The Rabinovitch/Bland Lab

Ongoing Research in the Laboratory of Richard Bland, M.D.

Findings of Recent Studies:

1)    Mechanical ventilation of newborn mice with air alone inhibits the formation of alveoli (A)
and pulmonary capillaries (B), and causes remodeling of the matrix elastin (C), leading to growth arrest of the developing lung - these findings were linked to TGFß activation, impaired VEGF signaling, and elastin degradation.

         Unventilated Control            Mechanical Ventilation
Microscopic images of section of lung sections obtained  from ventilated and unventilated newborn mice
A. 
Impaired Alveolar
Formation
(H&E stain)

 


B.
Reduced Capillary
Formation
(CD-31)



C.
Increased, Scattered 
Elastic Fibers
(Hart’s stain)

 

 

2)    Inhibiting lung elastase activity in newborn mice protects against many of the adverse effects of mechanical ventilation: prevents degradation and dispersion of matrix elastin, activation of TGFß, defective VEGF signaling, and apoptosis, and attenuates lung structural abnormalities that occur in response to prolonged cyclic stretch

3)    Intra-pulmonary treatment with a neutralizing antibody to TGFß normalizes VEGF signaling, prevents apoptosis and promotes lung growth during lengthy mechanical ventilation of newborn mice

Ongoing Research Projects:

1)    Studies to determine the effects of TGFß inhibition on impaired development of the pulmonary microcirculation observed in the lungs of newborn mice after prolonged mechanical ventilation

2)    Studies to assess the role of defective PDGF signaling in the pathogenesis of lung growth arrest induced by lengthy mechanical ventilation of newborn mice

3)    Studies to determine the effects of mechanical ventilation on the formation of alveoli and lung capillaries in neonatal mice that are deficient in one allele of the elastin gene (Eln+/–)

Stanford Medicine Resources:

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