The bioAMS facility at LLNL supports research across a broad range of biomedical applications, supporting users as they tackle challenges such as environmental toxins and carcinogens, therapeutic microdosing, personalized medicine, and the pharmacokinetics of new drug candidates.
Explore this page to learn more about research conducted by users who incorporated bioAMS analytical capabilities into their investigations as well as research aimed at enhancing our capabilities to better serve our user community.
Environmental toxins and contaminants
Studying the response of biological systems after exposure to toxins and carcinogens
Pande P, Madeen EP, Williams DE, Crowell SR, Ognibene TJ, Turteltaub KW, Corley RA, Smith JN. Translating dosimetry of Dibenzo[def,p]chrysene (DBC) and metabolites across dose and species using physiologically based pharmacokinetic (PBPK) modeling. Toxicol Appl Pharmacol. 2022 Mar 1;438:115830. doi: 10.1016/j.taap.2021.115830. Epub 2021 Dec 18. PMID: 34933053; PMCID: PMC9264404.
Carratt SA, Hartog M, Buchholz BA, Kuhn EA, Collette NM, Ding X, Van Winkle LS. Naphthalene genotoxicity: DNA adducts in primate and mouse airway explants. Toxicol Lett. 2019 May 1;305:103-109. Epub 2019 Jan 24. PMID: 30684585; PMCID: PMC6459408.
Enright HA, Falso MJS, Malfatti MA, Lao V, Kuhn EA, Hum N, Shi Y, Sales AP, Haack KW, Kulp KS, Buchholz BA, Loots GG, Bench G, Turteltaub KW. Maternal exposure to an environmentally relevant dose of triclocarban results in perinatal exposure and potential alterations in offspring development in the mouse model. PLoS One. 2017 Aug 9;12(8):e0181996. doi: 10.1371/journal.pone.0181996. PMID: 28792966; PMCID: PMC5549899.
Therapeutic modifications
Therapeutic options for health challenges, including microdosing and cancer research
Bennion BJ, Malfatti MA, Be NA, Enright HA, Hok S, Cadieux CL, Carpenter TS, Lao V, Kuhn EA, McNerney MW, Lightstone FC, Nguyen TH, Valdez CA. Development of a CNS-permeable reactivator for nerve agent exposure: an iterative, multi-disciplinary approach. Sci Rep. 2021 Jul 30;11(1):15567. PMID: 34330964; PMCID: PMC8324913.
Zimmermann M, Li T, Semrad TJ, Wu CY, Yu A, Cimino G, Malfatti M, Haack K, Turteltaub KW, Pan CX, Cho M, Kim EJ, Henderson PT. Oxaliplatin-DNA Adducts as Predictive Biomarkers of FOLFOX Response in Colorectal Cancer: A Potential Treatment Optimization Strategy. Mol Cancer Ther. 2020 Apr;19(4):1070-1079. PMID: 32029633; PMCID: PMC7192311.
Malfatti MA, Kuhn EA, Murugesh DK, Mendez ME, Hum N, Thissen JB, Jaing CJ, Loots GG. Manipulation of the Gut Microbiome Alters Acetaminophen Biodisposition in Mice. Sci Rep. 2020 Mar 12;10(1):4571. PMID: 32165665; PMCID: PMC7067795.
Scharadin TM, Malfatti MA, Haack K, Turteltaub KW, Pan CX, Henderson PT, Jonas BA. Toward Predicting Acute Myeloid Leukemia Patient Response to 7 + 3 Induction Chemotherapy via Diagnostic Microdosing. Chem Res Toxicol. 2018 Oct 15;31(10):1042-1051. doi: 10.1021/acs.chemrestox.8b00107. Epub 2018 Sep 10. PMID: 30152692; PMCID: PMC6387632.
Zimmermann M, Wang SS, Zhang H, Lin TY, Malfatti M, Haack K, Ognibene T, Yang H, Airhart S, Turteltaub KW, Cimino GD, Tepper CG, Drakaki A, Chamie K, de Vere White R, Pan CX, Henderson PT. Microdose-Induced Drug-DNA Adducts as Biomarkers of Chemotherapy Resistance in Humans and Mice. Mol Cancer Ther. 2017 Feb;16(2):376-387. doi: 10.1158/1535-7163.MCT-16-0381. Epub 2016 Nov 30. PMID: 27903751; PMCID: PMC5335870.
