Researcher | Research Overview
The unifying theme in my research is to understand the molecular mechanisms of early cellular mechanotransduction, the process whereby cells sense and convert mechanical force into biochemical signaling. This is particularly important in understanding and designing treatment strategies for a syndrome known as Ventilator Induced Lung Injury (VILI) whereby a respirator (ventilator) used to keep patients with respiratory failure, and in particular Acute Respiratory Distress Syndrome (ARDS) alive induces inflammation and contributes to mortality via multi-organ failure and death.
My initial bench research at CHB was in the Ingber Laboratory in the Vascular Biology Program and focused on the analysis of the viscoelastic properties of individual focal adhesions (molecular structures used by cells to attach to extracellular matrix through which mechanical force is applied to cells), cellular adaptation responses to mechanical stress, and the biochemical signaling pathways responsible for these cell behaviors. These studies were made possible through the design of permanent and electromagnetic devices that were used to pull on cells through bound ligand coated magnetic beads. Our recent studies led to the discovery that force applied to vascular endothelial cells induces near instantaneous (<10 ms) activation of TRPV4 (a stretch activated membrane ion channel) leading to transient localized calcium influx. This calcium response is one of the most rapid force induced biochemical signaling events detected to date, and represents an important pharmaceutical target in the treatment of VILI as calcium initiates many mechanical signaling pathways which regulate inflammation in ARDS and VILI.
My current interest is in using an ex-vivo mouse lung ventilation perfusion model to study the mechanisms of VILI and to develop drug delivery systems (in collaboration with Dr. Dan Kohane (MIT and Dept Anesthesia/CHB) to pre-treat VILI and other diseases of the lung.
Researcher | Research Background
Dr. Matthews received an MD from McGill University in Montreal, Canada. He completed a residency in Pediatrics at Schneider Children’s Hospital in New York, and a fellowship in Pediatric Critical Care Medicine at the Hospital for Sick Children in Toronto, Canada. Following his fellowship in Toronto, he worked as a staff physician at the Massachusetts General Hospital in Boston in the Pediatric Intensive Care Unit, where he also served as the Fellowship Program Director in Pediatric Critical Care Medicine. He is currently a staff physician in the Medicine Intensive Care Unit at Children’s Hospital Boston.