In the past year, the efforts funded by this award have yielded substantial progress in a number of areas. Our laboratory has published eight papers including a number of novel findings. We have made progress toward understanding how the Myc protein functions in stem cells and in cancer cells. In part this work has related to an important, yet poorly understood Myc co-factor called Miz-1. Our lab has determined how Miz-1 binds DNA and discovered two novel DNA motif sequences bound by Miz-1. Through these motifs Miz-1 strongly activates transcription of target genes. We are now trying to understand how this motif may related to Myc. We are also investigating how Myc may influence the global DNA methylation state of human embryonic stem cells. We have also determined that other factors in some ways act like Myc in that they are both oncogenes when overexpressed and factors that at normal levels play important roles in human pluripotent stem cells. More specifically we have found that the important pluripotency factors DPPA2 and DPPA4 are also, when expressed, able to cause cancer formation. This work published this year makes a big step forward in our understanding of the key relationship between stem cells and cancer cells. We have also investigated a novel factor called histone variant H3.3 and published two papers on this factor this year. Histone H3.3 is a fascinating molecule because it again is linked to both normal stem cell function and cancer. It is mutated in a devastating childhood tumor called glioblastoma. At the same time, our data suggests key normal roles for H3.3 in specific stem cells including germ stem cells that give rise to eggs and sperm. We published the first ever mouse knockout study of H3.3, which provided a window both into the normal and cancer-related functions of H3.3. We’ve also been studying how human ES cells and iPS cells behave in vivo in the brain with some fascinating results. Our overall goals are to enhance knowledge of stem cells and cancer and in so doing make stem cell-based regenerative medicine therapies safer and to catalyze the development of new cancer therapies. In the past year we have made a major leap forward toward these goals.