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Lye Meng Markillie

Lye Meng Markillie is a biologist with the Cell Signaling and Communications team. She has more than 30 years of experience building multi-functional teams to address important science questions in molecular biology, immunology, and protein biochemistry. Her experience covers relationship development, experimental design and implementation, laboratory management, deployment of state-of-the-art laboratory instrumentation and techniques, and independent data analysis in different settings, including industry, university, and national laboratory.

She successfully deployed three different next-generation sequencing platforms (SOLiD™, Ion Torrent™, and illumina™) that support a wide range of applications, including whole transcriptome analysis, gene expression profiling, small RNA analysis, ChIP-Seq, and novel transcript identification, as well as genome and epigenome sequencing. She implements and oversees the workflow for sample preparation, library construction and data acquisition, as well as post instrument analysis of large data sets. Markillie supports multiple EMSL, the Environmental Molecular Sciences Laboratory, user projects and facilitates the progression, generation, and analysis of transcriptomic and genomic data.

She works with computational scientists and engineers to establish the transcriptomic and genomic analysis pipeline to handle large data sets, requiring use of PNNL Institutional computing resources to perform the analysis. In addition, she mentors undergraduate and graduate student interns in fulfillment of the PNNL's mission to educate future scientists and engineers of the nation.

Research Interests

  • Molecular Biology
  • Immunology
  • Protein Biochemistry


BS in Microbiology, Washington State University, 1990



Jiwei Zhang, Lye Meng Markillie, Hugh D Mitchell, Matthew J Gaffrey, Galya Orr, Jonathan S Schilling. “Distinctive carbon repression effects in the carbohydrate-selective wood decay fungus Rhodonia placenta” Fungal Genet Biol 2022 Feb 9;103673. doi: 10.1016/j.fgb.2022.103673.

Anderson C.E., J. Zhang, L. Markillie, H.D. Mitchell, W.B. Chrisler, M.J. Gaffrey, and G. Orr, et al. 2022. "Capturing an Early Gene Induction Event during Wood Decay by the Brown Rot Fungus Rhodonia placenta." Applied and Environmental Microbiology 88, no. 8:Art. No. e00188-22. PNNL-SA-172027. doi:10.1128/aem.00188-22

Smercina D.N., N.M. Zambare, K.S. Hofmockel, N.C. Sadler, E.L. Bredeweg, C.D. Nicora, and L. Markillie, et al. 2022. "Synthetic Soil Aggregates: Bioprinted Habitats for High Throughput Microbial Metaphenomics." Microorganisms 10, no. 5:Art. No. 944. PNNL-SA-171905. doi:10.3390/microorganisms10050944


Carrell AA, Veličković D, Lawrence TJ, Bowen BP, Louie KB, Carper DL, Chu RK, Mitchell HD, Orr G, Markillie LM, Jawdy SS, Grimwood J, Shaw AJ, Schmutz J, Northen TR, Anderton CR, Pelletier DA, Weston DJ. “Novel metabolic interactions and environmental conditions mediate the boreal peatmoss-cyanobacteria mutualism” ISME J. 2021 Nov 29. doi: 10.1038/s41396-021-01136-0.

Woo J, Williams SM, Markillie LM, Feng S, Tsai CF, Aguilera-Vazquez V, Sontag RL, Moore RJ, Hu D, Mehta HS, Cantlon-Bruce J, Liu T, Adkins JN, Smith RD, Clair GC, Pasa-Tolic L, Zhu Y. "High-throughput and high-efficiency sample preparation for single-cell proteomics using a nested nanowell chip” Nat Commun. 2021 Oct 29;12(1):6246. doi: 10.1038/s41467-021-26514-2.

