Annual scientific retreat: predisposing factors in the development of complex diseases.The 2004 NIEHS Division of Extramural Research and Training's annual scientific retreat was titled "Predisposing Factors in the Development of Complex Diseases." The retreat focused on factors related to aging, immunology, infection, and genetics in the context of understanding risk modulators of environmentally induced diseases. In the first session, participants discussed environmental influences on aging, including the contributions of environmental exposures to the development of chronic diseases, as well as new mouse models for aging and the validity of some of the more popular theories of aging in light of recent study results. The role of oxidative stress and accumulated oxidative damage as a factor in the development of chronic diseases was a common thread throughout these presentations. The second session focused on innate immunity, inflammation, and the role of infection as predisposing factors in chronic disease. One presentation examined the role of bacterial load, asthma, and a hypothesized endotoxin switch that results in diametrically di·a·met·ri·cal also di·a·met·ric adj. 1. Of, relating to, or along a diameter. 2. Exactly opposite; contrary. di different effects in response to an antigen, depending on the dose and timing of exposure. Given that endotoxin potentiated the toxicity of several chemicals noted for their idiosyncratic reactions, these responses may have resulted from low-level, episodic, inflammatory events. Finally, data presented in the final talk of the session suggest that undernutrition Undernutrition A type of malnutrition caused by inadequate food intake or the body's inability to make use of needed nutrients. Mentioned in: Appetite-Enhancing Drugs undernutrition see malnutrition, starvation. in a host organism plays an important role in the rapid evolution of infectious agents including influenza viruses. The final session focused on opportunities and challenges in using population-based studies to investigate gene-environment interactions leading to human disease, including the lack of repeatability of candidate gene association studies. A "unified" approach that assembles overlapping and synergistic networks of pathways for analyses was recommended in place of single candidate gene studies. This unified approach relies on data from expression microarrays, proteomics, and siRNA studies to identify genes that may not be part of recognized pathways. All relevant information can be analyzed using a hierarchical modeling approach. One example given demonstrated some of the challenges of using animal models to study human diseases. Data from mouse models used to study atherogenesis atherogenesis /ath·ero·gen·e·sis/ (-jen´e-sis) formation of atheromatous lesions in arterial walls.atherogen´ic ath·er·o·gen·e·sis n. displayed a paradox when considering genotype and phenotype. Contrary to the accepted hypothesis positing downregulation of low-density lipoprotein receptor (LDLR) in humans, expression of the human APOE APOE ε4 Molecular neurology The type 4 allele of the apolipoprotein E gene locus located on chromosome 19, which may↑ the risk of late-onset Alzheimer's disease, and has been associated with ↓ cerebral parietal metabolism; possession of an 4 isoform combined with increased LDLR was harmful in genetically modified mice when red a high-fat Western diet, predicting important interactions between genotype/phenotype and exposure. The topics of this year's retreat offered potential new research directions by demonstrating some of the challenges in identifying predisposing factors in complex diseases. The Division of Extramural Research and Training will consider these issues as it develops strategic plans for enhancing research programs at the NIEHS. Invite Speakers Melinda Beck University of North Carolina--Chapel Hill Robert Floyd Oklahoma Medical Research Foundation The Oklahoma Medical Research Foundation (OMRF), located in Oklahoma City, Oklahoma, is an independent, nonprofit biomedical research institute. Established in 1946, OMRF is dedicated to understanding and developing more effective treatments for human disease. Stephen M. John Groopman The Johns Hopkins University Johns Hopkins University, mainly at Baltimore, Md. Johns Hopkins in 1867 had a group of his associates incorporated as the trustees of a university and a hospital, endowing each with $3.5 million. Daniel C. Howard Hu Harvard School of Public Health The Harvard School of Public Health is (colloquially, HSPH) is one of the professional graduate schools of Harvard University. Located in Longwood Area of the Boston, Massachusetts neighborhood of Mission Hill, next to Harvard Medical School and Cambridge, Massachusetts, Nobuyo Maeda University of North Carolina--Chapel Hill Richard Miller University of Michigan (body, education) University of Michigan - A large cosmopolitan university in the Midwest USA. Over 50000 students are enrolled at the University of Michigan's three campuses. The students come from 50 states and over 100 foreign countries. School of Medicine Robert Roth Michigan State University Michigan State University, at East Lansing; land-grant and state supported; coeducational; chartered 1855. It opened in 1857 as Michigan Agricultural College, the first state agricultural college. Silke Schmidt Duke University Medical Center Duncan Thomas University of Southern California The U.S. News & World Report ranked USC 27th among all universities in the United States in its 2008 ranking of "America's Best Colleges", also designating it as one of the "most selective universities" for admitting 8,634 of the almost 34,000 who applied for freshman admission Holly Van Remmen The University of Texas Health Science Center at San Antonio Donata Vercelli The University of Arizona |
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