Brian Thrall manages PNNL’s biological research sectors, which include major biomedical and environmental biology research programs sponsored by the National Institutes of Health (NIH) and the U.S. Department of Energy. For over 15 years, he has also served as principal investigator for NIH-funded research programs focused on the interactions between particulates, engineered nanomaterials, and biological systems. He regularly serves in an advisory role and reviewer for NIH and other federal sponsors in the area of proteomic and genomic analysis of the health effects of environmental agents.
Thrall's laboratory currently focuses on understanding the mechanisms in which engineered nanomaterials interact with cells and tissues. Using macrophages and a variety of epithelial cell types as model systems, his research employs genomic, proteomic, and cellular imaging approaches, coupled with computational biology strategies to identify the pathways modulated by nanoparticles and the implications of these pathways for human health. The goal of these studies is to identify fundamental principles which dictate biocompatibility of nanomaterials in order to guide safe and effective applications of these technologies.
Disciplines and Skills
- Modulation of cell signaling pathways by environmental agents
- PhD in Pharmacology, Washington State University
- MA in Biology, University of South Dakota
- BS in Biology, University of South Dakota
Affiliations and Professional Service
- American Society for Cell Biology
- Society of Toxicology, Molecular Biology Specialty Section
- Pacific Northwest Association of Toxicologist
- American Association for the Advancement of Science
- Cao X., T. Zhang, G.M. DeLoid, M.J. Gaffrey, K.K. Weitz, B.D. Thrall, and W. Qian, et al. 2020. "Evaluation of the cytotoxic and cellular proteome impacts of food-grade TiO2 (E171) using simulated gastrointestinal digestions and a tri-culture small intestinal epithelial model." NanoImpact 17:100202. PNNL-SA-147195. doi:10.1016/j.impact.2019.100202
- Khare S., G.M. Deloid, R.M. Molina, K. Gokulan, S.P. Couvillion, K.J. Bloodsworth, and E.K. Eder, et al. 2020. "Effects of ingested nanocellulose on intestinal microbiota and homeostasis in Wistar Han rats." NanoImpact 18:100216. PNNL-SA-149247. doi:10.1016/j.impact.2020.100216
- Thrall B.D., V.K. Kodali, S.J. Skerret, S.J. Skerret, D.G. Thomas, C. Frevert, and J.G. Pounds, et al. 2019. "Modulation of susceptibility to lung bacterial infection by engineered nanomaterials: In vitro and in vivo correspondence based on macrophage phagocytic function." NanoImpact 14:100155. PNNL-SA-128523. doi:10.1016/j.impact.2019.100155
- Whidbey C., N.C. Sadler, R.N. Nair, R.F. Volk, A.J. DeLeon, L.M. Bramer, and S.J. Fansler, et al. 2019. "A Probe-Enabled Approach for the Selective Isolation and Characterization of Functionally Active Subpopulations in the Gut Microbiome." Journal of the American Chemical Society 141, no. 1:42-47. PNNL-SA-127532. doi:10.1021/jacs.8b09668
- Smith J.N., D.G. Thomas, H.D. Jolley, V.K. Kodali, M.H. Littke, P. Munusamy, and D.R. Baer, et al. 2018. "All that is Silver is not Toxic: Silver Ion and Particle Kinetics Reveals the Role of Silver Ion Aging and Dosimetry on the Toxicity of Silver Nanoparticles." Particle and Fibre Toxicology 15:Article No. 47. PNNL-SA-135829. doi:10.1186/s12989-018-0283-z
- Thomas D.G., J.N. Smith, B.D. Thrall, D.R. Baer, H.D. Jolley, P. Munusamy, and V.K. Kodali, et al. 2018. "ISD3: A Particokinetic Model for Predicting the Combined Effects of Particle Sedimentation, Diffusion and Dissolution on Cellular Dosimetry for In Vitro Systems." Particle and Fibre Toxicology 15:Article No. 6. PNNL-SA-125563. doi:10.1186/s12989-018-0243-7
