Biomedical Scientist
Biomedical Scientist


Ernesto Nakayasu is a senior research scientist focused on understanding molecular mechanisms of diseases. Nakayasu has been applying systems biology and mass spectrometry-based omics measurements to study how pathogens and metabolic alterations cause human diseases; the goal is to identify diagnostic and therapeutic targets. He has been integrating multi-omics approaches to develop biomarkers of diseases and to study signaling and metabolic pathways that are altered or targeted in infectious and metabolic diseases.

Research Interest

  • Infectious disease signaling and virulence  During an infection, the host-immune system recognizes the pathogen, which triggers a response to kill the invading organism. Similarly, the pathogen needs to recognize the host and to produce factors that help evade the host responses in order to survive and replicate. Nakayasu’s research is focused on understanding which host factors contribute to the immune response, as well as pathogen molecules that are recognized by the host and virulence factors that block protective cellular responses. He has been using mass spectrometry to study protein post-translational modifications (e.g. phosphorylation, ubiquitination, acetylation and ADP-ribosylation) that regulate the immune response and how virulence factors interfere in such processes. He has also been using proteomics, lipidomics, and metabolomics to characterize virulence factors and their mechanisms of secretion and action.
  • Systems biology of metabolic diseases  Despite the apparent distance between infectious and metabolic diseases disciplines, they are interconnected since metabolism is a main player in host responses to pathogens. Likewise, type 1 diabetes, a chronic metabolic disease, is driven by an autoimmune response that kills the insulin producing β cell of the pancreas. Nakayasu has been using mass spectrometry assays to discover and validate biomarkers that can predict or diagnose the onset of type 1 diabetes. He has also been applying integrative multi-omics analyses to understand the molecular mechanisms in β-cell death. These studies led to the identification of protective factors, such as the growth/differentiation factor 15 (GDF15) and ADP-ribose glycohydrolase ARH3.
  • Development of drugs, mechanisms of action and resistance  Development of new drugs is a continuous need due to the number of diseases that are without proper treatments and those that have seen a rise of resistance in treatment. Nakayasu’s research has been identifying therapeutic targets based on the role of disease. For instance, he has demonstrated that GDF15 is a potential target for developing drugs for type 1 diabetes. He has also been using systems biology to characterize the pathogen metabolic pathways (e.g. fungal lipid metabolism) to identify new chemotherapeutic targets. Using a similar approach, Nakayasu has been studying multi-drug resistant organisms, such as Methicillin-resistant Staphylococcus aureus and Candida auris.

Disciplines and Skills

  • Host-Pathogen Interactions
  • Type 1 Diabetes
  • Proteomics
  • Lipidomics
  • Metabolomics
  • Data Integration


  • PhD in Biological Sciences, University of Texas at El Paso, 2008
  • BS in Biological Sciences, Institute of Biosciences, University of Sao Paulo, 2003

Affiliations and Professional Service

  • Editorial Board Member, Vaccines
  • Editorial Board Member, Biomed Research International

Awards and Recognitions

  • M.T. Thomas Award for Outstanding Postdoctoral Achievement, PNNL (2014)
  • Outstanding Graduate Student in Biological Science Award, University of Texas at El Paso (2008)



  • Alcazar O., L.F. Hernandez, E.S. Nakayasu, P.D. Piehowski, C.K. Ansong, M.H. Abdulreda, and P. Buchwald. 2020. "Longitudinal Proteomics Analysis in the Immediate Microenvironment of Islet Allografts During Progression of Rejection." Journal of Proteomics 223. PNNL-SA-152172. doi:10.1016/j.jprot.2020.103826
  • Burnet M.C., D. Zamith-Miranda, H.M. Heyman, K.K. Weitz, E.L. Bredeweg, J.D. Nosanchuk, and E.S. Nakayasu. 2020. "Remodeling of the Histoplasma capsulatum membrane induced by monoclonal antibodies." Vaccines 8, no. 2:269. PNNL-SA-152362. doi:10.3390/vaccines8020269
  • Cleare L.G., D. Zamith-Miranda, H.M. Heyman, S.P. Couvillion, L. Nimrichter, M.L. Rodrigues, and E.S. Nakayasu, et al. 2020. "Media Matters! Alterations in the loading and release of Histoplasma capsulatumextracellular vesicles in response to different nutritional milieus." Cellular Microbiology 22, no. 9: Article No. e13217. PNNL-SA-151908. doi:10.1111/cmi.13217
  • Colli M.L., M. Ramos-Rodriquez, E.S. Nakayasu, M.I. Alvelos, M. Lopes, J.L. Hill, and J. Turatsinze, et al. 2020. "An integrated multi-omics approach identifies the landscape of interferon-α-mediated responses of human pancreatic beta cells." Nature Communications 11, no. 1: Article No. 2584. PNNL-SA-144581. doi:10.1038/s41467-020-16327-0
  • Gan N., H. Guan, Y. Huang, T. Yu, J. Fu, E.S. Nakayasu, and K. Puvar, et al. 2020. "Legionella pneumophila regulates the activity of UBE2N by deamidase-mediated deubiquitination." The EMBO Journal 39, no. 4:Article No. e102806. PNNL-SA-141791. doi:10.15252/embj.2019102806


