Endothelial Sash1 Is Required for Lung Maturation through Nitric Oxide Signalling
This week we profile a recent publication in Cell Reports from the laboratory
of Dr. Aly Karsan (pictured, back row left) at BC Cancer and UBC.
Can you provide a brief overview of your lab’s current research focus?
My lab is focused on understanding post-transcriptional mechanisms of cancer resistance and progression, with a major interest in myeloid cancers. One pathway of interest is the role of innate immune signalling in vascular and hematopoietic function, both in the context of normal development and myeloid malignancies. An active area of research is in understanding the physiological role and mechanism of action of the protein Sash1, which signals downstream of the Toll-like receptor pathway.
What is the significance of the findings in this publication?
Lung immaturity is a major cause of respiratory distress and mortality in premature newborns. In this publication, we identified a role for the protein Sash1 in driving perinatal lung maturation in mice via nitric oxide signalling. Our findings suggest that nitric oxide release by endothelial cells, upon the interaction of Sash1 with β-arrestin1, is an important step in preterm alveolar maturation to allow proper lung inflation at birth.
What are the next steps for this research?
The next step for this research is to investigate the importance of Sash1 in the adult lung. Sash1 has been implicated as a tumour suppressor in various solid cancers and we are interested in looking at whether Sash1 loss in the vasculature drives lung cancer progression.
This work was funded by:
Canadian Institutes of Health Research (CIHR)