- Shrivastava M.B., S. Lou, A. Zelenyuk-Imre, R.C. Easter, R.A. Corley, B.D. Thrall, and P.J. Rasch, et al. 2017. "Global Long-Range Transport and Lung Cancer Risk from Polycyclic Aromatic Hydrocarbons Shielded by Coatings of Organic Aerosol." Proceedings of the National Academy of Sciences of the United States of America 114, no. 6:1246-1251. PNNL-SA-121554. doi:10.1073/pnas.1618475114
- Baer D.R., P. Munusamy, and B.D. Thrall. 2016. "Provenance information as a tool for addressing engineered nanoparticle reproducibility challenges." Biointerphases 11, no. 4:Article No. 04B401. PNNL-SA-120689. doi:10.1116/1.4964867
- Duan J., V.K. Kodali, M.J. Gaffrey, J. Guo, R.K. Chu, D.G. Camp, and R.D. Smith, et al. 2015. "Quantitative Profiling of Protein S-Glutathionylation Reveals Redox-Dependent Regulation of Macrophage Function During Nanoparticle-Induced Oxidative Stress." ACS Nano 10, no. 1:524-538. PNNL-SA-112721. doi:10.1021/acsnano.5b05524
- Munusamy P., C.M. Wang, M.H. Engelhard, D.R. Baer, J.N. Smith, C. Liu, and V.K. Kodali, et al. 2015. "Comparison of 20 nm silver nanoparticles synthesized with and without a gold core: Structure, dissolution in cell culture media, and biological impact on macrophages." Biointerphases 10, no. 3:031003-1 to 031003-16. PNNL-SA-102846. doi:10.1116/1.4926547
- Su D., M.J. Gaffrey, J. Guo, K.E. Hatchell, R.K. Chu, T.R. Clauss, and J.T. Aldrich, et al. 2014. "Proteomic Identification and Quantification of S-glutathionylation in Mouse Macrophages Using Resin-Assisted Enrichment and Isobaric Labeling." Free Radical Biology & Medicine 67:460-470. PNNL-SA-96702. doi:10.1016/j.freeradbiomed.2013.12.004
- Teeguarden J.G., V.B. Mikheev, K.R. Minard, W.C. Forsythe, W. Wang, G. Sharma, and N.J. Karin, et al. 2014. "Comparative Iron Oxide Nanoparticle Cellular Dosimetry and Response in Mice by the Inhalation and Liquid Cell Culture Exposure Routes." Particle and Fibre Toxicology 11:Article no. 46. PNNL-SA-101188. doi:10.1186/s12989-014-0046-4
- Kodali V.K., M.H. Littke, S.C. Tilton, J.G. Teeguarden, L. Shi, C.W. Frevert, and W. Wang, et al. 2013. "Dysregulation of Macrophage Activation Profiles by Engineered Nanoparticles." ACS Nano 7, no. 8:6997-7010. PNNL-SA-95359. doi:10.1021/nn402145t
- Minard K.R., M.H. Littke, W. Wang, Y. Xiong, J.G. Teeguarden, and B.D. Thrall. 2013. "Magnetic Particle Detection (MPD) for In-Vitro Dosimetry." Biosensors and Bioelectronics 43:88-93. PNNL-SA-90647. doi:10.1016/j.bios.2012.12.011
- Sharma G., V.K. Kodali, M.J. Gaffrey, W. Wang, K.R. Minard, N.J. Karin, and J.G. Teeguarden, et al. 2013. "Iron Oxide Nanoparticle Agglomeration Influences Dose-Rates and Modulates Oxidative Stress Mediated Dose-Response Profiles In Vitro." Nanotoxicology 8, no. 6:663-675. PNNL-SA-93447. doi:10.3109/17435390.2013.822115
- Karakoti A.S., P. Munusamy, K.E. Hostetler, V.K. Kodali, S.N. Kuchibhatla, G. Orr, and J.G. Pounds, et al. 2012. "Preparation and Characterization Challenges to Understanding Environmental and Biological Impacts of Ceria Nanoparticles." Surface and Interface Analysis 44, no. 8:881-889. PNNL-SA-83765. doi:10.1002/sia.5006
- Nielsen C.E., D.A. Wilson, A.L. Brooks, S. McCord, G.E. Dagle, A.C. James, and S.Y. Tolmachev, et al. 2012. "Microdistribution and Long-Term Retention of 239Pu (NO3)4 in the Respiratory Tracts of an Acutely Exposed Plutonium Worker and Experimental Beagle Dogs." Cancer Research 72, no. 21:5529-5536. PNNL-SA-87930. doi:10.1158/0008-5472.CAN-12-1824
- Thrall B.D., K.R. Minard, J.G. Teeguarden, and K.M. Waters. 2012. Multiscale Toxicology - Building the Next Generation Tools for Toxicology. PNNL-21916. Richland, WA: Pacific Northwest National Laboratory.