Scharadin TM, Zhang H, Zimmermann M, Wang S, Malfatti MA, Cimino GD, Turteltaub K, de Vere White R, Pan CX, Henderson PT. Diagnostic Microdosing Approach to Study Gemcitabine Resistance. Chem Res Toxicol. 2016 Nov 21;29(11):1843-1848. doi: 10.1021/acs.chemrestox.6b00247. Epub 2016 Oct 10. PMID: 27657672; PMCID: PMC5385140.
Cai H, Scott E, Kholghi A, Andreadi C, Rufini A, Karmokar A, Britton RG, Horner-Glister E, Greaves P, Jawad D, James M, Howells L, Ognibene T, Malfatti M, Goldring C, Kitteringham N, Walsh J, Viskaduraki M, West K, Miller A, Hemingway D, Steward WP, Gescher AJ, Brown K. Cancer chemoprevention: Evidence of a nonlinear dose response for the protective effects of resveratrol in humans and mice. Sci Transl Med. 2015 Jul 29;7(298):298ra117. doi: 10.1126/scitranslmed.aaa7619. PMID: 26223300; PMCID: PMC4827609.
Pharmacokinetics and metabolic pathway analysis
Tracking how compounds are absorbed, distributed, metabolized, and eliminated
Chuang JC, Clifford AJ, Kim SH, Novotny JA, Kelly PB, Holstege DM, Walzem RL. Separation of Lipoproteins for Quantitative Analysis of 14C-Labeled Lipid-Soluble Compounds by Accelerator Mass Spectrometry. Int J Mol Sci. 2024 Feb 3;25(3):1856. PMID: 38339135; PMCID: PMC10855872.
Vermillion Maier ML, Siddens LK, Pennington JM, Uesugi SL, Tilton SC, Vertel EA, Anderson KA, Tidwell LG, Ognibene TJ, Turteltaub KW, Smith JN, Williams DE. Benzo[a]pyrene toxicokinetics in humans following dietary supplementation with 3,3'-diindolylmethane (DIM) or Brussels sprouts. Toxicol Appl Pharmacol. 2023 Feb 1;460:116377. PMID: 36642108; PMCID: PMC9946811.
Vermillion Maier ML, Siddens LK, Pennington JM, Uesugi SL, Anderson KA, Tidwell LG, Tilton SC, Ognibene TJ, Turteltaub KW, Smith JN, Williams DE. Benzo[a]pyrene (BaP) metabolites predominant in human plasma following escalating oral micro-dosing with [14C]-BaP. Environ Int. 2022 Jan 15;159:107045. doi: 10.1016/j.envint.2021.107045. Epub 2021 Dec 15. PMID: 34920278; PMCID: PMC8791557.
Buchholz BA, Ahn KC, Huang H, Gee SJ, Stewart BJ, Ognibene TJ, Hammock BD. Pharmacokinetics, Metabolite Measurement, and Biomarker Identification of Dermal Exposure to Permethrin Using Accelerator Mass Spectrometry. Toxicol Sci. 2021 Aug 30;183(1):49-59. doi: 10.1093/toxsci/kfab082. PMID: 34460930; PMCID: PMC8404990.
Garrod MG, Rossow HA, Calvert CC, Miller JW, Green R, Buchholz BA, Allen LH. 14C-Cobalamin Absorption from Endogenously Labeled Chicken Eggs Assessed in Humans Using Accelerator Mass Spectrometry. Nutrients. 2019 Sep 8;11(9):2148. PMID: 31500393; PMCID: PMC6769442.
Bomb-pulse biology
Using variations in the environmental levels of carbon-14 to examine cellular and macromolecular turnover
Hackenberg KAM, Rajabzadeh-Oghaz H, Dreier R, Buchholz BA, Navid A, Rocke DM, Abdulazim A, Hänggi D, Siddiqui A, Macdonald RL, Meng H, Etminan N. Collagen Turnover in Relation to Risk Factors and Hemodynamics in Human Intracranial Aneurysms. Stroke. 2020 May;51(5):1624-1628. Erratum in: Stroke. 2020 May;51(5):e102. PMID: 32192404; PMCID: PMC7340076.
