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Acute and Chronic Kidney Injury and Repair and Nephrogenesis

Dr. Bonventre’s laboratory focuses on the mechanisms of adaptive and maladaptive kidney injury and repair, creation of new kidney tissue from stem cells, and use of these structures for personalized disease modality to find new therapies. Work is done in vitro and in vivo in animals. In addition, there is a major translational project identifying and validating biomarkers of injury in human urine. Recent studies have revealed a primary role for Kidney Injury Molecule-1 (KIM-1) in fibrosis and cystic kidney disease. Dr. Bonventre’s laboratory, in collaboration with Dr. Ichimura, discovered KIM-1 and has identified KIM-1 as a proximal tubule phosphatidylserine receptor responsible for phagocytosis of apoptotic cells in the injured kidney. Recently, his laboratory, together with Dr. Humphreys’ laboratory, has identified the source of cells responsible for repair of the kidney after acute kidney injury.

Dr. Bonventre has established that adult differentiated epithelial cells can de-differentiate and divide, and in this way repair the damaged epithelium. He has discovered an important new explanation for kidney fibrosis, the final common pathway in all kidney disease. He found that cell cycle arrest, after injury, results in a pro-secretory state where the tubules generate pro-fibrogenic cytokines/growth factors that enhance interstitial matrix production and stimulate interstitial myofibroblasts to divide.

With Dr. Albert Lam, Dr. Bonventre was awarded an American Recovery and Reinvestment Act (ARRA) Challenge Grant to study the mechanisms important for directed differentiation of stem cells to kidney cells. Dr. Bonventre has recently identified mechanisms by which proximal tubule cells contribute to the development of fibrosis and CKD. He has identified new mechanisms that are important for the progression of kidney disease in diabetes. He also leads a kidney biomarker core facility that has enabled collaborations with many investigators all over the world. He has created induced pluripotent cells (iPS) from patients with polycystic kidney disease and is exploring ways to use these cells for phenotypic characterization and drug screening.

Along with Dr. Ryuji Morizane, Bonventre has established a highly efficient method for making mini-kidney structures, “nephron organoids,” from stem cells derived from a patient’s skin. These structures can be used to study abnormalities of kidney development, CKD, and the effects of toxic drugs. There is also opportunity to incorporate these structures into bioengineered devices to treat patients with acute and chronic kidney injury. Dr. Bonventre’s laboratory also recently published results showing, for the first time, successful modeling of genetic kidney disease in lab-grown “mini-kidneys.” Together with Dr. Morizane and other members of Dr. Bonventre’s laboratory, Dr. Bonventre created three-dimensional miniorgans grown in a lab dish, which can model human kidney development. These organs can be used to study diseases of the glomerulus as well as Polycystic Kidney Disease (PKD).

Dr. Bonventre has established that adult differentiated epithelial cells can de-differentiate and divide, and in this way repair the damaged epithelium. He has discovered an important new explanation for kidney fibrosis, the final common pathway in all kidney disease. He found that cell cycle arrest, after injury, results in a pro-secretory state where the tubules generate pro-fibrogenic cytokines/growth factors that enhance interstitial matrix production and stimulate interstitial myofibroblasts to divide.

Dr. Bonventre has recently identified mechanisms by which proximal tubule cells contribute to the development of fibrosis and CKD. Dr. Bonventre’s laboratory, in collaboration with Dr. Ichimura, discovered Kidney Injury Molecule-1 (KIM-1) and has identified KIM-1 as a proximal tubule phosphatidylserine receptor responsible for phagocytosis of apoptotic cells in the injured kidney. In addition to being an important urinary and blood biomarker for kidney injury, KIM-1 is an important causative agent for the development of fibrosis. He has identified new mechanisms that are important for the progression of kidney disease in diabetes.

 

 

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