Carlos del Cerro, Erika Erickson, Tao Dong, Allison R. Wong, Elizabeth K. Eder, Samuel O. Purvine, Hugh D. Mitchell, Karl K Weitz, Lye Meng Markillie, Meagan C. Burnet, David W. Hoyt, Rosalie K. Chu, Jan-Fang Cheng, Kelsey J. Ramirez, Rui Katahira, Wei Xiong, Michael E. Himmel, Venkataramanan Subramanian, Jeffrey G. Linger, and Davinia Salvachúa. “Intracelluar pathways for lignin catabolism in white-rot fungi” PNAS March 2, 2021 118 (9) e2017381118;

Tania Chroumpi, Mao Peng, Meng Markillie, Hugh Daniel Mitchell, Carrie D Nicora, Chelsea M Hutchinson, Vanessa Paurus, Nikola Tolic, Chaevien S Clendinen, Galya Orr, Scott E. Baker, Miia R. Mäkelä, Ronald P de Vries “Re-routing of sugar catabolism provides a better insight into fungal flexibility in using plant biomass-derived monomers as substrates” Front. Bioeng. Biotechnol., 08 March 2021 |

Boiteau R.M., L. Markillie, D.W. Hoyt, D. Hu, R.K. Chu, H.D. Mitchell, and L. Pasa-Tolic, et al. "Metabolic interactions between Brachypodium and Pseudomonas fluorescens under 1 controlled iron-limited conditions." 2021 mSystems 6(1):e00580-20. doi: 10.1128/mSystems.00580-20

Hu D., Y. Cui, L. Markillie, W.B. Chrisler, Q. Wang, R.S. Hatzenpichler, and G. Orr. "Counting mRNA copies in intact bacterial cells by fluctuation localization imaging-based fluorescence in situ hybridization (fliFISH)." Methods Mol Biol. 2021; 2246:237-247. doi: 10.1007/978-1-0716-1115-9_15 


Mensch A.C., H.D. Mitchell, L. Markillie, E. Laudadio, J. Orbeck, A. Dohnalkova, and M.P. Schwartz, et al. "Subtoxic dose of lithium cobalt oxide nanosheets impacts critical molecular pathways in trout gill epithelial cells." Environmental Science 2020: Nano 7, no. 11:3419-3430 

Daly P., M. Peng, H.D. Mitchell, Y. Kim, C.K. Ansong, H.M. Brewer, and P. De Gijsel, et al. 2020. "Colonies of the fungus Aspergillus niger are highly differentiated to adapt to local carbon source variation." Environmental Microbiology 22, no. 3:1154-1166. PNNL-SA-150305. doi:10.1111/1462-2920.14907

Hu D., Y. Cui, L. Markillie, W.B. Chrisler, Q. Wang, R.S. Hatzenpichler, and G. Orr. 2020. "Counting mRNA copies in intact bacterial cells by fluctuation localization imaging-based fluorescence in situ hybridization (fliFISH)." In Methods in Molecular Biology.


Dai, Y., H. A. Ogilvie, Y. Liu, M. Huang, L. M. Markillie, H. D. Mitchell, E. J. Borrego, M. V. Kolomiets, M. J. Gaffrey, G. Orr, E. W. Chehab, W. T. Mao, and J. Braam. 2019. “Rosette Core Fungal Resistance in Arabidopsis thaliana.” Planta 250 (6): 1941-1953.   

Martins, P. D., J. Frank, H. Mitchell, L. M. Markillie, and M. J. Wilkins. 2019. “Wetland Sediments Host Diverse Microbial Taxa Capable of Cycling Alcohols.” Applied and Environmental Microbiology 85 (12).

Zhang, J., H. D. Mitchell, L. M. Markillie, M. J. Gaffrey, G. Orr, and J. Schilling. 2019. “Reference Genes for Accurate Normalization of Gene Expression in Wood-Decomposing Fungi.” Fungal Genetics and Biology 123: 33-40.


Cui, Y., D. Hu, L. M. Markillie, W. B. Chrisler, M. J. Gaffrey, C. Ansong, L. Sussel, and G. Orr. 2018. “Fluctuation Localization Imaging-Based Fluorescence in Situ Hybridization (fliFISH) for Accurate Detection and Counting of RNA Copies in Single Cells.” Nucleic Acids Research 46 (2).