- Waters K.M., T. Liu, R.D. Quesenberry, A.R. Willse, S. Bandyopadhyay, L.E. Kathmann, and T.J. Weber, et al. 2012. "Network Analysis of Epidermal Growth Factor Signaling using Integrated Genomic, Proteomic and Phosphorylation Data." PLoS One 7, no. 3:Article No. e34515. PNNL-SA-85737. doi:10.1371/journal.pone.0034515
- Baer D.R., A.S. Karakoti, P. Munusamy, B.D. Thrall, J.G. Pounds, J.G. Teeguarden, and J.E. Amonette, et al. 2011. "Testing in EHS: What is the Current Status of Experimentation?." In 11th IEEE International Conference on Nanotechnology (IEEE-NANO 2011), August 15-18, 2011, Portland, Oregon, 18-19. Piscataway, New Jersey:IEEE. PNNL-SA-90027. doi:10.1109/NANO.2011.6144671
- McDermott J.E., M.N. Archuleta, B.D. Thrall, J.N. Adkins, and K.M. Waters. 2011. "Controlling the Response: Predictive Modeling of a Highly Central, Pathogen-Targeted Core Response Module in Macrophage Activation." PLoS One 6, no. 2:e14673. PNWD-SA-9011. doi:10.1371/journal.pone.0014673
- Orr G., W.B. Chrisler, K.J. Cassens, R. Tan, B.J. Tarasevich, L.M. Markillie, and R.C. Zangar, et al. 2011. "Cellular Recognition and Trafficking of Amorphous Silica Nanoparticles by Macrophage Scavenger Receptor A." Nanotoxicology 5, no. 3:296-311. PNNL-SA-68643. doi:10.3109/17435390.2010.513836
- Zhang H., K.E. Burnum, M.L. Luna, B.O. Petritis, J. Kim, W. Qian, and R.J. Moore, et al. 2011. "Quantitative proteomics analysis of adsorbed plasma proteins classifies nanoparticles with different surface properties and size." Proteomics 11, no. 23:4569-4577. PNNL-SA-74159. doi:10.1002/pmic.201100037
- Hinderliter P.M., K.R. Minard, G. Orr, W.B. Chrisler, B.D. Thrall, J.G. Pounds, and J.G. Teeguarden. 2010. "ISDD: A Computational Model of Particle Sedimentation, Diffusion and Target Cell Dosimetry for In Vitro Toxicity Studies." Particle and Fibre Toxicology 7, no. November:Article No. 36. PNNL-SA-74873. doi:10.1186/1743-8977-7-36
- Waters K.M., L.M. Masiello, R.C. Zangar, B.J. Tarasevich, N.J. Karin, R.D. Quesenberry, and S. Bandyopadhyay, et al. 2009. "Macrophage Responses to Silica Nanoparticles are Highly Conserved Across Particle Sizes." Toxicological Sciences 107, no. 2:553-569. PNNL-SA-62659. doi:10.1093/toxsci/kfn250
- Jacobs J.M., K.M. Waters, L.E. Kathmann, D.G. Camp, H.S. Wiley, R.D. Smith, and B.D. Thrall. 2008. "The Mammary Epithelial Cell Secretome and its Regulation by Signal Transduction Pathways." Journal of Proteome Research 7, no. 2:558-569. PNNL-SA-56310. doi:10.1021/pr0704377
- Rogers S., M. Girolami, M. Girolami, W. Kolch, K.M. Waters, T. Liu, and B.D. Thrall, et al. 2008. "Investigating the Correspondence Between Transcriptomic and Proteomic Expression Profiles Using Coupled Cluster Models." Bioinformatics 24, no. 24:2894-2900. PNNL-SA-61286. doi:10.1093/bioinformatics/btn553
- Teeguarden J.G., P.M. Hinderliter, G. Orr, B.D. Thrall, and J.G. Pounds. 2007. "Particokinetics In Vitro: Dosimetry Considerations for In Vitro Nanoparticle Toxicity Assessments." Toxicological Sciences 95, no. 2:300-312. PNNL-SA-55055. doi:10.1093/toxsci/kfl165
