Martin Post, PhD, DVM
Head & Senior Scientist
Physiology & Experimental Medicine
University of Toronto
Depts. of Laboratory Medicine & Pathology, Paediatrics & Physiology
Canada Research ChairCanada Research Chair
Fetal, Neonatal & Maternal Health
Martin Post received his PhD from the University of Utretcht in Utrecht, The Netherlands in 1982. Following postdoctoral research training at Harvard Medical School, he was appointed as an Assistant Professor at Harvard in 1985. This was followed by a move to SickKids in 1986.
Dr. Post is the head of the Physiology & Experimental Medicine Research Program. Different areas of study in this program are: lung and cardiovascular physiology; imaging; metabolism and nutrition; infectious diseases; pharmacology; and experimental medicine.
- Lung development
- Lung cell growth
- Lung lipids and proteins
- Lung stretch and ventilation
- Placental development and preeclampsia
Preterm birth will occur in 5 to 10 per cent of all pregnancies, leading to 75 per cent of the early (neonatal) mortality and long-term disability (including cerebral palsy, deafness, blindness, mental and respiratory problems). These complications lead to a high emotional stress for the family and result in tremendous costs to the health care system.
One major complication associated with preterm birth is immaturity of the lung and, despite modern management, such as the use of surfactant and newer modes of neonatal ventilation; pulmonary immaturity remains a leading cause of neonatal morbidity and mortality. The aim of my research program is to understand the cellular and molecular physiological mechanisms that direct lung development with the long term objective to use the information to develop new therapeutic strategies or to improve existing therapies.
My research program is focused on three related areas of lung development:
1. Fetal lung formation: Lung morphogenesis results from multiple interacting signalling pathways. Although great strides have been made in elucidating some of the signalling pathways that contribute to lung development there remain many gaps in our knowledge. Our long-term goal is to integrate the identified signalling pathways in a morphogenetic map, which can then be used to model aberrant lung development. Improved understanding of the molecular mechanisms regulating pulmonary airway and vascular morphogenesis may provide targets for accelerating lung growth and maturation. This may eventually translate into therapy to counter adverse lung development as well as provide cues for lung regeneration in patients with end-stage lung disease.
2. Lung stretch and ventilation: In 1990, we established a new area of research in the laboratory, namely mechanical forces and lung cell function. Specifically, we focused on the role of fetal breathing movements (intermittent strain) on fetal lung growth. Fetal lung cells are subjected in utero to fetal breathing movements (FBM), which are essential for normal lung development. Lung hypoplasia as a consequence of altered FBMs (e.g. congenital diaphragmatic hernia, congenital pleural effusions, phrenic nerve agenesis, thoracic tumours) is a well recognized phenomenon. In addition, respiratory failure necessitating mechanical ventilation is a common clinical scenario which can lead to lung injury and fibrosis. When this intervention is required in the neonatal period, developing lungs that are still forming distal air exchange units are at risk for altered growth and development, as well as fibrosis. Our long term goal is to understand the cellular signalling leading to cell growth and differentiation during normal and, in particular, aberrant mechanical stretching of fetal lung cells.
3. Pulmonary surfactant: Pulmonary surfactant is a lipoprotein that is synthesized and secreted by the alveolar type II epithelial cell into the thin liquid layer that lines the epithelium. Phosphatidylcholine (PC) is the major component of pulmonary surfactant. The increased production of pulmonary surfactant during the latter part of gestation is of paramount importance for the ability of the newborn to establish regular air-breathing. Surfactant deficiency due to lung immaturity is a main factor responsible for the respiratory distress syndrome in premature neonates. Our ultimate goal is to understand the developmental regulation of surfactant PC synthesis.
Other areas of lung research relates to asthma and ventilation lung injuries. In collaboration with Drs. Kavanagh, McKerlie and Pace-Asciak my lab is investigating the role of bioactive lipids, such as hepoxillins, in the onset of asthma and subsequent airway remodeling. Bioactive lipid molecules are also involved in ventilation-induced lung injuries and in collaboration with Dr. Kavanagh we are studying if blockage of their generation can ameliorate the injury.
