Joseph Bonventre
Department of Medicine
Harvard Institutes of Medicine, Room 576
4 Blackfan Circle
Boston, MA 02115
Tel: (617) 525-5960
Fax: (617) 582-6010
Email: joseph_bonventre@hms.harvard.edu
Research Interest of Bonventre Laboratory:
1. Pathophysiology of Kidney Tubular Epithelial Injury and Chronic Fibrosis
2. Stem Cells in Repair of the Kidney
3. Biomarkers of Kidney Tubular Epithelial Injury
Pathophysiology of Kidney Tubular Injury and Chronic Fibrosis: There are many parallels between repair and the normal development of the kidney. While repair is generally considered to be adaptive it can be maladaptive, especially when the acute injury is superimposed on chronic kidney disease. The laboratory studies the factors determining the recovery of the kidney to facilitate the design of strategies to enhance and hasten adaptive recovery. These goals necessitate multiple experimental approaches. Experiments are performed on normal or genetically altered animals in order to test potential pharmacologic treatments or to test the hypothesis that a particular protein is important to the injury or repair process. Studies are done at the cellular and molecular level to determined the cellular basis of protection against injury and facilitation of repair. Studies have focused on genetic mouse models and zebrafish.
Kidney Stem Cells: The kidney has the ability to completely restore epithelial integrity after a profound injurious influence which kills many epithelial cells. While it is known that kidney possesses the intrinsic capacity for repair it is not known whether adult kidney stem cells are responsible for epithelial regeneration. Attention is now focused on the identification of intrarenal stem/precursor cells that may participate in adaptive and maladaptive repair. Genetic lineage approaches in the mouse are in place and have provided a great deal of insight into the source of the cells that replace the dead cells. Factors that are responsible for directing differentiation toward the kidney fate are being defined. Bioengineering approaches are employed to understand the optimal cell-environmental interactions that optimize kidney cell differentiation in vitro to develop kidney assist devices and in vitro approaches to kidney toxicity prediction. The lab is closely integrated into the Harvard Stem Cell Institute and benefits from close collaborations with a number of other laboratories.
Biomarkers: Reliance on insensitive current biomarkers of renal dysfunction, such as serum creatinine and blood urea nitrogen, has contributed to the slow translation of basic science discovery to therapeutically effective approaches in clinical practice. Insensitivity of commonly used biomarkers of renal dysfunction not only prevents timely diagnosis and estimation of injury severity, but also delays administration of putative therapeutic agents. We have identified and characterized Kidney Injury Molecule-1 (KIM-1) as a very sensitive and specific biomarker of proximal tubular injury in a variety of species including man. The role of KIM-1 in the injured kidney is being explored using genetic and cell biological approaches and the role of this biomarker in a large number of kidney diseases in rodents and man is being evaluated. Basic science studies are complemented with clinical studies evaluating the utility of KIM-1 and other biomarkers for kidney injury and repair.
References: For a complete listing of publications on PubMed, click here.
BBS webpage updated 12/02/2009