- Waters K.M., J.G. Pounds, and B.D. Thrall. 2006. "Data Merging for Integrated Microarray and Proteomic Analysis." Briefings in Functional Genomics and Proteomics 5, no. 4:261-272. PNNL-SA-47947. doi:10.1093/bfgp/ell019
- Weber T.J., H.S. Smallwood, L.E. Kathmann, L.M. Markillie, T.C. Squier, and B.D. Thrall. 2006. "Functional link between TNF biosynthesis and CaM-dependent activation of inducible nitric oxide synthase in RAW 264.7 macrophages." American Journal of Physiology. Cell Physiology 290, no. 6:C1512-C1520. PNNL-SA-47434. doi:10.1152/ajpcell.00527.2005
- Liu T., W. Qian, W.U. Chen, J.M. Jacobs, R.J. Moore, D.J. Anderson, and M.A. Gritsenko, et al. 2005. "Improved Proteome Coverage by Using High Efficiency Cysteinyl-peptide Enrichment: The Human Mammary Epithelial Cell Proteome." Proteomics 5, no. 5:1263-1273. PNNL-SA-42468. doi:10.1002/pmic.200401055
- Sowa M.B., L.E. Kathmann, B.A. Holben, B.D. Thrall, and G.A. Kimmel. 2005. "Low-LET Microbeam Investigation of the Track-End Dependence of Electron-Induced Damage in Normal Human Diploid Fibroblasts." Radiation Research 164, no. 5:677-679. PNNL-SA-42273. doi:10.1667/rr3464.1
- Chen W.U., R.L. Woodbury, L.E. Kathmann, L. Opresko, R.C. Zangar, H.S. Wiley, and B.D. Thrall. 2004. "Induced autocrine signaling through the epidermal growth factor receptor contributes to the response of mammary epithelial cells to tumor necrosis factor alpha." Journal of Biological Chemistry 279, no. 18:18488-18496. PNNL-SA-40802.
- Jacobs J.M., H.M. Mottaz, L. Yu, D.J. Anderson, R.J. Moore, W.U. Chen, and K.J. Auberry, et al. 2004. "Multidimensional Proteome Analysis of Human Mammary Epithelial Cells." Journal of Proteome Research 3, no. 1:68-75. PNWD-SA-6087.
- Liu T., W. Qian, E.F. Strittmatter, D.G. Camp, G.A. Anderson, B.D. Thrall, and R.D. Smith. 2004. "High throughput comparative proteome analysis using a quantitative cysteinyl-peptide enrichment technology." Analytical Chemistry 76, no. 18:5345-5353. PNWD-SA-6477.
- Minard K.R., G.R. Holtom, L.E. Kathmann, P.D. Majors, B.D. Thrall, and R.A. Wind. 2004. "Simultaneous 1H PFG-NMR and Confocal Microscopy of Monolayer Cell Cultures: Effects of Apoptosis and Necrosis on Water Diffusion and Compartmentalization." Magnetic Resonance in Medicine 52, no. 3:495-505. PNNL-SA-40185.
- Weber T.J., S. Negash, H.S. Smallwood, K.S. Ramos, B.D. Thrall, and T.C. Squier. 2004. "Calmodulin Involvement in Stress-Activated Nuclear Localization of Albumin in JB6 Epithelial Cells." Biochemistry 43, no. 23:7443-7450. PNNL-SA-40924.
- Chen W.U., L. Yu, E.F. Strittmatter, B.D. Thrall, D.G. Camp, and R.D. Smith. 2003. "Detection of in situ labeled cell surface proteins by mass spectrometry: application to the membrane subproteome of human mammary epithelial cells." Proteomics 3, no. 8:1647-1651. PNWD-SA-5957.
- Harms G.S., G. Orr, M. Montal, B.D. Thrall, S.D. Colson, and H.P. Lu. 2003. "Probing conformational changes of gramicidin ion channels by single-molecule patch-clamp fluorescence microscopy." Biophysical Journal 85, no. 3:1826-1838. PNNL-SA-37874.
