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|Environmental Health Sciences||Emeriti|
Dr. Eckhert is a world expert on dietary trace elements with a main focus on boron. Boron was discovered to be essential for plants for nearly 70 years before researchers were able to isolate its effects from other nutrients in animal diets and the Institute of Medicine listed it as beneficial for humans. Dr. Eckhert performed a critical study in this effort showing that boron was essential for the cleavage of a zebrafish fertilized egg (zygote) into two and then four cells. This occurs before the onset of embryonic gene expression and proved boron was essential to moving from one generation to another. His laboratory then developed procedures to deplete boron in yeast and mammalian cells setting up conditions to learn what boric acid (BA), the form present in physiological fluids, was doing at the molecular cell level. To identify a dietary boron responsive health effect in humans Dr. Eckhert collaborated with Dr. Zhang, a cancer epidemiologist. Using the methods of epidemiology as a screening tool they found dietary boron was associated with a reduced risk of prostate cancer in a dose dependent manner. A similar reduction in risk was shown across a boron groundwater gradient in Texas providing support for the hypothesis that boron was chemopreventative. These observations stimulated others into the field and boron was quickly shown to be protective against cervical dysplasia, lung cancer and enlargement of the prostate. The Eckhert lab’s approach to identify the underlying mechanism of boron chemoprevention used mass spectrometry to identify and characterize molecular targets of BA, confocal imaging to identify functional molecular targets in live cells, and molecular biological techniques to tease out the downstream molecular pathways leading to cancer prevention. His lab demonstrated cyclic ADP ribose (cADPR) binds boric acid and physiological concentrations BA act as a reversible competitive inhibitor of cADPR function the only known endogenous agonist of the ER ryanodine receptor Ca2+ channel. Boric acid treatment lowers Ca2+ stores in the endoplasmic reticulum (ER) which serves as an intracellular signal that causes changes in mRNA expression and gene products to protect the cell from stress. The effect is rapid and measurable after only 15 minutes post-treatment which is consistent with the rapid response observed in the early zebrafish studies. These studies have provided a proof of the principal that changes in BA levels in serum that can be achieved by diet are sufficient to activate molecular pathways involved in protecting cells from environments stress.
Dr. Eckhert received his Ph.D. in biochemistry and nutrition from Cornell University (1974). Thereafter he conducted postdoctoral research in neurochemistry (Cornell), trace element metabolism (UC Davis) and visual biochemistry (Stanford). He is a former head of the Division of Nutrition and Chair of the Department of Environmental Health Sciences in the FSPH.
Eckhert, C. D. Boron Stimulates Embryonic Trout Growth. J. Nutrition 128:2488-2493, 1998.
Rowe, I. R., Bouzan, C., Nabili, S. and Eckhert, C.D. The response of trout and zebrafish embryos to low and high boron concentrations is U shaped. Biol. Trace Elem. Res. 66:262-270, 1998.
Rowe, R. I. Boron is required for zebrafish embryogenesis. J. Exp. Biol. 202:1649-1654, 1999.
Eckhert, C. D. and Rowe, R. I. Embryonic Dysplasia and Adult Retinal Dystrophy in Boron Deficient Zebrafish. J. Trace Elements Exp. Med. 12: 1999.
Bennett, A., Rowe, R. I., Soch, N. and Eckhert, C. D. boron stimulates yeast (Saccharomyces cerevisiae) growth. J. Nutr.129:2236-2238, 1999.
Kim D. H. S., Marbois B. N., Faull K. F., Eckhert C. D. Esterification of Borate with NAD+ and NADH as Studied by Electrospray Ionization Mass Spectrometry and 11B NMR Spectroscopy. J. Mass Spectrometry 38:632-640, 2003.
Cui Y. Winton M.I., Zhang, Z.F, Rainey C., Marshall J., deKernion J. B., Eckhert, C.D. Dietary Boron Intake and Reduced Risk of Prostate Cancer. Oncology Reports 11:887-892, 2004.
Barranco W.T. and Eckhert C.D. Boric acid inhibits human prostate cancer cell proliferation. Cancer Letters 216:21-29, 2004.
Kim D. H. S., Faull K. F., Norris A. J., Eckhert C. D. Borate-nucleotide complex formation depends on charge and phosphorylation state. J. Mass Spectrometry 39:743-751, 2004.
Barranco WT and Eckhert CD. Cellular changes in boric acid-treated DU-145 prostate cancer cells. Brit J. Cancer 94:884-890, 2006.
Kim DH, Que Hee S, Norris A, Faull KF and Eckhert CD. Boric acid inhibits ADP-ribosyl cyclase non-competitively. J. Chromatography A. 1115:246-252, 2006.
Barranco WT, Hudak PF and Eckhert CD. Evaluation of ecological and in vitro effects of boron on prostate cancer risk; Publisher Erratum Figure 1. Cancer Causes Control.18:71-77, 2007. Publisher Erratum Figure 1. Cancer Causes Control.18:583-584, 2007.
Barranco WT, Kim DH, Stella SL, Eckhert CD. Boric acid inhibits the NAD+/CD38/cADPR Calcium Signaling Pathway. Cell Biol Toxicol DOI 10.1007/s10565-008-9085-7 (Published Online April 2008).
Henderson K, Stella SL Jr, Kobylewski S, Eckhert CD (2009) Receptor Activated Ca2+ Release Is Inhibited by Boric Acid in Prostate Cancer Cells. PLoS ONE 4(6): e6009. doi:10.1371/journal.pone.0006009
Eckhert CD. Trace Elements. In: Ross, A.C., Caballero, B, Cousins, R. J. Tucker, K. L. Ziegler, T. R. ed. Modern Nutrition in Health and Disease. 11th ed. Baltimore: Williams & Wilkin, 2012.
Kim, D, Eckhert, CD, Faull, K. Utilization of Negative Ion ESI-MS and Tandem Mass Spectrometry To Detect and Confirm the NADH-Boric Acid Complex. Journal of Chemical Education 88:106-110, 2011. DOI 10.1021/ed100489g
Henderson, K.A., Kobylewski, S. E., Yamada, K. E. and Eckhert, C. D. Boric acid induces cytoplasmic stress granule formation, eIF2a phosphorylation and AFT4 in prostate DU-145 cells. Biometals November 2014, DOI 10.1007/s10534-014-9809-5