  • Coelho C., L. Brown, M. Maryam, R. Vij, D.F. Smith, M.C. Burnet, and J.E. Kyle, et al. 2019. "Listeria monocytogenes Virulence Factors, including listeriolysin O, are Secreted in Biologically Active Extracellular Vesicles." Journal of Biological Chemistry 294, no. 4:1202-1217. PNNL-SA-128462. doi:10.1074/jbc.RA118.006472
  • Gan N., E.S. Nakayasu, P.J. Hollenbeck, and Z. Luo. 2019. "Legionella pneumophila inhibits immune signalling via MavC-mediated transglutaminase-induced ubiquitination of UBE2N." Nature Microbiology 4, no. 1:134-143. PNNL-SA-129705. doi:10.1038/s41564-018-0282-8
  • Gan N., X. Zhen, Y. Liu, X. Xu, C. He, J. Qiu, and Y. Liu, et al. 2019. "Regulation of phosphoribosyl ubiquitination by a calmodulin-dependent glutamylase." Nature 572, no. 7769:387-391. PNNL-SA-142888. doi:10.1038/s41586-019-1439-1
  • Gibbons B.C., T.L. Fillmore, Y. Gao, R.J. Moore, T. Liu, E.S. Nakayasu, and T.O. Metz, et al. 2019. "Rapidly Assessing the Quality of Targeted Proteomics Experiments through Monitoring Stable-Isotope Labeled Standards." Journal of Proteome Research 18, no. 2:694-699. PNNL-SA-137457. doi:10.1021/acs.jproteome.8b00688
  • McDermott J.E., J.R. Cort, E.S. Nakayasu, J.N. Pruneda, C.C. Overall, and J.N. Adkins. 2019. "Prediction of Bacterial E3 Ubiquitin Ligase Effectors using Reduced Amino Acid Peptide Fingerprinting." PeerJ 7. PNNL-SA-138492. doi:10.7717/peerj.7055
  • Nakayasu E.S., W. Qian, C. Evans-Molina, R. Mirmira, D.L. Eizirik, and T.O. Metz. 2019. "The role of proteomics in assessing beta-cell dysfunction and death in type 1 diabetes." Expert Review of Proteomics 16, no. 7:569-582. PNNL-SA-142336. doi:10.1080/14789450.2019.1634548
  • Stanfill B.A., S.M. Reehl, L.M. Bramer, E.S. Nakayasu, S.S. Rich, T.O. Metz, and M. Rewers, et al. 2019. "Extending Classification Algorithms to Case-Control Studies." Biomedical Engineering and Computational Biology 10. PNNL-SA-135302. doi:10.1177/1179597219858954
  • Yin L., H. Ma, E.S. Nakayasu, S.H. Payne, D.R. Morris, and C.S. Harwood. 2019. "Bacterial Longevity Requires Protein Synthesis and a Stringent Response." mBio 10, no. 5:e02189-19. PNNL-SA-143448. doi:10.1128/mBio.02189-19
  • Zamith-Miranda D., H.M. Heyman, L.G. Cleare, S.P. Couvillion, G. Clair, E.L. Bredeweg, and A. Gacser, et al. 2019. "Multi-omics signature of Candida Auris, an emerging and multidrug-resistant pathogen." mSystems 4, no. 4:e00257-19. PNNL-SA-140174. doi:10.1128/mSystems.00257-19


