Lloyd Cantley

C.N.H. Long Professor of Internal Medicine
Professor of Cellular and Molecular Physiology
Associate Chair for Research, Department of Internal Medicine
Section of Nephrology

Research Interests

The primary focus of our laboratory is to determine the mechanisms of renal tubule development and repair. When the kidney is injured following ischemia or toxin exposure, the remaining epithelial cells de-differentiate, spread over the denuded basement membrane, divide, and re-arrange themselves in a specific pattern to regenerate functional tubules. This process requires a complex array of events involving rearrangement of cell shape and regulation of cell-matrix and cell-cell interactions. By examining epithelial cell adhesion, migration, and branching tubulogenesis in response to growth factors such as Hepatocyte Growth Factor and Epidermal Growth Factor, we are determining the intracellular signaling events critical for tubule formation during kidney development and following injury. We have focused these efforts on the role of activation of specific MAPK isoforms as well as the PI 3-kinase in the regulation of cell morphogenesis and cell-matrix interactions.

In addition, we are examining the role of adult and embryonic stem cells in the recovery from acute tubular necrosis. We have found that bone marrow contains stromal cells that can be activated and participate in the repair process. We are presently examining what factors these cells produce and how these factors regulate the endogenous cell responses. In addition, we are studying the pathways that regulate the differentiation of embryonic stem cells to become renal tubule progenitor cells. Ultimately, we hope that the knowledge gained from these experiments will provide a much more detailed understanding of the events that promote tubule formation, and allow us to augment kidney tubule repair and prevent long-term scarring following renal injury.

PubMed Search for articles by faculty member

Selected Recent Publications

• Kale S, Karihaloo A, Clark P, Kashgarian M, Krause D, Cantley LG. Bone marrow stem cells contribute to repair of the ischemically injured renal tubule. J.Clin.Inv., 2003; 112, 42-49.
• Ishibe S., Joly D., Liu Z-X., Cantley L.G. Phosphorylation-dependent Paxillin-ERK association mediates HGF-stimulated epithelial morphogenesis. Mol. Cell, 2003; 12, 1275-1285.
• Ishibe S., Joly D., Liu Z-X, Cantley L.G. Paxillin serves as an ERK-regulated scaffold for coordinating FAK and Rac activation in epithelial morphogenesis. Mol. Cell, 2004; 16(2): 257-67.
• Cantley, LG: Adult Stem Cells and repair of the injured renal tubule. Nature Clin. Nephrol., 2005; 1(1): 22-32.
• Ishibe S., Heydu J-E., Togawa A., Marlier A., Cantley L.G. Cell confluency regulates HGF-stimulated cell morphogenesis in a ?-catenin dependent manner. Mol. Cell. Biol., 2006; 26(24): 9232-43.
• Bi B., Schmitt R., Israilova M., Nishio H., Cantley, L.G. Stromal cells protect against acute tubular injury via an endocrine effect. J. Am. Soc. Nephrol., 2007; 18(9):2486-96.

Education:	B.S. 1977 West Virginia Wesleyan College M.D. 1981 West Virginia School of Medicine
Training:	Resident: North Carolina Memorial Hospital Fellowships: Beth Israel Hospital

Contact

Campus Address
Section of Nephrology
Department of
Internal Medicine
Yale School of Medicine
P.O. Box 208029
New Haven, CT
06520–8029

E-mail
lloyd.cantley@yale.edu