Howard-Varona C., K.R. Hargreaves, N.E. Solonenko, L. Markillie, R.A. White, H.M. Brewer, and C.K. Ansong, et al. 2018. "Multiple mechanisms drive phage infection efficiency in nearly-identical hosts." The ISME Journal 12, no. 2018:1605-1618. PNNL-SA-132683. doi:10.1038/s41396-018-0099-8

Khan N.E., Y. Maezato, R.S. McClure, C.J. Brislawn, J.M. Mobberley, N.G. Isern, and W.B. Chrisler, et al. 2018. "Phenotypic responses to interspecies competition and commensalism in a naturally-derived microbial co-culture." Scientific Reports 8. PNNL-SA-129337. doi:10.1038/s41598-017-18630-1


Howard-Varona, C., S. Roux, H. Dore, N. E. Solonenko, K. Holmfeldt, L. M. Markillie, G. Orr, and M. B. Sullivan. 2017. “Erratum: Regulation of Infection Efficiency in a Globally Abundant Marine Bacteriodetes Virus (the ISME Journal (2017) 11 1 (284-295)).” The ISME Journal 11 (8): 1942.

Howard-Varona C., S. Roux, H. Dore, N.E. Solonenko, K.M. Holmfeldt, L.M. Markillie, and G. Orr, et al. 2017. "Regulation of infection efficiency in a globally abundant marine Bacteriodetes virus." The ISME Journal 11, no. 1:284-295. PNNL-SA-115144. doi:10.1038/ismej.2016.81

Lindemann S.R., J.M. Mobberley, J.K. Cole, L. Markillie, R.C. Taylor, E.L. Huang, and W.B. Chrisler, et al. 2017. "Predicting Species-Resolved Macronutrient Acquisition during Succession in a Model Phototrophic Biofilm Using an Integrated 'Omics Approach." Frontiers in Microbiology 8. PNNL-SA-129376. doi:10.3389/fmicb.2017.01020

Orellana R., G. Chaput, L. Markillie, H.D. Mitchell, M.J. Gaffrey, G. Orr, and K.M. Deangelis. 2017. "Multi-time series RNA-seq analysis of Enterobacter lignolyticusSCF1 during growth in lignin-amended medium." PLoS One 12, no. 10:e0186440. PNNL-SA-131719. doi:10.1371/journal.pone.0186440

Staley C., A.P. Ferrieri, M.M. Tfaily, Y. Cui, R.K. Chu, P. Wang, and J.B. Shaw, et al. 2017. "Diurnal Cycling of Rhizosphere Bacterial Communities is Associated with Shifts in Carbon Metabolism." Microbiome 5. PNNL-SA-121718. doi:10.1186/s40168-017-0287-1


Bernstein H.C., R.S. McClure, E.A. Hill, L.M. Markillie, W.B. Chrisler, M.F. Romine, and J.E. McDermott, et al. 2016. "Unlocking the Constraints of Cyanobacterial Productivity: Acclimations Enabling Ultrafast Growth." mBio 7, no. 4:Article No. e00949-16. PNNL-SA-112394. doi:10.1128/mBio.00949-16

McClure R.S., C.C. Overall, J.E. McDermott, E.A. Hill, L.M. Markillie, L.A. McCue, and R.C. Taylor, et al. 2016. "Network Analysis of Transcriptomics Expands Regulatory Landscapes in Synechococcus sp. PCC 7002." Nucleic Acids Research 44, no. 18:8810-8825. PNNL-SA-113421. doi:10.1093/nar/gkw737

Mitchell H.D., L. Markillie, W.B. Chrisler, M.J. Gaffrey, D. Hu, C.J. Szymanski, and Y. Xie, et al. 2016. "Cells Respond to Distinct Nanoparticle Properties with Multiple Strategies as Revealed by Single-Cell RNA-Seq." ACS Nano 10, no. 11:10173-10185. PNNL-SA-121323. doi:10.1021/acsnano.6b05452