In collaboration with Dr. I. Caniggia, of Mount Sinai Hospital, my lab is also studying human placental development. We are particularly interested in the normal and abnormal regulation of early human trophoblast differentiation by changes in oxygen tension.
Future Research Interests
- To develop objective measurements of airway inflammation and lung function in infants.
- To identify diagnostic markers for asthma and COPD
- To test the potential for embryonic stem cells to differentiate in (bronchiolar) alveolar lung cells.
- To test the repair potential of mesenchymal stem cells in animal models of bronchpulmonary dysplasia and emphysema.
- To investigate the role of epigenetics in lung and placental disease.
Role of mechanical forces on lung Development. PI: M. Post.
Molecular regulation of pulmonary phosphatidylcholine synthesis. PI. M. Post.
Mesenchymal-epithelial regulation of lung development. PI. M. Post.
Role of oxygen in regulating placental development. PI: I. Caniggia, Co-PI: M. Post.
Therapeutic potential of anti-inflammatory hepoxilin analogs. PI: M. Post. Co-PIs: B. Kavanagh, C. McKerlie, C. Pace-Asciak.
Ventilator-Induced Lung injury: Linking Gene Activation, Physiology and Outcome. PI: B. Kavanagh, Co-PI: M. Post.
The role of Bcl-2 family members in regulating placental cell fate. PI: I. Caniggia, Co-PIs: M. Post; A. Juriscova
CSCCD: Centre for the Study of Complex Childhood Diseases. Project Leader: Martin Post
Yoav Y, Nevo O, Xu J, Many A, Rolfo A, Todros T, Post M, Caniggia I. Severe IUGR pregnancies have increased placental endoglin levels: hypoxic regulation via TGFβ3. Am. J. Pathol. 172(1):77-85, 2008.
Grasso F, Engelberts D, Helm E, Frndova H, Jarvis S, Talakoub O, McKerlie C, Babyn P, Post M, Kavanagh BP. Negative-pressure ventilation: better oxygenation and less lung injury. Am. J. Respir Crit Care Med. 177(4):412-8, 2008
Ngiam N, Post M, Kavanagh B. Early growth response gene-1 (EGR-1) in acute lung injury. Am. J. Physiol. 293:L1089-1091, 2007
Soleymanlou N, Wu Y, Chijiiwa1 M, Jurisicova1 A, Zamudio S, Post M, Caniggia I. Hypoxic switch in mitochondrial Mcl-1/Mtd apoptotic rheostat contributes to human trophoblast cell death in preeclampsia. Am J Pathol.171(2):496-506. 2007
Groenman FA, Rutter M, Wang J, Caniggia I, Tibboel D, Post M. Effect of chemical stabilizers of hypoxia-inducible factor on early lung development. Am. J. Physiol. 293(3):L557-67.2007.
Copland IB, Post M. Stretch-activated signaling pathways responsible for early response gene expression in fetal lung epithelial cells. J. Cell Physiol. 210(1):133-143, 2007
Van Tuyl M, Wang J, Kuliszewski M, Liu J, Tibboel D, Post M. Angiogenic factors stimulate branching morphogenesis of sonic hedgehog deficient lungs. Dev. Biol. 303:514-526, 2007.
Deimling J, Tseu I, Thompson K, Keijzer R, Tanswell AK, Post M. Mesenchymal maintenance of distal epithelial cell phenotype during late fetal lung development. Am J Physiol Lung Cell Mol Physiol 292(3):L725-741, 2007
Copland IB, Reynaud D, Pace-Asciak C, Post M. Mechanotransduction of stretch- induced prostanoid release by fetal lung epithelial cells. Am J Physiol-Lung Cell Mol Physiol. 291(3):L487-95, 2006.
Yi M, Belcastro R, Shek S, Luo D, Post M, Tanswell AK. Fibroblast growth factor-2 and receptor-1[[alpha]](IIIc) regulate postnatal rat lung cell apoptosis. Am. J. Respir Crit Care Med. 174(5):581-9, 2006.