The cause of injury and loss of blood-forming stem cells (Hematopoietic Stem Cells, HSC) in Fanconi anemia is due to abnormal repair of a specific type of DNA damage in which two DNA strands get permanently knotted to each other. This type of injury probably occurs frequently but is normally repaired by the proteins made by the genes which are mutated in FA. When the FA genes are mutated, cells cannot repair the tangled DNA. DNA knots are caused by chemical reactions between the DNA strands that are induced by a class of chemicals called aldehydes, which are naturally present as both toxins and normal products of metabolism, for example, after drinking alcohol. Human cells have 19 different enzymes (“ALDH’s”) that convert aldehydes to less toxic substances. We think that drugs that increase the activity of ALDH’s will decrease the amount of aldehydes in HSC, thereby preventing DNA damage and preventing marrow failure in FA. We will use the grant funding to test this hypothesis.