Research Summary The current studies examine the molecular mechanisms linking the drivers of mitophagy and autophagy with the mechanisms governing the symmetry of cell division and stem cell expansion. It is proposed that the symmetry of cell division is a determinant of stem cell expansion and that it is the cancer stem cells that give rise to therapy resistance. We are examining the role of key pathways in this biological interface using inducible deletion mice for cyclins, NFKB and Akt1. We examine cell fate determination and its role in tumorigenesis using Dachshund transgenics. Dachshund plays a key role in specifying organismal development and the generation of tissues including the brain, yet appears to play a key role in tumorigenesis. The role of cyclins in several types of tumors are being assessed assessing the non canonical functions. The non canonical functions contribute to miRNA maturation and expression, stem cell function and heterotypic signals.