Researcher eyes tackling sepsis
"It's a devastating runaway infection." That's how Samir Parikh, MD, describes sepsis, a deadly disease that spreads swiftly through the bloodstream, often spurred on by post-surgical infections or complications of pneumonia. The widespread condition ranks among the top 10 causes of mortality in U.S. adults and is estimated to cost the health care system more than $16 billion a year.
Parikh is one of 16 young investigators who will present work at BIDMC's Research Day 2010, March 5, in Sherman Auditorium.
As a nephrologist who has witnessed the damage sepsis can cause in patients' kidneys, Parikh's research interests have focused on uncovering the cellular mechanisms responsible for the disease's cascading and devastating effects, which are triggered by rampant inflammatory responses in blood vessels throughout the body. Its destructive path through the bloodstream can result in vascular leakage, shock, multi-organ failure, and ultimately, death.
"Despite the armament of antibiotics available, these are not sufficient to combat the systemic complications people develop with sepsis," explains Parikh. "Antibiotics are critical, but we also have to fix inflammation of vessels and organs in the body, the loss of blood pressure referred to as septic shock, and the leakage of fluid out of vessels."
If the circulatory system is the highway on which sepsis travels, endothelial cells, which line the interior of blood vessels, are the pavement. Research originally begun by Parikh while a member of Vikas Sukhatme's laboratory has revealed that a molecular pathway within endothelial cells-the angiopoietin/Tie-2 system-is implicated in vascular inflammation and may be a potential marker and mediator of sepsis.
This past fall, Parikh's laboratory received a two-year grant from the National Heart, Lung, and Blood Institute, part of the American Recovery and Reinvestment Act (ARRA) funding, to enable his lab to continue this line of investigation.
"Our data has shown that when the angiopoietin/Tie2 pathway is activated, blood vessels do not leak; conversely, when the pathway is disrupted, the vascular leakage that is a hallmark of sepsis returns," he explains.
Parikh will use the ARRA funding to develop a transgenic mouse model that will enable his research team to activate and control the angiopoietin/Tie-2 pathway. Moreover, the investigators will be able to turn on the transgene in a targeted environment, such as the liver or lungs, to isolate and study angiopoietins' effect on one organ or cell at a time.
"This mouse model is an achievable project that will not only be useful for our questions in the study of sepsis, inflammation, and vascular leakage, but will also be a valuable tool for other researchers," he notes.
To learn more about research efforts in nephrology, click here.