetic knock-out and knock-in mutants, which are ancillary tools in embryonic and postnatal normal and abnormal development, including cancer. The R&D Lab is also in the front of research on the interactions between host and infectious agents causing reproductive failure is animal species. Technology transfer, scientific and technical consulting and formation are provided to other national and international reproductive labs, pharmaceutic companies, farmer’s cooperatives and animal breeders
Notch signaling in tumour development
A new model of adult physiological and pathological angiogenesis was proposed in which endothelial Jagged1 binds to and preferentially activates Notch4 receptor in the endothelial layer, directing the Notch4 expressing cells to differentiate and transform into smooth muscle cell (SMC), locally, while Dll4 ligand binds to and activates Notch1, leading to the transcription of Jag1, promoting vascular maturation downstream of VEGF.
Endothelial specific Dll4loss-of-function compromised both tumor growth and metastasis. Regarding tumor growth, endothelial Dll4 knockout stimulates the development of a dense but leaky vasculature, immature and non-functional, which ends up undergoing regression, thus limiting tumor burden. Most importantly, the metastasis process is impaired, by the specific effect of endothelial Dll4 inhibition. Not only endothelial Dll4 inhibition is responsible for a reduction in epithelial-to-mesenchimal transition, as it seems to lead to a decrease of cancer stem cell clone selection in the primary tumor.
Murta, D., Batista, M., Silva, E., Trindade, A., Henrique, D., Duarte, A., Lopes da Costa, L. (2013). Dynamics of Notch pathway expression during mouse testis post-natal development and along the spermatogenic cycle. PLoS ONE8(8): e72767
Galvão A., L. Valente, D.J. Skarzynski, A. Szóstek, K.K. Piotrowska-Tomala, D. Ramilo, M.R. Rebordão, L. Mateus, G. Ferreira-Dias (2013). Effect of cytokines and ovarian steroids on equine endometrium: an in vitro study. Reproduction, Fertility and Development, 25(7):985-997.
Pimenta, J Sardinha, CC Marques, A Domingos, MC Baptista, JP Barbas, IC Domingos, P. Mesquita, P Pessa, R Soares, A Viegas, E Cabrita, A.E.M. Horta, CA Fontes, JAM Prates, RMLN Pereira (2013). Inhibition of ovine in vitro fertilization by anti-Prt antibody. Hypothetical model for Prt-ZP interaction. Reproductive Biology and Endocrinology, 11:25.
Murta, D., Batista, M., Trindade, A., Silva, E., Henrique, D., Duarte, A., Lopes-da-Costa, L. (2014). In vivo Notch signaling blockade induces abnormal spermatogenesis in the mouse. PLoS ONE9(11): e113365
Henriques S, Silva E, Lemsaddek A, Lopes-da-Costa L, Mateus L. (2014). Genotypic and phenotypic comparison of Escherichia coli from uterine infections with different outcomes: clinical metritis in the cow and pyometra in the bitch, Veterinary Microbiology, 170:109-116.
Galvão A, D.J. Skarzynski, G. Ferreira-Dias (2015). Nodal promotes functional luteolysis via downregulation of progesterone and prostaglandins E2 and promotion of PGF2 alpha synthetic pathways in mare corpus luteum. Endocrinology. 157(2):858-71.
Pedrosa AR, Trindade A, Carvalho C, Graça J, Carvalho S, Peleteiro MC, Adams RH and Duarte A. (2015). Endothelial Jagged1 promotes solid tumor growth through both pro-angiogenic and angiocrine functions. Oncotarget, 6(27), 24404-24423.
Pedrosa AR, Trindade A, Fernandes AC, Carvalho C, Gigante J, Tavares AT, Diéguez-Hurtado R, Yagita H, Adams RH and Duarte A. (2015). Endothelial JAGGED1 antagonizes dll4 regulation of endothelial branching and promotes vascular maturation downstream of dll4/notch1. Arteriosclerosis, thrombosis, and vascular biology35(5), 1134-1146.
Henriques S., Silva E., Silva M.F., Carvalho S., Diniz P., Lopes-da-Costa L., Mateus L. Immunomodulation in the canine endometrium by uteropathogenic Escherichia coli. Veterinary Research, 2016, 47:114.