Hugh O'Brodovich

Clinical Focus

• Pediatric Pulmonary
• Pulmonary Medicine/Cystic Fibrosis, Pediatric

Administrative Appointments

• Physician in Chief, Lucile Packard Children's Hospital (2008 - 2013)
• Chairman of Pediatrics, Stanford University (2008 - 2013)
• Paediatrician in Chief, Hospital for Sick Children (SickKids) (1996 - 2006)
• Chairman of Pediatrics, University of Toronto (1996 - 2006)

Honors and Awards

• President, Fleischner Society (2007)
• Fellow, Canadian Academy of Sciences (2006)
• Edwin L Kendig Award, American Academy of Pediatrics/American College of Chest Physicians (2005)
• Scientific Accomplishment Award, American Thoracic Society (2001)

Professional Education

Web Site Links

• Department of Pediatrics Stanford University

Research Interests

The laboratory’s work focuses on the lungs clearance of airspace fluids and has used the newborn as a paradigm for alveolar fluid clearance: all infants are born with “alveolar edema” yet virtually all survive this salt water drowning. In 1990, the research group discovered that when amiloride, a Na+ transport blocker, was instilled into the fluid-filled airspaces of newborn guinea pigs prior to their first breath, they developed respiratory distress, hypoxemia, and failed to clear their fetal lung liquid. This result was consistent with the hypothesis that Na+ transport was an essential process in changing the fetal lung to a post-natal lung. This finding impacted the understanding and treatment of respiratory diseases since it indicated that neonatal respiratory distress syndrome was initiated by two and not one mechanisms; the previously known relative surfactant deficiency and his lab’s observation of impaired fluid clearance from the lung’s airspaces.

The lab found that the cloned epithelial Na channel (ENaC) was present in the lung, that fetal maturity affected its expression, and that alpha, beta and gamma ENaC subunit mRNA and DLE amiloride-sensitive Na+ transport was modulated by fetal lung cell-derived matrix, glucocorticosteroids, gender hormones and activated macrophages. They found that a rise from 3 to 21% O2 increased DLE ENaC mRNA and amiloride-sensitive Na+ transport; this is mediated, in part, by reactive oxygen intermediates associated with NF-kappa B activation and is dependent upon heme-containing proteins.

The lab investigated the genomic structure (intron/exon, transcriptional start sites) of alpha and beta – ENaC subunits, the regulation of their promoters’ activities and regulatory elements functioning at the level of protein translation within the 5'UTR of alpha-ENaC. Translational efficiency is markedly different for each of the alpha, beta and gamma ENaC sub-unit mRNAs and is mediated, at least in part, via mTOR.

The...

Publications

• Glucocorticoid-mediated repression of REDD1 mRNA expression in rat fetal distal lung epithelial cells. Otulakowski G, Duan W, Sarangapani A, Gandhi S, O'Brodovich H. Pediatr Res. 2009; 65 (5): 514-9
• Protease-activated receptor (Par)1 alters bioelectric properties of distal lung epithelia without compromising barrier function. Moraes TJ, Rafii B, Niessen F, Suzuki T, Martin R, Vachon E, Vogel W, Ruf W, O'Brodovich H, Downey GP. Exp Lung Res. 2009; 35 (2): 136-54
• Pulmonary neuroendocrine cell-secreted factors may alter fetal lung liquid clearance. Gandhi SG, Law C, Duan W, Otulakowski G, O'Brodovich H. Pediatr Res. 2009; 65 (3): 274-8
• Global and gene-specific translational regulation in rat lung development. Otulakowski G, Duan W, O'Brodovich H. Am J Respir Cell Mol Biol. 2009; 40 (5): 555-67
• Visualizing water clearance in the lung with MRI. Vidarsson L, Helm E, O'Brodovich H, Macgowan CK. Magn Reson Med. 2008; 60 (1): 230-5