Martin Post

Research Synopsis

Preterm birth occurs in 5-10% of all pregnancies, leading to 75% of the early (neonatal) mortality and long-term disability (including cerebral palsy, deafness, blindness, mental and respiratory problems). 

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 is to understand the biological and physiological mechanisms that direct lung development and the impact of preterm birth on this process.

The long term objective is to develop new therapeutic strategies, including lung regeneration, or to improve existing therapies.

Lung morphogenesis results from multiple interacting signaling pathways

Although great strides have been made in elucidating some of the signaling pathways that contribute to lung development there remain many gaps in our knowledge.

My long-term goal is to integrate the identified signaling pathways in a morphogenetic map, which can then be used to model aberrant lung development.

Mechanical ventilation is commonly used in neonatal respiratory failure, and is well known to cause -or worsen lung injury

In the neonate, developing lungs are still forming distal air exchange units: thus, mechanical ventilation can impair alveolar development by inhibiting lung cell growth, augmenting cell death and increasing inflammatory mediator expression.

We investigate the impact of ventilation (stretch) on lung cell fate in vitro and in vivo.

Emerging evidence suggests that stem cells can differentiate into lung cells

However, the environment and factors that are required for the differentiation of stem cells into lung-specific cells are largely unknown.

We are investigating the cellular commitment to a pulmonary phenotype and the potential of acellular lung scaffolds for tissue engineering.

A new exciting direction we explore is stem cell-based innate immune therapy using stem cell derived alveolar macrophages in pneumonia models. 

Sphingolipids are involved in the regulation of many cellular processes

Ceramides trigger cell death while sphingosine-1-phosphate (S1P) promotes cell survival. Thus, ceramides and S1P form a rheostat that balances apoptosis and proliferation; processes gone awry in the ventilated preterm lung.

Understanding and manipulation of the ceramide-S1P axis in the injured newborn lung may benefit its repair.

We are investigating sphingolipid metabolism in ventilated newborn animals and hyperoxia models of neonatal lung disease (i.e. BPD).

Lipidomics

Another line of investigation concerns lipidomics (large scale study of lipid quantity and function which may provide a molecular signature to a certain pathway or a disease condition). We perform lipidomic analysis to identify potential molecular lipid signatures in the tracheal fluid or sputum of (BPD, Asthma, COPD) patients as predictors and prognostic markers for outcomes.

We focus on wide screens for eicosanoids, sphingolipids (ceramides, sphingosines etc), phospholipids and lysophospholipids (PC.LPC,PE,PS, PI, PG etc), phosphatidic acids and oxidized lipids. 

Preeclampsia

Preterm birth can be due to preeclampsia, a complex and serious disorder of human pregnancy and the leading cause of fetal and maternal morbidity and mortality worldwide, affecting approximately 5-7% of all pregnancies.

Although, the etiology and pathophysiology of this disease remains an enigma, it is accepted that the presence of the placenta, not the fetus, is at the origin of this disease.

In collaboration with the Mother and Infant Research Group at Mt. Sinai Hospital, Toronto we investigate normal and abnormal placentation.

My Lab

My research group has state-of-the-art laboratory and office space on the 9th floor of the new SickKids research facility, the Peter Gilgan Centre for Research and Learning (PGCRL).  

The laboratory is fully equiped for molecular, cellular and physiologic research.

We have access to all SickKids core facilities providing crucial infrastructure, services and expert personnel to help us successfully deliver on our objectives, including:

• Lab Animal Services
• Embryonic Stem Cell Facility
• TCP Transgenic Facility
• Imaging Facility
• Flow Cytometry Facility
• primary access to the Analytical Facility of Bioactive Molecules specialized in metabolic research.

In addition, we have dedicated space within the animal facility for long term cardiopulmonary physiological studies.