- Poet T.S., J.J. Soelberg, K.K. Weitz, T.J. Mast, R.A. Miller, B.D. Thrall, and R.A. Corley. 2003. "Mode of Action and Pharmacokinetic Studies of 2-Butoxyethanol in the Mouse with an Emphasis on Forestomach Dosimetry." Toxicological Sciences 71, no. 2:176-189. PNWD-SA-6155.
- Bull R.J., G.A. Orner, L.B. Sasser, R.S. Cheng, L.C. Stillwell, A.J. Stauber, and M.K. Lingohr, et al. 2002. "The Contribution of Dichloroacetate and Trichloroacetate to Liver Tumor Induction in Mice by Trichloroethylene." Toxicology and Applied Pharmacology 182, no. 1:55-65. PNWD-SA-5533. doi:10.1006/taap.2002.9427
- Bull R.J., G.A. Orner, R.S. Cheng, L.C. Stillwell, A.J. Stauber, L.B. Sasser, and M.K. Lingohr, et al. 2002. "Contribution of Dichloroacetate and Trichloroacetate to Liver Tumor Induction in Mice by Trichloroethylene." Toxicology and Applied Pharmacology 182, no. 1:55-65. PNWD-SA-5784.
- Gorbunov N.V., J.E. Morris, J.S. Greenberger, and B.D. Thrall. 2002. "Establishment of a novel clonal murine bone marrow stromal cell line for assessment of p53 responses to genotoxic stress." Toxicology 179, no. 3:257-266. PNNL-SA-36497.
- Holtom G.R., S.D. Colson, and B.D. Thrall. 2002. "Locating Molecules Using Optical Microscopy: 3-D Imaging by Coherent Anti-Stokes Raman Scattering." In IEEE International Symposium on Biomedical Imaging : proceedings : July 7-10, 2002, Ritz-Carlton Hotel, Washington, D.C., USA, 781-784. Piscataway, New Jersey:IEEE. PNNL-SA-36008.
- Lingohr M.K., R.J. Bull, J. Kato-Weinstein, and B.D. Thrall. 2002. "Dichloroacetate Stimulates Glycogen Accumulation in Primary Hepatocytes through an Insulin-Independent Mechanism." Toxicological Sciences 68. PNWD-SA-5785.
- Pasa-Tolic L., R. Harkewicz, G.A. Anderson, N. Tolic, Y. Shen, R. Zhao, and B.D. Thrall, et al. 2002. "Increased Proteome Coverage for Quantitative Peptide Abundance Measurements Based upon High Performance Separations and DREAMS FTICR Mass Spectrometry." Journal of the American Society for Mass Spectrometry 13, no. 8:954-963. PNNL-SA-35815.
- Sowa M.B., G.A. Kimmel, J.H. Miller, J.C. Mcdonald, M.K. Murphy, D.J. Strom, and B.D. Thrall, et al. 2002. "Spatially Resolved Single-Cell Irradiator to Study Bystander Responses to Low-LET Radiation." Radiation Research 158, no. 3:375-376. PNNL-SA-40190.
- Wind R.A., P.D. Majors, K.R. Minard, E.J. Ackerman, D.S. Daly, G.R. Holtom, and B.D. Thrall, et al. 2002. "Combined Confocal and Magnetic Resonance Microscopy." Applied Magnetic Resonance 22, no. 2:145-158. PNNL-SA-35466.
- Conrads T.P., K. Alving, T.D. Veenstra, M.E. Belov, G.A. Anderson, D.J. Anderson, and M.S. Lipton, et al. 2001. "Quantitative Analysis of Bacterial and Mammalian Proteomes using a Combination of Cysteine Affinity Tags and 15N-Metabolic Labeling." Analytical Chemistry 73, no. 9:2132-2139. PNNL-SA-34135.
- Holtom G.R., B.D. Thrall, B. Chin, H.S. Wiley, and S.D. Colson. 2001. "Achieving molecular selectivity in imaging using multiphoton Raman spectroscopy techniques." Traffic 2, no. 11:781-788. PNNL-SA-35318.
- Kato-Weinstein J., A.J. Stauber, G.A. Orner, B.D. Thrall, and R.J. Bull. 2001. "Differential Effects of Dihalogenated and Trihalogenated Acetates in the Liver of B6C3F1 Mice." Journal of Applied Toxicology 21, no. 2:81-89. PNWD-SA-5194.
