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James D. Yager, Jr., Ph.D.

Photo of Dr. James D. Yager, Jr., Ph.D.

Joint Appointment in Oncology

Background

Titles

  • Joint Appointment in Oncology

Research & Publications

Research Summary

Dr. Yager’s research is focused on investigation of the mechanisms of estrogen carcinogenesis. Oxidative metabolism of estradiol/estrone (E2/E1) leads to formation of E2/E1-catechols then E2/E1-quinones, which form depurinating adducts with adenine and quanine. These adducts can be detected in urine and blood and thus represent biomarkers for E2/E1-induced DNA damage. The guiding hypothesis is that the E2/E1-quinone A and G adducts are causally associated with the initiation and progression of sporadic breast cancer and that reduction in adduct levels will be associated with reduced mammary tumor incidence. Currently, in collaboration with John Groopman, Kala Visvanathan and Tom Kensler we are investigating whether E2/E1-quinone A and G adducts are causally related to the formation of E2-induced mammary tumors in female ACI rats and whether the chemopreventive intervention with sulforaphane reduces mammary tumor incidence in association with reduced adduct levels. Methods are also being developed to measure adduct levels in mammary tissue. The intent is to translate the preclinical studies to clinical trials to investigate whether sulforaphane treatment can reduce E2/E1-quinone A and G adduct levels in women at high risk for developing breast cancer.

Selected Publications

  1. McAtee, B.L.; Yager, J.D. Manganese superoxide dismutase: effect of the ala16val polymorphism on protein, activity, and mRNA levels in human breast cancer cell lines and stably transfected mouse embryonic fibroblasts. Mol Cell Biochem. 2010 Feb;335(1-2):107-118.
  2. Zang, Y.; Odwin-Dacosta, S.; Yager, J.D. Effects of cadmium on estrogen receptor mediated signaling and estrogen induced DNA synthesis in T47D human breast cancer cells. Toxicology letters. 2009 Jan 30;184(2):134-138.
  3. Ramaswamy, V.; Horton, J.; Vandermeer, B.; Buscemi, N.; Miller, S.; Yager, J. Systematic review of biomarkers of brain injury in term neonatal encephalopathy. Pediatr Neurol. 2009 Mar;40(3):215-226.
  4. McAtee, B.L.; Yager, J.D. Manganese superoxide dismutase: effect of the ala16val polymorphism on protein, activity, and mRNA levels in human breast cancer cell lines and stably transfected mouse embryonic fibroblasts. Mol Cell Biochem. 2009 Sep 13.
  5. Chen, J.Q.; Cammarata, P.R.; Baines, C.P.; Yager, J.D. Regulation of mitochondrial respiratory chain biogenesis by estrogens/estrogen receptors and physiological, pathological and pharmacological implications. Biochim Biophys Acta. 2009 Oct;1793(10):1540-1570.
  6. Doyle, A.E.; Yager, J.D. Catechol-O-methyltransferase: Effects of the val108met polymorphism on protein turnover in human cells. Biochim Biophys Acta. 2008 Jan;1780(1):27-33.
  7. Chen, J.Q.; Brown, T.R.; Yager, J.D. Mechanisms of hormone carcinogenesis: evolution of views, role of mitochondria. Advances in experimental medicine and biology. 2008 July 2008;630:1-18.
  8. Bransfield, L.A.; Rennie, A.; Visvanathan, K.; Odwin, S.A.; Kensler, T.W.; Yager, J.D.; Friesen, M.D.; Groopman, J.D. Formation of two novel estrogen guanine adducts and HPLC/MS detection of 4-hydroxyestradiol-N7-guanine in human urine. Chemical research in toxicology. 2008 Aug;21(8):1622-1630.
  9. Yager, J.D.; Chen, J.Q. Mitochondrial estrogen receptors--new insights into specific functions. Trends in endocrinology and metabolism: TEM. 2007 Apr;18(3):89-91.
  10. Watson, W.H.; Yager, J.D. Arsenic: extension of its endocrine disruption potential to interference with estrogen receptor-mediated signaling. Toxicol Sci. 2007 Jul;98(1):1-4.
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