  • Akberdin I., D. Collins, R. Hamilton, D.Y. Oshchepkov, A.K. Shukla, C.D. Nicora, and E.S. Nakayasu, et al. 2018. "Rare Earth Elements Alter Redox Balance in Methylomicrobium alcaliphilum 20ZR." Frontiers in Microbiology 27. PNNL-SA-139645. doi:10.3389/fmicb.2018.02735
  • Baltazar L.M., D. Zamith-Miranda, M.C. Burnet, H. Choi, L. Nimrichter, E.S. Nakayasu, and J.D. Nosanchuk. 2018. "Concentration-dependent protein loading of extracellular vesicles released by Histoplasma capsulatum after antibody treatment and its modulatory action upon macrophages." Scientific Reports 8, no. 1: Article No. 8065. PNNL-SA-124828. doi:10.1038/s41598-018-25665-5
  • Callister S.J., T.L. Fillmore, C.D. Nicora, J.B. Shaw, S.O. Purvine, D.J. Orton, and R.A. White, et al. 2018. "Addressing the challenge of soil metaproteome complexity by improving metaproteome depth of coverage Through two-dimensional liquid chromatography." Soil Biology and Biochemistry 125. PNNL-SA-131999. doi:10.1016/j.soilbio.2018.07.018
  • Nicora C.D., K.E. Burnum-Johnson, E.S. Nakayasu, C.P. Casey, R.A. White, T. Roy Chowdhury, and J.E. Kyle, et al. 2018. "The MPLEx Protocol for Multi-Omic Analyses of Soil Samples." Journal of Visualized Experiments e57343, no. 135. PNNL-SA-129344. doi:10.3791/57343
  • Stanfill B.A., E.S. Nakayasu, L.M. Bramer, A.M. Thompson, C.K. Ansong, T. Clauss, and M.A. Gritsenko, et al. 2018. "Quality Control Analysis in Real-time (QC-ART): A Tool for Real-time Quality Control Assessment of Mass Spectrometry-based Proteomics Data." Molecular and Cellular Proteomics 17, no. 9:1824-1836. PNNL-SA-129934. doi:10.1074/mcp.RA118.000648


  • Burnum-Johnson K.E., J.E. Kyle, A.J. Eisfeld, C.P. Casey, K.G. Stratton, J.F. Gonzalez, and F. Habyarimana, et al. 2017. "MPLEx: A method for simultaneous pathogen inactivation and extraction of samples for multi-omics profiling." Analyst 142, no. 3:442-448. PNNL-SA-116063. doi:10.1039/c6an02486f
  • Liu Y., W. Zhu, Y. Tan, E.S. Nakayasu, C.J. Staiger, and Z. Luo. 2017. "A Legionella Effector Disrupts Host Cytoskeletal Structure by Cleaving Actin." PLoS Pathogens 13, no. 1:e1006186. PNNL-SA-124050. doi:10.1371/journal.ppat.1006186
  • Muralimanoharan S., C. Li, E.S. Nakayasu, C.P. Casey, T.O. Metz, P.W. Nathanielsz, and A. Maloyan. 2017. "Sexual dimorphism in the fetal cardiac response to maternal nutrient restriction." Journal of Molecular and Cellular Cardiology 108. PNNL-SA-123734. doi:10.1016/j.yjmcc.2017.06.006
  • Nakayasu E.S., M.C. Burnet, H.E. Walukiewicz, C.S. Wilkins, A.K. Shukla, S.M. Brooks, and M.J. Plutz, et al. 2017. "Ancient regulatory role of lysine acetylation in central metabolism." mBio 8, no. 6:Article No. e01894-17. PNNL-SA-124565. doi:10.1128/mBio.01894-17
  • Qiu J., K. Yu, X. Fei, Y. Liu, E.S. Nakayasu, P.D. Piehowski, and J.B. Shaw, et al. 2017. "A unique deubiquitinase that deconjugates phosphoribosyl-linked protein ubiquitination." Cell Research 27, no. 7:865-881. PNNL-SA-123995. doi:10.1038/cr.2017.66
  • Shakya B., W.D. Penn, E.S. Nakayasu, and D.J. Lacount. 2017. "The Plasmodium falciparum exported protein PF3D7_0402000 binds to erythrocyte ankyrin and band 4.1." Molecular and Biochemical Parasitology 216. PNNL-SA-127217. doi:10.1016/j.molbiopara.2017.06.002
  • Wang L., X. Cai, S. Wu, R. Bomjan, E.S. Nakayasu, K. Handler, and J.C. Hinton, et al. 2017. "InvS Coordinates Expression of PrgH and FimZ and Is Required for Invasion of Epithelial Cells by Salmonella enterica serovar Typhimurium." Journal of Bacteriology 199, no. 13:00824-16. PNNL-SA-127078. doi:10.1128/JB.00824-16
  • Yang J., L. Yin, F.H. Lessner, E.S. Nakayasu, S.H. Payne, K. Fixen, and L.A. Gallagher, et al. 2017. "Genes essential for phototrophic growth by a purple alphaproteobacterium." Environmental Microbiology 19, no. 9:3567-3578. PNNL-SA-124648. doi:10.1111/1462-2920.13852