Shi T., M. Niepel, J.E. McDermott, Y. Gao, C.D. Nicora, W.B. Chrisler, and L.M. Markillie, et al. 2016. "Conservation of Protein Abundance Patterns Reveals the Regulatory Architecture of the of the EGFR-MAPK Pathway." Science Signaling 9, no. 436:rs6. PNNL-SA-115056. doi:10.1126/scisignal.aaf0891

Tilton S.C., L.M. Markillie, S. Hays, R.C. Taylor, and D.L. Stenoien. 2016. "Identification of differential gene expression patterns after acute exposure to high and low doses of low-LET ionizing radiation in a reconstituted human skin tissue." Radiation Research 186, no. 5:531-538. PNNL-SA-116819. doi:10.1667/RR14471.1


Bernstein H.C., M.A. Charania, R.S. McClure, N.C. Sadler, M.R. Melnicki, E.A. Hill, and L.M. Markillie, et al. 2015. "Multi-omic Dynamics Associate Oxygenic Photosynthesis with Nitrogenase-mediated H2 production in Cyanothece sp. ATCC 51142." Scientific Reports 5. PNNL-SA-111925. doi:10.1038/srep16004

Castelle C., K.C. Wrighton, B.C. Thomas, L.A. Hug, C.T. Brown, M.J. Wilkins, and K.R. Frischkorn, et al. 2015. "Genomic expansion of Domain Archaea highlights roles for organisms from new phyla in anaerobic carbon cycling." Current Biology 25, no. 6:690-701. PNNL-SA-104949. doi:10.1016/j.cub.2015.01.014


Beliaev A.S., M.F. Romine, M. Serres, H.C. Bernstein, B.E. Linggi, L.M. Markillie, and N.G. Isern, et al. 2014. "Inference of Interactions in Cyanobacterial-Heterotrophic Co-Cultures via Transcriptome Sequencing." The ISME Journal 8, no. 11:2243-2255. PNNL-SA-98626. doi:10.1038/ismej.2014.69

Croken M., Y. Ma, L.M. Markillie, R.C. Taylor, G. Orr, L.M. Weiss, and K. Kim. 2014. "Distinct Strains of Toxoplasma gondii Feature Divergent Transcriptomes Regardless of Developmental Stage." PLoS One 9, no. 11:Article No. e111297. PNNL-SA-104591. doi:10.1371/journal.pone.0111297

Eraso J.M., L.M. Markillie, H.D. Mitchell, R.C. Taylor, G. Orr, and W. Margolin. 2014. "The highly conserved MraZ protein is a transcriptional regulator in Escherichia coli." Journal of Bacteriology 196, no. 11:2053-2066. PNNL-SA-98128. doi:10.1128/JB.01370-13

Welkie D.G., X. Zhang, L.M. Markillie, R.C. Taylor, G. Orr, J.M. Jacobs, and K. Bhide, et al. 2014. "Transcriptomic and proteomic dynamics in the metabolism of a diazotrophic cyanobacterium, Cyanothece sp. PCC 7822 during a diurnal light-dark cycle." BMC Genomics 15. PNNL-SA-104956.

Wilkins M.J., D.W. Hoyt, M.J. Marshall, P.A. Alderson, A.E. Plymale, L.M. Markillie, and A.E. Tucker, et al. 2014. "CO2 exposure at pressure impacts metabolism and stress responses in the model sulfate-reducing bacterium Desulfovibrio vulgaris strain Hildenborough." Frontiers in Microbiology 5. PNNL-SA-103791. doi:10.3389/fmicb.2014.00507


DeAngelis K.M., D. Sharma, R. Varney, B.A. Simmons, N.G. Isern, L.M. Markillie, and C.D. Nicora, et al. 2013. "Evidence supporting dissimilatory and assimilatory lignin degradation in Enterobacter lignolyticus SCF1." Frontiers in Microbiology 4. PNNL-SA-96504.

