Our Science – Gius Website

David Gius, M.D., Ph.D.

Radiation Oncology Branch Head, Molecular Radiation Oncology Section Investigator Radiation Oncology Branch, NIH 10 Center Drive, MSC 1682 Bldg 10/CRC/Room B2-3561 Bethesda, MD 20892 Phone:   301-496-5457 Fax:   301-480-5439 E-Mail:   giusd@mail.nih.gov

Biography

Dr. Gius graduated from the University of Illinois with a B.S in chemistry in 1983, finished his Ph.D. thesis work from the University of Chicago in 1989, and graduated from Loyola Medical School in 1992. He completed an internship year at the University of Chicago and his radiation oncology residency at Washington University School of Medicine, the Mallinckrodt Institute of Radiology. Dr. Gius received an ASTRO Fellowship Award during his postdoctoral training at the Howard Hughes Medical Institute. In addition, he was a faculty member for 4 years in the Section of Cancer Biology and the Radiation Oncology Department at the Mallinckrodt Institute of Radiology prior to his current position at the NCI.

Research

Molecular Radiation Oncology Section
The laboratory has several areas of research interests with a central theme involving the signaling mechanism that tumor cells use to respond to the damaging and/or cytotoxic effect of exogenous agents that induce oxidative stress. This work is built on the general theme that eukaryotic cells have evolved adaptive responses to multiple forms of environmental stress by initiating genetically preprogrammed signaling pathways. These adaptive responses include the activation of cellular machinery involved in DNA repair, cell cycle arrest, apoptosis, gene induction, and lethality. In response to certain environmental stresses, tumor cells activate a class of proto-oncogenes referred to as early response or immediate early genes. These genes, originally characterized in quiescent cells stimulated by the addition of high concentrations of fetal calf serum, encode nuclear transcription factors. Such factors are involved in the transmission of inter- and intracellular information through multiple cellular signal transduction pathways. It is well established that several specific early response genes are activated in response to exogenous agents that induce intracellular stress including several therapeutic modalities such as chemotherapeutic agents, heat, and ionizing radiation (IR). In this regard, these gene products may function in coupled short-term changes in cellular phenotype by modulating the expression of specific target genes involved in cellular defenses to the damaging effects of IR. Hence, activation of these transcription factors and the subsequent expression of their target genes provide an ideal model system to study the cellular molecular and biochemical events of how tumor and normal eukaryotic cells respond to therapeutic agents including IR.

The overall direction of the laboratory is to investigate the signaling factors/pathways and the downstream transcription factors that are activated in response to IR and determine the physiological consequences of these processes. This is of importance since a greater understanding of the cellular mechanism protecting tumor cells from the cytotoxic effects of IR is a necessary starting point to developing new modalities and agents that could potentially inhibit these protective responses. The laboratory has recently shown that IR and several other cytotoxic agents that are used as radiation sensitizing agents activate several of the same signal transduction pathways and downstream transcription factors through stress-induced alternations in oxidation/reduction (redox) status of these factors. These redox-sensitive signaling proteins that are activated by various other agents that induce cellular oxidative stress appear to transduce signals via critical cysteine residues located in the enzymatic regions of these protein(s). As such, these redox-sensitive signaling cascades may represent a common mechanism that tumor cells use to initiate preprogrammed protective responses to the damaging effects of oxidative agents, including heat and/or IR. Thus, these redox-sensitive signaling cascades may provide a starting point to investigate the protective cellular mechanisms responding to the damaging effects of cytotoxic agents and/or IR.

This page was last updated on 6/11/2008.