Curtis D. Eckhert, Ph.D.
ceckhert@ucla.edu

Dr. Eckhert received his Ph.D. in nutrition and biochemistry from Cornell University (1974) working on the neurochemistry of behavioral changes due to malnutrition. Thereafter he conducted postdoctoral research in neurochemistry (Cornell), trace element metabolism (UC Davis) and visual biochemistry (Stanford). He joined the faculty of UCLA in 1979 where he has worked on projects involving the toxicology and beneficial effects of selenium, riboflavin and boron. He was head of the Division of Nutrition in the School of Public Health from 1987 to 1992, Vice-Chair of the Department of Environmental Health Sciences from 1995-1997 and Chair from 1998 to 2007. Dr. Eckhert is the Associate Director of the UCLA Jonsson Cancer Center’s Molecular Epidemiology Program and Co-PI of the Lead Campus Program in Nanotoxicology in the California NanoSystems Institute funded by the UC Toxic Substances, Research and Training Program.

Research Interests

The principal focus of the Eckhert lab is to elucidate the biology of boron (B) and its relationship to health and disease. B atoms are structural components of RG-II a complex plant polysaccharide. Boron esters bridge chains of RG-II enabling cells to withstand high hydostatic pressures that accompany the elongation of cells during growth. B is thus a natural constituent of fruits, vegetables, nuts and their by-products such as coffee and wine. The dietary consumption of boron by adults in the U.S. ranges from 0.75 to 1.35 mg/day B, values lower than many other countries. Diets rich in B are associated with normal growth and reduced risk of prostate cancer. Boron's growth promoting ability in animal embryos was first identified in rainbow trout in the Eckhert laboratory (FASEB J, 1998) and subsequently shown to be essential during the initial stages of cell cleavage following fertilization of zebrafish eggs (J Exp Biol, 1999). In 2001, Dr. Eckhert and colleagues identified a dose dependent relationship between low dietary intakes of B and the risk of prostate cancer (FASEB J, 2001; Oncology Reports, 2004). The biological plausibility of this was confirmed in human prostate cells (Cancer Letters, 2004). The protective effect of B exposure from diet was confirmed in an ecological study that mapped incidence and mortality Cancer Registry data on groundwater B levels across the state of Texas (Cancer, Causes & Control, 2007). Investigators at the NIEHS also determined that boric acid in drinking water inhibited the growth of human prostate tumors transplanted into nude mice and decreased the level of PSA, a clinical indicator of prostate cancer risk.

The aims of the Eckhert laboratory are to: (1) characterize complexes formed between the form of B circulating in human blood plasma, boric acid, and biomolecules; (2) localize sites of B within cells and tissues; and (3) determine how B inhibits cell proliferation without causing cell death. Mass spectrometry studies showed that boric acid and borate bind to both ribose moieties of nicotinic adenine dinucleotide (NAD+) leading to the formation of several isoforms (J Mass Spectrometry, 2003, 2004). Collaboration with colleagues at LLNL has enabled us to image B within cells using NanoSIMS ion microscopy. The mechanism of the B anti-proliferative effect is being investigated using confocal Ca2+ imaging of live cells, enzymology, and proteomics. Ca2+ imaging studies demonstrated that boric acid inhibits the release of intracellular Ca2+ stores and kinetic studies determined that B inhibits ADP ribosyl cyclase activity (J Chromatography A, 2006). Current work is investigating the impact of B on other key protein complexes of the NAD+/cADPR calcium signaling pathway.

Selected Publications

Henderson K and Eckhert CD. The Effect of Boron on the UPR in Prostate Cancer Cells is Biphasic, FASEB J, Submitted

Barranco WT, Hudak PF and Eckhert CD. Evaluation of ecological and in vitro effects of boron on prostate cancer risk. Cancer Causes Control, 2007

Eckhert CD, Barranco WT, Kim DH. Boron in Animals and Humans: Prostate cancer a model for understanding boron biology. In: Advances in Plant and Animal Boron Nutrition. Fangsen X (ed). Springer-Verlag, 2007.

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 and Eckhert CD. Cellular changes in boric acid-treated DU-145 prostate cancer cells. Brit J. Cancer 94:884-890, 2006.

Henderson K and Eckhert CD. Boric acid induces ER stress in DU-145 and LNCAP prostate cancer cell lines. Soc. Tox. 2006.

Barranco WT and Eckhert CD. Inhibition of DU-145 Prostate Cancer Cell Proliferation by Boron and Selenium is Additive. FASEB J. 2005.

Eckhert, CD. Other Trace Elements. In: Shils ME, Ross AC, Shike M, Caballero B, Cousins RJ. ed. Modern Nutrition in Health and Disease. 10th ed. Baltimore: Williams & Wilkin, 2005.

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, W.T. Eckhert, C.D. Boric acid acts as a cADPR / RyR antagonist during inhibition of human prostate cancer cell proliferation. FASEB J. 18:A351.2 (352.2), 2004.

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.

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.

Classes:

EHS 100
EHS 201

Current Doctoral Students:

Kim Henderson
Sarah Kobylenski
Sergio Huidor