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About Sickkids
About SickKids

Neil Sweezey, MD

The Hospital for Sick Children
Staff Respirologist
Respiratory Medicine

Research Institute
Team Investigator
Translational Medicine

University of Toronto
Associate Professor
Paediatrics


Phone: 416-813-5128
Fax: 416-813-5771
Email: neil.sweezey@utoronto.ca

Research Interests

  • Effects of female sex hormones on inflammation in cystic fibrosis lung
  • Hormonal regulation of lung development

Research Activities

My laboratory addresses the effects of steroid hormones on the lung. 

The main cause of death in cystic fibrosis (CF) is the lung disease, which is in turn caused by inflammation that is aggravated and perpetuated by infection.  Our first project investigates how female sex hormones alter the severity of inflammation in CF lung. We will determine the effects of natural menstrual changes in levels of female sex hormones alter inflammation and infection in the respiratory secretions of human CF females. We will determine if a drug that blocks naturally occurring estrogen will correct the female disadvantage in CF mice.  

The second project examines how glucocorticoid hormones control lung development. We are using mouse models of lung development to clarify which lung cell types and which signaling molecules are critical to the maturing effects of glucocorticoids on the developing lung.   This subject is particularly relevant to chronic lung disease of prematurity (bronchopulmonary dysplasia), which afflicts over one third of newborns weighing < 1 kg. The overall goal of this work is to identify downstream effector targets of glucocorticoid that can stimulate newborn lung development with less adverse effects than the glucocorticoids themselves.

Future Research Interests

We are following-up on our findings, to clarify the levels of action of hormones on antenatal lung development, looking at stability and rates of synthesis of GR and CFTR at mRNA and protein levels. We are also testing potential mediators of the cell-cell interactions we have observed regulating cellular GR expression. Experiments are underway to further address the effects of hormones on the function of CFTR in fetal rat lung epithelial cells, and to clarify the factors which turn off the functional activity at term.

Publications

Nadeau K, Mandeville I, Xu M, Weiss ST, Sweezey NB, Kaplan F.   Modulation of Lgl1 by steroid, retinoic acid and Vitamin D models complex transcriptional regulation during alveolarization. Pediatric Res; 67(4):375-381, April 2010.  

Manwani N*, Gagnon S**, Post M, Joza S, Muglia L, Cornejo S, Kaplan F, Sweezey NB. Reduced Viability of Mice with Lung Epithelial-Specific Knockout of Glucocorticoid Receptor. Am. J. Respir. Cell Mol. Biol. 2009; EPub ahead of print December 30, 2009.                                   

Nemati B*, Atmodjo W**, Kaplan F, Sweezey NB. Glucocorticoid Receptor Disruption Delays Structural Maturation in the Lungs of Newborn Mice. Pediatric Pulmonology 2008 Feb;43(2):125-133    

Sweezey NB, Smith D, Corey M, Ellis L, Carpenter S, Tullis E, Durie P, O’Brodovich HM. Amiloride-Insensitive, but not Amiloride-Sensitive, Nasal PD varies with the Menstrual Cycle in CF. Pediatric Pulmonology 2007 Jun;42(6):519-24.    

Gagnon S**, Atmodjo W**, Humes D, McKerlie C, Kaplan F, Sweezey NB. Transgenic Glucocorticoid Receptor Expression Driven by the SP-C Promoter Reduces Neonatal Lung Cellularity and Midkine Expression in GRhypo Mice Biol Neonate 2006;90:46-57   

Oyewumi L*, Kaplan F, Sweezey NB. Lgl1, a mesenchymal modulator of lung epithelial morphogenesis, is a secreted glycoprotein imported by late gestation lung epithelial cells.  Biochem. J.  2003 Nov 15;376(Pt 1):61-9.

Oyewumi L*, Kaplan F, Gagnon S**, Sweezey NB. Antisense oligodeoxynucleotides decrease expression of LGL1 mRNA and protein and inhibit branching morphogenesis in fetal rat lung. Am J Respir Cell Mol Biol. 2003 Feb;28(2):232-40.

Kaplan F, Comber J, Sladek R, Hudson TJ, Muglia LJ, Macrae T,  Gagnon S**, Asada M, Brewer JA, Sweezey NB.
The growth factor midkine is modulated by both glucocorticoid and retinoid in fetal lung   development.  Am J Respir Cell Mol Biol. 2003 Jan;28(1):33-41.

Intellectual Property

Late Gestation Lung – LGL 1 Gene, Protein, Fragments and Uses Thereof
Corporate Ventures