Edward V. Prochownik, MD, PhD

My laboratory has a long-standing interest in the oncogenic Myc transcription factor and its role not only in cancer but in normal growth and development as well. We have recently been able to overcome the long-known embryonal lethality of Myc KO mice by inactivating the gene soon after birth thereby allowing us to determine how Myc impacts normal growth and development. By following the mice over their entire life span, we have shown that they develop a marked premature aging phenotype. Surprisingly however, they live longer than control mice due to the fact that they are unable to develop tumors due to their lack of Myc. RNAseq analysis indicates that many Myc target genes are altered in aging humans, thereby indicating that the MycKO mouse represents an excellent model of human aging. Current efforts are aimed at understanding the molecular, biochemical and metabolic basis for these unexpected phenotypes. A second project concerns the use of a mouse model for the most common pediatric liver cancer, hepatoblastoma (HB). Using a variety of molecular and bio-informatics-based tools we have identified a group of 22 genes that are invariably dysregulated in mouse and human HBs, irrespective of cause, stage, growth rate or histologic subtype. They are also highly predictive of survival in human HB. We are currently over-expressing these genes using Sleeping Beauty vector-mediated over-expression or Crispr-mediated knockdown in vivo to determine whether we can alter the natural history of HBs, thus potentially identifying novel means of therapeutic intervention.