Wellington V. Cardoso, M.D., Ph.D.

Faculty and Fellows


cardoso-portraitProfessor of Medicine and Pathology
Director, Lung Development Program

Medical School & Internship: University of Brasilia (Brazil)
Residency: Pathology – University of Brasilia (Brazil)
PhD: University of Sao Paulo (Brazil)
Postdoctoral Training: University of British Columbia, Dept. of Pathology (Vancouver/Canada); Boston University, Dept. of Medicine, Pulmonary Center (Boston, MA)

Research Interests:

  • Mechanisms of lung progenitor cell specification
  • Control of lung epithelial morphogenesis and differentiation by retinoids, fibroblast growth factors and Notch.
  • Role of developmental signals in lung disease.

Our studies focus on the mechanisms by which respiratory progenitor cells are specified, expanded and patterned during the initial stages of lung development. We have been particularly interested in understanding the role of pathways, such as the Fgf, retinoic acid (RA) and Notch in lung formation. Our studies show that the vitamin A derivative retinoic acid is a major regulatory signal integrating multiple pathways in the foregut mesoderm to regulate formation of the lung primordium. Disruption of RA interactions with Tgfb and Fgf10 results in the lung agenesis classically reported in Vitamin-A deficient embryos. We are also interested in understanding how lung progenitors give rise to the ciliated, secretory and neuroendocrine cells that populate the airway epithelium. We have shown that the Notch pathway regulates the balance of distal and proximal progenitors in the developing lung epithelium. More recently found that secretory Clara cells cannot form in the absence of Notch and airways become overpopulated with ciliated cells. These findings provide insights into the regulation of progenitor cell fate relevant to disease conditions, such as asthma and chronic obstructive pulmonary disease (COPD), in which airways have overabundance of secretory cells and paucity of ciliated cells. To address these problems our lab uses a variety of approaches, including mouse transgenic/knockout technologies, cell and organ culture techniques, gene discovery tools, large scale in situ hybridization, immunohistochemistry and confocal microscopy, among others. Our research provides insights into basic mechanisms of lung development and stem cell/progenitor cell biology that are likely to have an impact in our understanding of lung repair and cancer.

Selected Recent Publications:

  1. Tsao PN, Vasconcelos M, Izvolsky KI, Qian J, Lu J, Cardoso WV. Notch signaling controls the balance of ciliated and secretory cell fates in developing airways. Development 136: 2297-2307, 2009.
  2. Tsao PN, Chen F, Izvolsky KI, Walker J, Kukuruzinska MA, Lu J, Cardoso WV. Gamma-secretase activation of notch signaling regulates the balance of proximal and distal fates in progenitor cells of the developing lung. J. Biol. Chem. 283:29532-29544, 2008.
  3. Chen F., Desai T., Qian J., Niederreither K., Lu J, and Cardoso WV. Inhibition of Tgf beta signalling by endogenous retinoic acid is essential for primary lung bud induction Development 134: 2969-2979, 2007.
  4. Izvolsky KI, Lu J, Martin G, Albrecht K, and Cardoso WV. Systemic inactivation of Hs6st1 in mice is associated with late postnatal mortality without major defects in organogenesis. Genesis 46:8-18, 2008.
  5. Lü J, Qian J, Keppler D, Cardoso WV. Cathespin H is an FGF10 Target Involved in BMP4 Degradation during Mouse Lung Branching Morphogenesis J. Biol Chem 282:22176–22184, 2007.
  6. Desai T, Chen F., Lu J, Qian J, Niederreither K., Dollé, P., Chambon, P., and Cardoso WV. Distinct roles for retinoic acid receptors alpha and beta in early lung morphogenesis. Dev. Biol., 291:12-24, 2006.
  7. Cardoso, WV and Lu, J. Regulation of early lung development: questions, facts and controversies. Development 133: 1161-1624, 2006.

Selected Reprints:

  1. Tsao PN, Vasconcelos M, Izvolsky KI, Qian J, Lu J, Cardoso WV. Notch signaling controls the balance of ciliated and secretory cell fates in developing airways. Development 136: 2297-2307, 2009.
  2. Tsao PN, Chen F, Izvolsky KI, Walker J, Kukuruzinska MA, Lu J, Cardoso WV. Gamma-secretase activation of notch signaling regulates the balance of proximal and distal fates in progenitor cells of the developing lung. J. Biol. Chem. 283:29532-29544, 2008.
  3. Chen F., Desai T., Qian J., Niederreither K., Lu J, and Cardoso WV. Inhibition of Tgf beta signalling by endogenous retinoic acid is essential for primary lung bud induction Development 134: 2969-2979, 2007.
  4. Cardoso , WV and Lu, J. Regulation of early lung development: questions, facts and controversies. Development 133: 1161-1624, 2006.

Links:

  1. PubMed Cardoso W
  2. Cardoso Lab
  3. Developmental Biology Group: http://www.bumc.bu.edu/pulmonary/research/basicscienceresearch/developmentalbio/

Press releases: