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  • Era bioquímica/genómica: critérios de inclusão e questões técnicas
    Publication . da Silva Gaspar, Paulo Jorge Miranda; Gaspar
    Newborn screening has evolved significantly in the biochemical and pilot studies of genomic, enabling the early detection of a broad range of congenital disorders. The shift from traditional biochemical assays to high-throughput tandem mass spectrometry and next-generation sequencing has broadened the spectrum of identifiable conditions, including metabolic, endocrine, hematological, and immunological diseases, as well as rare genetic syndromes. These technological advances enable presymptomatic diagnosis and prompt initiation of life-saving therapies, significantly improving long-term outcomes. However, the integration of genomic technologies introduces a host of technical challenges, including the standardization and validation assays, the interpretation and classification of genetic variants of unknown significance, and the management of incidental or secondary findings unrelated to the original screening purpose. Additional challenges involve the integration of large-scale data into healthcare systems, the need for robust data privacy protections, and the development of clear communication strategies for families. Addressing these technical, ethical, and logistical challenges is crucial to realizing the full potential of newborn screening in the modern era while ensuring responsible program expansion and equitable access.
    2025-10-10Documento de conferência Acesso restrito Ver mais
  • Impact of SHC-1 adaptor protein inhibitors on the plasma membrane abundance of the CFTR channel in epithelial cells
    Publication . Barros, Patrícia; Pereira, Mariana F.L.; Tomilev, Alexey; Cortopassi, Gino; Jordan, Peter; Matos, Paulo
    CFTR is a chloride and bicarbonate channel essential for ionic homeostasis in epithelial cells, and its plasma membrane (PM) abundance is often downregulated in chronic obstructive pulmonary disease (COPD) and colon cancer (CRC). CFTR endocytosis is promoted by Y512 phosphorylation by spleen tyrosine kinase, mediated by SHC-1, a phospho-tyrosine adaptor in MAPK signaling. Since the drug idebenone (IDE) disrupts SHC-1/phospho-insulin receptor interaction in hepatocytes, we tested its effects on CFTR internalization. In CFBE airway cells, IDE and a novel SHC-1 inhibitor (110#3) increased CFTR PM levels but also elevated PM levels of GLUT1 and E-cadherin, indicating a MAPK signaling-independent, non-specific action. Moreover, neither compound affected CFTR PM abundance or MAPK activity in 16HBE airway or Caco-2 intestinal cells. These findings underscore the context-dependent nature of SHC-1 signaling, suggesting IDE and related compounds may not universally disrupt SHC-1 interactions, or specifically block CFTR internalization in the airway or CRC cells.
    2025-10-10Documento de conferência Acesso aberto Ver mais