Stewart DN, Lango J, Nambiar KP, Falso MJ, FitzGerald PG, Rocke DM, Hammock BD, Buchholz BA. Carbon turnover in the water-soluble protein of the adult human lens. Mol Vis. 2013;19:463-75. Epub 2013 Feb 25. PMID: 23441119; PMCID: PMC3580966.
Spalding KL, Bergmann O, Alkass K, Bernard S, Salehpour M, Huttner HB, Boström E, Westerlund I, Vial C, Buchholz BA, Possnert G, Mash DC, Druid H, Frisén J. Dynamics of hippocampal neurogenesis in adult humans. Cell. 2013 Jun 6;153(6):1219-1227. doi: 10.1016/j.cell.2013.05.002. PMID: 23746839; PMCID: PMC4394608.
Bergmann O, Bhardwaj RD, Bernard S, Zdunek S, Barnabé-Heider F, Walsh S, Zupicich J, Alkass K, Buchholz BA, Druid H, Jovinge S, Frisén J. Evidence for cardiomyocyte renewal in humans. Science. 2009 Apr 3;324(5923):98-102. doi: 10.1126/science.1164680. PMID: 19342590; PMCID: PMC2991140.
Spalding KL, Bhardwaj RD, Buchholz BA, Druid H, Frisén J. Retrospective birth dating of cells in humans. Cell. 2005 Jul 15;122(1):133-43. doi: 10.1016/j.cell.2005.04.028. PMID: 16009139.
Lovell MA, Robertson JD, Buchholz BA, Xie C, Markesbery WR. Use of bomb pulse carbon-14 to age senile plaques and neurofibrillary tangles in Alzheimer's disease. Neurobiol Aging. 2002 Mar-Apr;23(2):179-86. doi: 10.1016/s0197-4580(01)00281-0. PMID: 11804701.
Biomedical AMS instrumentation and technology
Enhancing our capabilities to better serve our user community
Jiang J, McCartt AD. Mid-infrared trace detection with parts-per-quadrillion quantitation accuracy: Expanding frontiers of radiocarbon sensing. Proc Natl Acad Sci U S A. 2024 Apr 9;121(15):e2314441121. doi: 10.1073/pnas.2314441121. Epub 2024 Mar 21. PMID: 38513090; PMCID: PMC11009668.
Jiang J, McCartt AD. Two-color, intracavity pump-probe, cavity ringdown spectroscopy. J Chem Phys. 2021 Sep 14;155(10):104201. Erratum in: J Chem Phys. 2022 Mar 28;156(12):129902. PMID: 34525821; PMCID: PMC8428946.
McCartt AD, Jiang J. Room-Temperature Optical Detection of 14CO2 below the Natural Abundance with Two-Color Cavity Ring-Down Spectroscopy. ACS Sens. 2022 Nov 25;7(11):3258-3264. PMID: 36315969; PMCID: PMC10289126.
Baliu-Rodriguez D, Stewart BJ, Ognibene TJ. HPLC-Parallel accelerator and molecular mass spectrometry analysis of 14C-labeled amino acids. J Chromatogr B Analyt Technol Biomed Life Sci. 2023 Feb 1;1216:123590. PMID: 36669256; PMCID: PMC9994536.
Stewart BJ, Ognibene TJ. Parallel Accelerator and Molecular Mass Spectrometry Measurement of Carbon-14-Labeled Analytes. Methods Mol Biol. 2022;2349:1-10. PMID: 34718988; PMCID: PMC10868718.
Thomas AT, Stewart BJ, Ognibene TJ, Turteltaub KW, Bench G. Directly coupled high-performance liquid chromatography-accelerator mass spectrometry measurement of chemically modified protein and peptides. Anal Chem. 2013 Apr 2;85(7):3644-50. doi: 10.1021/ac303609n. Epub 2013 Mar 20. PMID: 23413773; PMCID: PMC4034139.
Ognibene TJ, Bench G, Vogel JS, Peaslee GF, Murov S. A high-throughput method for the conversion of CO2 obtained from biochemical samples to graphite in septa-sealed vials for quantification of 14C via accelerator mass spectrometry. Anal Chem. 2003 May 1;75(9):2192-6. PMID: 12720362.