- Kato-Weinstein J., A.J. Stauber, G.A. Orner, B.D. Thrall, and R.J. Bull. 2001. "Differential Effects of Dihalogenated and Trihalogenated Acetates in the Liver of B6C3F1 Mice." Journal of Applied Toxicology 21, no. 2:81-89. PNWD-SA-5314.
- Kato-Weinstein J., G.A. Orner, B.D. Thrall, and R.J. Bull. 2001. "Differences in the detection of c-Jun and ubiquitin immunoreactive proteins by different c-Jun antibodies." Toxicology Methods 11, no. 3:189-207. PNWD-SA-5197.
- Lingohr M.K., B.D. Thrall, and R.J. Bull. 2001. "Effects of Dichloroacetate (DCA) on Serum Insulin Levels and Insulin-controlled Signaling Proteins in Livers of Male B6C3F1 Mice." Toxicological Sciences 59, no. 1:178-184. PNWD-SA-5319.
- Gorbunov N.V., K.L. Epperly, W.L. Bigbee, R. Draviam, J.E. Morris, J.S. Greenberger, and B.D. Thrall. 2000. "Activation of nuclear factor kappa B, nitric oxide synthase II, and Tp53 in response of bone marrow stromal cells to the oxidative stress induced by hydrogen peroxide." Free Radical Biology & Medicine 29, no. 1:S56. PNWD-SA-5327.
- Miller D.L., S. Bao, R.A. Gies, and B.D. Thrall. 1999. "Ultrasonic Enhancement of Gene Transfection in Murine Melanoma Tumors." Ultrasound in Medicine and Biology 25, no. 9:1425-1430. PNWD-SA-5317.
- Mounho B.J., and B.D. Thrall. 1999. "The Extracellular Signal-Regulated Kinase Pathway Contributes to Mitogenic and Anti-apoptotic Effects of Peroxisome Proliferators In Vitro." Toxicology and Applied Pharmacology 159, no. 2:125-133. PNNL-SA-31462.
- Xu N., L. Pasa-Tolic, R.D. Smith, S. Ni, and B.D. Thrall. 1999. "Electrospray Ionization-Mass Spectrometry Study of the Interaction of Cisplatin-Adducted Oligonucleotides with Human XPA Minimal Binding Domain Protein." Analytical Biochemistry 272, no. 1:26-33. PNNL-SA-30454.
- Buchko G.W., S. Ni, B.D. Thrall, and M.A. Kennedy. 1998. "Structural Features of the Minimal DNA Binding Domain (M98-F219) of Human Nucleotide Excision Repair Protein XPA." Nucleic Acids Research 26, no. 11:2779-2788. PNNL-SA-29588.
- Bull R.J., G.A. Orner, J. Kato-Weinstein, B.D. Thrall, and M.K. Smith. 1998. "Effects of Dichloroacetate on Glycogen Metabolism in B6C3F1 Mice." Toxicology 130. PNNL-SA-30295.
- Hess N.J., G.W. Buchko, S. Ni, B.D. Thrall, M.A. Kennedy, S.D. Conradson, and F.J. Espinosa, et al. 1998. "Human Nucleotide Excision Repair Protein XPA: Extended X-ray Absorption Fine-Structure Evidence for a Metal-Binding Domain." Protein Science 7, no. 9:1970-1975. PNNL-SA-29836. doi:10.1002/pro.5560070912
- Kato-Weinstein J., M.K. Lingohr, G.A. Orner, B.D. Thrall, and R.J. Bull. 1998. "Effects of Dichloroacetate on Glycogen Metabolism in B6C3F1 Mice." Toxicology 130, no. 2-3:141-154. PNNL-SA-30295.
- Kato-Weinstein J., M.K. Smith, B.D. Thrall, and R.J. Bull. 1998. "Effects of dichloroacetate on carbohydrate metabolism in B6C3F1 mice." Toxicology 130.
- Buchko G.W., S. Ni, B.D. Thrall, and M.A. Kennedy. 1997. "Human Nucleotide Excision Repair Protein XPA: Expression and NMR Backbone Assignments of the 14.7 kDa Minimal Damaged DNA Binding Domain (Met98-Phe219)." Journal of Biomolecular NMR 10, no. 3:313-314. PNNL-SA-29061. doi:10.1023/A:1018321319578