  • Baltazar L.M., E.S. Nakayasu, T. Sobreira, H. Choi, A. Casadevall, L. Nimrichter, and J.D. Nosanchuk. 2016. "Antibody Binding Alters the Characteristics and Contents of Extracellular Vesicles Released by Histoplasma Capsulatum." mSphere 1, no. 2:Article No. e00085-15. PNNL-SA-121346. doi:10.1128/mSphere.00085-15
  • Nakayasu E.S., C.D. Nicora, A.C. Sims, K.E. Burnum-Johnson, Y. Kim, J.E. Kyle, and M.M. Matzke, et al. 2016. "MPLEx: a Robust and Universal Protocol for Single-Sample Integrative Proteomic, Metabolomic, and Lipidomic Analyses." mSystems 1, no. 3:e00043-16. PNNL-SA-114737. doi:10.1128/mSystems.00043-16
  • Qiu J., M.J. Sheedlo, K. Yu, Y. Tan, E.S. Nakayasu, C. Das, and X. Liu, et al. 2016. "Ubiquitination independent of E1 and E2 enzymes by bacterial effectors." Nature 533, no. 7601:120-124. PNNL-SA-117267. doi:10.1038/nature17657
  • Sontag R.L., E.S. Nakayasu, R.N. Brown, G.S. Niemann, M.A. Sydor, O. Sanchez, and C. Ansong, et al. 2016. "Identification of novel host interactors of effectors secreted by Salmonella and Citrobacter: SrfH regulates host kinase ERK2 phosphorylation." mSystems 1, no. 4:e00032-15. PNNL-SA-114706. doi:10.1128/mSystems.00032-15


  • Elfenbein J.R., L.A. Knodler, E.S. Nakayasu, C. Ansong, H.M. Brewer, L. Bogomolnaya, and L.G. Adams, et al. 2015. "Multicopy single-stranded DNA directs intestinal colonization of enteric pathogens." PLoS Genetics 11, no. 9:e1005472. PNNL-SA-112635. doi:10.1371/journal.pgen.1005472
  • Li J., C.C. Overall, E.S. Nakayasu, A.S. Kidwai, M.B. Jones, R. Johnson, and N.T. Nguyen, et al. 2015. "Analysis of the Salmonella regulatory network suggests involvement of SsrB and H-NS in sE-regulated SPI-2 gene expression." Frontiers in Microbiology 6. PNNL-SA-101010. doi:10.3389/fmicb.2015.00027
  • Li J., E.S. Nakayasu, C.C. Overall, R. Johnson, A.S. Kidwai, J.E. McDermott, and C. Ansong, et al. 2015. "Global analysis of Salmonella alternative sigma factor E on protein translation." Journal of Proteome Research 14, no. 4:1716-1726. PNNL-SA-105707. doi:10.1021/pr5010423
  • Nakayasu E.S., M.A. Sydor, R.N. Brown, R.L. Sontag, T. Sobreira, G.W. Slysz, and D.R. Humphrys, et al. 2015. "Identification of Salmonella Typhimurium deubiquitinase SseL substrates by immunoaffinity enrichment and quantitative proteomic analysis." Journal of Proteome Research 14, no. 9:4029-4038. PNNL-SA-101042. doi:10.1021/acs.jproteome.5b00574


  • Malouli D., S.G. Hansen, E.S. Nakayasu, E.E. Marshall, C.M. Hughes, A.B. Ventura, and R.M. Gilbride, et al. 2014. "Cytomegalovirus pp65 limits dissemination but is dispensable for persistence." Journal of Clinical Investigation 124, no. 5:1928-1944. PNNL-SA-91084. doi:10.1172/JCI67420
  • Nakayasu E.S., S. Wu, M.A. Sydor, A.K. Shukla, K.K. Weitz, R.J. Moore, and K.K. Hixson, et al. 2014. "A Method to determine lysine acetylation stoichiometries." International Journal of Proteomics 2014. PNNL-SA-96571. doi:10.1155/2014/730725


