Leland Stanford Junior University

Tannishtha Reya

Irving L Weissman

Laurie Elizabeth Ailles

Catriona Helen M Jamieson

Roeland Nusse

Calvin Jay Kuo

Mark Lee

Methods and compositions are provided for the protection of normal cells from cytoreductive therapy that target proliferating cells, by administering an inhibitor of Wnt signaling pathways. Wnt signaling is critically important for homeostasis of the epithelial lining of the adult intestine and other proliferating normal adult tissues.

Use of WNT inhibitors to augment therapeutic index of chemotherapy

Methods and compositions are provided for the identification of stem cells and cancer stem cells. &#x3b2;-catenin is also identified as a target for the development of therapeutic moieties against hematopoietic tumors, i.e. leukemia and lymphoma cells, which may include screening assays directed at &#x3b2;-catenin, or members of the &#x3b2;-catenin signaling pathway. Cellular proliferation in hematopoietic cells can be altered by introducing stabilized &#x3b2;-catenin into a hematopoietic cell that is altered in its ability to undergo apoptosis but which is not fully transformed. The immortalized cells are useful in screening assays, and in the analysis of pathways by which hematopoietic cells undergo transformation.

Methods of identifying and isolating stem cells and cancer stem cells

Mammalian progenitor or stem cells are expanded in vitro by increasing the levels of &bgr;-catenin in the cell. The expanded cells substantially maintain their original phenotype including the ability to give rise to multiple types of differentiated cells. The intracellular levels of &bgr;-catenin may be manipulated by providing exogenous &bgr;-catenin protein to the cell, or by introduction into the cell of a genetic construct encoding &bgr;-catenin. The &bgr;-catenin may be a wild-type or stabilized mutant form of the protein. Preferably the long term cell culture medium substantially lacks stromal cells and cytokines.

Growing community of inventors

Chapel Hill, NC, United States of America

Tannishtha Reya