Hess B.M., J. Xue, L.M. Markillie, R.C. Taylor, H.S. Wiley, B.K. Ahring, and B.E. Linggi. 2013. "Coregulation of terpenoid pathway genes and prediction of isoprene production in Bacillus subtilis using transcriptomics." PLoS One 8, no. 6:e66104. PNNL-SA-93488. doi:10.1371/journal.pone.0066104

Piao H., L.M. Markillie, D.E. Culley, R.I. Mackie, and M. Hess. 2013. "Improved Method for Isolation of Microbial RNA from Biofuel Feedstock for Metatranscriptomics." Advances in Microbiology 3, no. 1:101-107. PNNL-SA-90377. doi:10.4236/aim.2013.31016

Suvorova E.S., M. Croken, S. Kratzer, L. Ting, M. Conde de Felipe, B. Balu, and L.M. Markillie, et al. 2013. "Discovery of a Splicing Regulator Required for Cell Cycle Progression." PLoS Genetics 9, no. 2:Article No. e1003305. PNNL-SA-94022. doi:10.1371/journal.pgen.1003305

Taylor R.C., B.M. Webb-Robertson, L.M. Markillie, M.H. Serres, B.E. Linggi, J.T. Aldrich, and E.A. Hill, et al. 2013. "Changes in Translational Efficiency is a Dominant Regulatory Mechanism in the Environmental Response of Bacteria." Integrative Biology 5, no. 11:1393-1406. PNNL-SA-95628. doi:10.1039/C3IB40120K

Tomita T., D.J. Bzik, Y. Ma, B.A. Fox, L.M. Markillie, R.C. Taylor, and K. Kim, et al. 2013. "The Toxoplasma gondii cyst wall protein CST1 is critical for cyst wall integrity and promotes bradyzoite persistence." PLoS Pathogens 9, no. 12:e1003823. PNNL-SA-95899. doi:10.1371/journal.ppat.1003823

Walker R.W., L.M. Markillie, A.H. Colotelo, D.R. Geist, M.E. Gay, C.M. Woodley, and M.B. Eppard, et al. 2013. "Ultraviolet radiation as disinfection for fish surgical tools." Animal Biotelemetry 1. PNNL-SA-86919. doi:10.1186/2050-3385-1-4

Walker R.W., L.M. Markillie, A.H. Colotelo, M.E. Gay, C.M. Woodley, and R.S. Brown. 2013. The Efficacy of Ultraviolet Radiation for Sterilizing Tools Used for Surgically Implanting Transmitters into Fish. PNNL-21126. Richland, WA: Pacific Northwest National Laboratory. The Efficacy of Ultraviolet Radiation for Sterilizing Tools Used for Surgically Implanting Transmitters into Fish


Yang F., K.M. Waters, B.M. Webb-Robertson, M.B. Sowa, C.H. Freiin von Neubeck, J.T. Aldrich, and L.M. Markillie, et al. 2012. "Quantitative Phosphoproteomics Identifies Filaggrin and other Targets of Ionizing Radiation in a Human Skin Model." Experimental Dermatology 21, no. 5:352-357. PNNL-SA-79030. doi:10.1111/j.1600-0625.2012.01470.x


Labaj P.P., G.G. Leparc, B.E. Linggi, L.M. Markillie, H.S. Wiley, and D.P. Kreil. 2011. "Characterization and Improvement of RNA-Seq Precision in Quantitative Transcript Expression Profiling." Bioinformatics 27, no. 13:I383-I391. PNNL-SA-77408. doi:10.1093/bioinformatics/btr247

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

Zangar R.C., N. Bollinger, T.J. Weber, R. Tan, L.M. Markillie, and N.J. Karin. 2011. "Reactive Oxygen Species Alter Autocrine and Paracrine Signaling." Free Radical Biology & Medicine 51, no. 11:2041-2047. PNNL-SA-84606. doi:10.1016/j.freeradbiomed.2011.09.001


Chen B., L.M. Markillie, Y. Xiong, M.U. Mayer, and T.C. Squier. 2007. "Increased Catalytic Efficiency Following Gene Fusion of Bifunctional Methionine Sulfoxide Reductase Enzymes from Shewanella oneidensis." Biochemistry 46, no. 49:14153-14161. PNNL-SA-55899. doi:10.1021/bi701151t


