Pierre C. Dagher, MD
Associate Professor of Medicine
Director, Nephrology Fellowship Program
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Affiliations: |
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Residency: |
New York University, New York, New York
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My lab investigates the mechanisms of acute kidney injury (AKI) in animal models of ischemia-reperfusion and sepsis. In particular, we focus on the roles of the tumor suppressor p53 and Toll-like receptors in the interplay between inflammation and apoptosis in AKI.
In addition to routine genetic, biochemical and microscopic techniques, we have pioneered the use of 2-photon intravital microscopy and developed novel tools to study diverse processes involved in renal pathophysiology. These include assays to measure apoptosis, vascular damage, mitochondrial function and oxidative stress in the kidneys and livers of live animals. These novel techniques are made available to researchers from various disciplines through our O’Brien center grant.
Our studies have uncovered important species-specific roles for p53 in determining the extent and phenotype of ischemic injury to the kidney. In particular, we study the role of p53 in determining the delicate balance between tubular apoptosis and immune cell survival. These studies have evolved into the first human trial examining p53 inhibition in the prevention of hemodynamic peri-operative AKI.
Using various transgenic mice and bone marrow chimeras, we also discovered a novel pathway of kidney injury in animal models of sepsis. This pathway involves direct receptor-mediated interactions between S1 segments of proximal tubules and endotoxin and is independent of systemic cytokines. These interactions between endotoxin and S1 result in severe peroxisomal damage and oxidative stress in downstream nephronal segments. We are currently extending these studies to examine the role of specific molecules involved in Toll signaling in mediating endotoxin injury as well as the mechanisms of renal endotoxin tolerance and pre-conditioning
