Fornace Laboratories

Cells are subject to numerous forms of stress, everything from ionizing radiation to sunburn to a myriad of chemical agents. When such injuries occur, protective cellular mechanisms are activated. The Fornace laboratory focuses on mammalian stress responses and the complex network of signaling events that can occur after stress. Research in our laboratory has included discovery of the gadd gene group of growth-arrest and DNA-damage inducible genes including GADD45A which was the first p53-regulated stress gene to be identified, and elucidation of some of the signaling pathways involved in cell cycle control, tumor suppression, and apoptosis. Our laboratory also demonstrated a connection between the p53 pathway and p38 MAP kinase signaling. These pathways are important components of the complex network comprising tumor suppressor and stress-response proteins, which maintain homeostasis and which are dysfunctional in cancer. The laboratory has contributed to our understanding of the key roles for these and other stress-signaling pathways in cancer prevention, as well as their perturbations that contribute to tumor development. The Fornace group has pioneered the use of transcriptomics, and more recently metabolomics approaches, for stress signaling applications with relevance to molecular toxicology, oncology, radiobiology, and other injury responses. System biology approaches have been and are continuing to be developed to study signal transduction and perturbations by injury and disease. By understanding genome-wide response to stresses like radiation and chemical toxicants, an important goal is to develop human biomarkers for exposure and disease.

There are currently several areas of active research in the laboratory. In regards to cancer research, a major effort is to understand the effects of radiation, particularly space radiation, on development of gastrointestinal cancer. Much of these studies are supported by a NASA Specialized Center of Research (NSCOR) led by Dr. Fornace. The effect of estrogen mimics (endocrine disruptors) are being studied with a systems biology approach in a multi-institutional program supported by NIEHS; this and related studies have relevance to breast cancer. An ongoing area of interest is the roles for p38 MAP kinase signaling after stresses such as ionizing radiation and ultraviolet radiation. This includes studies on the Wip1 phosphatase which can function as an oncogene by blocking a variety of tumor suppressor pathways including p53, p38 MAP kinase, ATM, and others. Wip1 studies include its roles in gastrointestinal and skin cancer. Another general area of research is the use of metabolomics and other systems approaches to assess the injury responses to stresses such as ionizing radiation and chemical agents. With support from the NIAID Centers for Medical Countermeasures Against Radiation (CMCR), our laboratory is part of a multi-institutional program  to develop biomarkers for radiation exposures, such as would occur during a radiologic and nuclear event.