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Intramural Research Accomplishments 2006

June 2007

In its March-April 2007 issue (http://www.nih.gov/catalyst/2007/07.03.01/page4.html , the editors of the NIH Catalyst listed brief summaries of intramural research accomplishments from the NIH institutes and centers. In the areas that fit the Institute's research agenda and mission, NIEHS researchers were disproportionately well represented. Numbers in parentheses refer to how many NIEHS studies and how many total studies were recognized in each category.

Identification of Disease Genes (2 of 5)

• Identification of the K55R polymorphism variant allele in association with increased risk of coronary heart disease in Caucasians in a community-based study of atherosclerosis risk, implicating EPHX2 as a potential cardiovascular disease-susceptibility gene -
  • Lee CR, North KE, Bray MS, Fornage M, Seubert JM, Newman JW, Hammock BD, Couper DJ, Heiss G, Zeldin DC(http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=Abstract&list_uids=16595607&query_hl=10&itool=pubmed_docsum . 2006. Genetic variation in soluble epoxide hydrolase (EPHX2) and risk of coronary heart disease: an Atherosclerosis Risk in Communities (ARIC) study. Hum Mol Genet 15:1640-1649.
• Single mutations in the human master regulator p53 found to dramatically alter cellular response to environmental stress, potentially exerting an effect on tumor development and therapeutic efficacy
  • Menendez D, Inga A, Resnick MA(http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=Abstract&list_uids=16508005&query_hl=11&itool=pubmed_docsum . 2006. The biological impact of the human master regulator p53 can be altered by mutations that change the spectrum and expression of its target genes. Mol Cell Biol 26:2297-2308.

Basic Discoveries in Cell, Molecular, and Structural Biology with Implications for the Treatment of Human Disease (3 of 56)

• Discovery of a new molecular mechanism for thyroid hormone action, providing new insight into the role of thyroid hormone in human brain, heart, lipid and neuronal matters and underscoring concerns about agricultural chemicals that interfere with thyroid hormone activities and such public-health problems as learning disorders, cardiovascular disease, obesity and depression -
  • Storey NM, Gentile S, Ullah H, Russo A, Muessel M, Erxleben C, Armstrong DL(http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=Abstract&list_uids=16549781&query_hl=12&itool=pubmed_docsum . 2006. Rapid signaling at the plasma membrane by a nuclear receptor for thyroid hormone. Proc Natl Acad Sci USA 103:5197-5201.
• Structural analysis of DNA strand slippage that generates deleterious mutations underlying disease, supporting a decades-old but previously unproven idea -
  • Garcia-Diaz M, Bebenek K, Krahn JM, Pedersen LC, Kunkel TA(http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=Abstract&list_uids=16439207&query_hl=2&itool=pubmed_docsum . 2006. Structural analysis of strand misalignment during DNA synthesis by a human DNA polymerase. Cell 124:331-342.
• TLR4 gene found to protect against tumor development in mice, suggesting that targeting the innate immune system may be useful in fighting human diseases, including cancer -
  • Bauer AK, Dixon D, DeGraff LM, Cho H-Y, Walker CR, Malkinson AM, Kleeberger SR(http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=Abstract&list_uids=16333033&query_hl=14&itool=pubmed_docsum . 2005. Toll-Like Receptor 4 in Butylated Hydroxytoluene-Induced Mouse Pulmonary Inflammation and Tumorigenesis. J Natl Cancer Inst 97:1778-1781.

Development of New or Improved Approaches for Preventing or Delaying the Onset or Progression of Disease and Disability (1 of 16)

• Finding that overweight and obese men have decreased fertility, with a 20-pound increase yielding a ten percent increase in infertility risk -
  • Sallmen M, Sandler DP, Hoppin JA, Blair A, Baird DD(http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=Abstract&list_uids=16837825&query_hl=8&itool=pubmed_docsum . 2006. Evidence for reduced fertility among overweight and obese men. Epidemiology 17(5):520-523.

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