DF/HCC Program Affiliation

Cancer Cell Biology

Research Abstract

The Fornace laboratory focuses on stress signaling pathways involved in the cellular responses to genotoxic as well as oncogenic stresses. Scientific contributions include an early role in the development of sensitive assays to monitor DNA damage and repair in mammalian cells, and more recently the identification and characterization of mammalian stress response genes including the discovery of some of first mammalian DNA-damage inducible genes. His laboratory is probably best known for the discovery and cloning of the gadd (growth arrest and DNA damage inducible) genes and the finding that radiation-induction of the Gadd45a gene is dependent on the tumor suppressor 53 and the ATM gene product. They were the first to demonstrate regulation of a stress gene, Gadd45a, by p53 and the key role for the p53 signaling pathway in the maintenance of genomic stability. Recent projects have focused on stress signaling and cellular responses to radiation and chemical damage including checkpoint activation, apoptosis, and DNA repair. Dr. Fornace’s laboratory has shown critical roles for the p38 MAP kinase family as a tumor suppressor and interplay between various key signaling pathways such as p53, MAP kinase, Rb, and others. These projects involve a variety of novel mouse models including gene disruption (knockout) and site-directed mutation (knockin) strategies with relevance to T-cell lymphoma, mammary cancer, skin cancer, and lung cancer. Considering the complexity of genotoxic stress responses, another major focus is the development of functional genomics and metabolomics approaches to monitor for stress responses at the genome-wide level. Laboratory projects have relevance to radiobiology, radiation biodosimetry, toxicogenomics, photobiology, molecular targets for cancer therapeutics, as well as molecular signaling pathway elucidation and dissection.

Publications

• Bulavin DV, Phillips C, Nannenga B, Timofeev O, Donehower LA, Anderson CW, Appella E, Fornace AJ.Inactivation of the Wip1 phosphatase inhibits mammary tumorigenesis through p38 MAPK-mediated activation of the p16(Ink4a)-p19(Arf) pathway.Nat Genet 2004 Apr
  14991053