  • Ansong C., S. Wu, D. Meng, X. Liu, H.M. Brewer, B. Kaiser, and E.S. Nakayasu, et al. 2013. "Top-down proteomics reveals a unique protein S-thiolation switch in Salmonella Typimurium in response to infection-like conditions." Proceedings of the National Academy of Sciences of the United States of America 110, no. 25:10153-10158. PNNL-SA-92306. doi:10.1073/pnas.1221210110
  • Conlon B.P., E.S. Nakayasu, L.E. Fleck, M.D. LaFleur, V.M. Isabella, K. Coleman, and S.N. Leonard, et al. 2013. "Activated ClpP kills persisters and eradicates a chronic biofilm infection." Nature 503, no. 7476:365-370. PNNL-SA-98792. doi:10.1038/nature12790
  • Nakayasu E.S., C. Ansong, J.N. Brown, F. Yang, D. Lopez-Ferrer, W. Qian, and R.D. Smith, et al. 2013. "Evaluation of selected binding domains for the analysis of ubiquitinated proteomes." Journal of the American Society for Mass Spectrometry 24, no. 8:1214-1223. PNNL-SA-83169. doi:10.1007/s13361-013-0619-8
  • Nakayasu E.S., R. Tempel, X.A. Cambronne, V.A. Petyuk, M.B. Jones, M.A. Gritsenko, and M.E. Monroe, et al. 2013. "Comparative phosphoproteomics reveals components of host cell invasion and post-transcriptional regulation during Francisella infection." Molecular and Cellular Proteomics 12, no. 11:3297-3309. PNNL-SA-93942. doi:10.1074/mcp.M113.029850
  • Nakayasu E.S., R.N. Brown, C. Ansong, M.A. Sydor, S. Imtiaz, C. Mihai, and R.L. Sontag, et al. 2013. "Multi-omic data integration links Deleted in Breast Cancer 1 (DBC1) Degradation to Chromatin Remodeling in Inflammatory Response." Molecular & Cellular Proteomics. MCP12, no. 8:2136-2147. PNNL-SA-88392. doi:10.1074/mcp.M112.026138
  • Su D., A.K. Shukla, B. Chen, J. Kim, E.S. Nakayasu, Y. Qu, and U.K. Aryal, et al. 2013. "Quantitative Site-specific Reactivity Profiling of S-Nitrosylation in Mouse Skeletal Muscle Using Cysteinyl Peptide Enrichment Coupled with Mass Spectrometry." Free Radical Biology & Medicine 57. PNNL-SA-89035. doi:10.1016/j.freeradbiomed.2012.12.010


  • Ansong C.K., B.L. Deatherage, D.R. Hyduke, B. Schmidt, J.E. McDermott, M.B. Jones, and S. Chauhan, et al. 2012. "Studying Salmonellae and Yersiniae Host-Pathogen Interactions Using Integrated ‘Omics and Modeling." In Systems Biology. Current Topics in Microbiology and Immunology, edited by M Katze. 21-41. PNNL-SA-135981.  doi:10.1007/82_2012_247
  • Bordbar A., M.L. Mo, E.S. Nakayasu, A.C. Rutledge, Y. Kim, T.O. Metz, and M.B. Jones, et al. 2012. "Model-driven multi-omic data analysis elucidates metabolic immunomodulators of macrophage activation." Molecular Systems Biology 8. PNNL-SA-87903. doi:10.1038/msb.2012.21
  • Malouli D., E.S. Nakayasu, K. Viswanathan, D.G. Camp, W.L. Chang, P.A. Barry, and R.D. Smith, et al. 2012. "Reevaluation of the Coding Potential and Proteomic Analysis of the BAC Derived Rhesus Cytomegalovirus Strain 68-1." Journal of Virology 86, no. 17:8959-8973. PNNL-SA-87442. doi:10.1128/JVI.01132-12


  • McDermott J.E., H. Yoon, E.S. Nakayasu, T.O. Metz, D.R. Hyduke, A.S. Kidwai, and B.O. Palsson, et al. 2011. "Technologies and Approaches to Elucidate and Model the Virulence Program of Salmonella." Frontiers in Microbiology 2. PNNL-SA-78291. doi:10.3389/fmicb.2011.00121