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

Xiong Y., B. Chen, H.S. Smallwood, R.J. Urbauer, L.M. Markillie, N.A. Galeva, and T.D. Williams, et al. 2006. "High-Affinity and Cooperative Binding of Oxidized Calmodulin by Methionine Sulfoxide Reductase." Biochemistry 45, no. 49:14642-14654. PNWD-SA-7459. doi:10.1021/bi0612465


Chen B., M.U. Mayer, L.M. Markillie, D.L. Stenoien, and T.C. Squier. 2005. "Dynamic Motion of Helix A in the Amino-terminal Domain of Calmodulin is Stabilized Upon Calcium Activation." Biochemistry 44, no. 3:905-914. PNWD-SA-6572.

Galeva N.A., S. Esch, T.D. Williams, L.M. Markillie, and T.C. Squier. 2005. "Rapid Method for Quantifying the Extent of Methionine Oxidation in Intact Calmodulin." Journal of the American Society for Mass Spectrometry 16, no. 9:1470-80. PNWD-SA-7078.

Markillie L.M., C.T. Lin, J.N. Adkins, D.L. Auberry, E.A. Hill, B.S. Hooker, and P.A. Moore, et al. 2005. "Simple Protein Complex Purification and Identification Method Suitable for High- throughput Mapping of Protein Interaction Networks." Journal of Proteome Research 4, no. 2:268-274. PNNL-SA-42494. doi:10.1021/pr049847a

Shi L., C.T. Lin, L.M. Markillie, T.C. Squier, and B.S. Hooker. 2005. "Over-expression of Multi-heme C-type Cytochromes." BioTechniques 38, no. 2:297-299. PNNL-SA-41097.

Weber T.J., R.W. Siegel, L. Markillie, W.B. Chrisler, X.C. Lei, and N.H. Colburn. 2005. "A paracrine signal mediates the cell transformation response to low dose gamma radiation in JB6 cells." Molecular Carcinogenesis 43, no. 1:31-37. PNNL-SA-41438.


Jasionowski M., K.J. Krzyminski, W.B. Chrisler, L.M. Markillie, J.E. Morris, and A. Gutowska. 2004. "Thermally-reversible gels for 3D cell culture of chondrocytes." Journal of Materials Science. Materials in Medicine 15, no. 5:575-582. PNNL-SA-43425.


Weber T.J., and L.M. Markillie. 2003. "Regulation of Activator Protein-1 by 8-iso-Prostaglandin E2 in a Thromboxane A2 Receptor-Dependent and -Independent Manner." Molecular Pharmacology 63, no. 5:1075-81. PNNL-SA-42101.


Lipton M.S., L. Pasa-Tolic, G.A. Anderson, D.J. Anderson, D.L. Auberry, J.R. Battista, and M.J. Daly, et al. 2002. "Global Analysis of Deinococcus Radiodurans Proteome by Csing Accurate Mass Tags." Proceedings of the National Academy of Sciences of the United States of America 99, no. 17:11049-11054. PNNL-SA-35211.

Weber T.J., L.M. Markillie, W.B. Chrisler, G.A. Vielhauer, and J.W. Regan. 2002. "Modulation of JB6 Mouse Epidermal Cell Transformation Response by the Prostaglandin F2 alpha Receptor." Molecular Carcinogenesis 35, no. 4:163-172. PNNL-SA-38182.


Markillie L.M., S.M. Varnum, P.B. Hradecky, and K. Wong. 1999. "Targeted mutagenesis by duplication insertion in the radioresistant bacterium Deinococcus radiodurans: radiation sensitivities of catalase (katA) and superoxide dismutase (sodA) mutants." Journal of Bacteriology 181, no. 2:666-669. PNNL-SA-30309.


Wong K.K., L.M. Markillie, and J.D. Saffer. 1997. "A novel method for producing partial restriction digestion of DNA fragments by PCR with 5-methyl-CTP." Nucleic Acids Research 25, no. 20:4169