Chemist
Chemist

Biography

Dr. James M. Fulcher is a chemist in Pacific Northwest National Laboratory’s (PNNL’s) Environmental Molecular Sciences Division and the Environmental Molecular Sciences Laboratory with more than 10 years of experience in analytical and biological chemistry. He acquired his PhD in biochemistry from the University of Utah after developing new chemical tools for the total chemical synthesis of large proteins and peptides. Much of this work provided him extensive experience in organic, organometallic, and analytical chemical techniques. As a postdoctoral research associate and staff scientist at PNNL, he has developed novel top-down mass-spectrometric-based approaches and applied them to disease-relevant investigations, particularly Alzheimer’s disease and type I/II diabetes. These approaches have also required development of new bioinformatic tools (TopPICR). Furthermore, he has advanced new capabilities in single-cell analysis that enable multimodal transcriptomics and proteomics from the same single cell (nanoSPLITS). His current focus is on applying and furthering the capabilities of nanoPOTS single-cell proteomics and nanoSPLITS. 

Research Interest

  • High-performance liquid chromatography 
  • Fourier transform mass spectrometry 
  • MALDI mass spectrometry 
  • Single-cell proteomics and transcriptomics 
  • Top-down proteomics 
  • Solid-phase peptide synthesis 

Disciplines and Skills

  • High-performance liquid chromatography
  • Fourier transform mass spectrometry
  • Tandem mass spectrometry
  • MALDI mass spectrometry
  • Proteomics
  • Solid phase peptide synthesis
  • Organic chemistry

Education

  • PhD in biochemistry, University of Utah School of Medicine 
  • BS in biology, Nicholls State University 

Affiliations and Professional Service

  • American Society for Mass Spectrometry, Member (2018–Present) 
  • U.S. Human Proteome Organization, Member (2015–Present) 
  • American Chemical Society, Member (2014–Present) 

Awards and Recognitions

  • Marjorie Riches Gunn Award for Graduate Student Excellence, University of Utah School of Medicine 

Publications

2025

  • Zemaitis K., J.M. Fulcher, R. Kumar, D.J. Degnan, L.A. Lewis, Y. Liao, and M. Velickovic, et al. 2025. "Spatial top-down proteomics for the functional characterization of human kidney." Clinical Proteomics 22:Art. No. 9. PNNL-SA-193767. doi:10.1186/s12014-025-09531-x

2024

  • Fulcher J.M., L. Markillie, H.D. Mitchell, S.M. Williams, K.M. Engbrecht, D.J. Degnan, and L.M. Bramer, et al. 2024. "Parallel measurement of transcriptomes and proteomes from same single cells using nanodroplet splitting." Nature Communications 15, no. _:Art. No. 10614. PNNL-SA-205430. doi:10.1038/s41467-024-54099-z
  • Kumar R., K. Zemaitis, J.M. Fulcher, and L. Pasa-Tolic. 2024. "Advances in mass spectrometry-enabled multiomics analyses at single-cell resolution." Current Opinion in Biotechnology 87. PNNL-SA-194867. doi:10.1016/j.copbio.2024.103096
  • Kwon Y., J.M. Fulcher, L. Pasa-Tolic, and W. Qian. 2024. "Spatial Proteomics towards Cellular Resolution." Expert Review of Proteomics 21, no. 12:505 - 514. PNNL-SA-203070. doi:10.1080/14789450.2024.2445809

2023

  • Chen Y., A.J. Taylor, J.M. Fulcher, A.C. Swensen, X. Dai, M. Komba, and K.L. Wrightson, et al. 2023. "Deletion of carboxypeptidase E in beta cells disrupts proinsulin processing but does not lead to spontaneous development of diabetes in mice." Diabetes 72, no. 9:1277-1288. PNNL-SA-186901. doi:10.2337/db22-0945
  • Degnan D.J., K. Zemaitis, L.A. Lewis, L. McCue, L.M. Bramer, J.M. Fulcher, and D. Velickovic, et al. 2023. "IsoMatchMS: Open-Source Software for Automated Annotation and Visualization of High Resolution MALDI-MS Spectra." Journal of the American Society for Mass Spectrometry 34, no. 9:2061-2064. PNNL-SA-184623. doi:10.1021/jasms.3c00180
  • Fulcher J.M., A.C. Swensen, Y. Chen, B. Verchere, V.A. Petyuk, and W. Qian. 2023. "Top-Down Proteomics of Mouse Islets With Beta Cell CPE Deletion Reveals Molecular Details in Prohormone Processing." Endocrinology 164, no. 12:Art. No. bqad160. PNNL-SA-188096. doi:10.1210/endocr/bqad160
  • Fulcher J.M., L. Markillie, H.D. Mitchell, S.M. Williams, K.M. Engbrecht, R.J. Moore, and W.B. Chrisler, et al. 2023. Parallel measurement of transcriptomes and proteomes from same single cells using nanodroplet splitting. PNNL-34730. Richland, WA: Pacific Northwest National Laboratory. Parallel measurement of transcriptomes and proteomes from same single cells using nanodroplet splitting
  • Liao Y., J.M. Fulcher, D.J. Degnan, S.M. Williams, L.M. Bramer, D. Velickovic, and K. Zemaitis, et al. 2023. "Spatially resolved top-down proteomics of tissue sections based on a microfluidic nanodroplet sample preparation platform." Molecular & Cellular Proteomics 22, no. 2:Art. No. 100491. PNNL-SA-174522. doi:10.1016/j.mcpro.2022.100491
  • Martin E.A., J.M. Fulcher, M. Zhou, M.E. Monroe, and V.A. Petyuk. 2023. "TopPICR: a companion R package for top-down proteomics data analysis." Journal of Proteome Research 22, no. 2:399-409. PNNL-SA-177756. doi:10.1021/acs.jproteome.2c00570
  • Park J., F. Yu, J.M. Fulcher, S.M. Williams, K.M. Engbrecht, R.J. Moore, and G. Clair, et al. 2023. "Evaluating linear ion trap for MS3-based multiplexed single-cell proteomics." Analytical Chemistry 95, no. 3:1888-1898. PNNL-SA-176981. doi:10.1021/acs.analchem.2c03739

2022 

  • Zhou, M.*, J. M. Fulcher*, K. J. Zemaitis, D. J. Degnan, Y.-C. Liao, M. Veličković, D. Veličković, L. M. Bramer, W. R. Kew, G. Stacey, et al. “Discovery top-down proteomics in symbiotic soybean root nodules.” Frontiers in Analytical Science, 2. https://doi.org/10.3389/frans.2022.1012707. (* indicates co-first author) 
  • Chen, Y.-C., A. J.  Taylor, J. M. Fulcher, A. C. Swensen, X.-Q. Dai, M. Komba, K. L. C. Wrightson, K. Fok, A. E. Patterson, R. I. Klein-Geltink, et al. “Deletion of carboxypeptidase E in beta cells disrupts proinsulin processing and alters beta cell identity in mice.” bioRxiv. https://doi.org/10.1101/2022.10.20.512925. 
  • Fulcher, J. M., L. M. Markillie, H. D. Mitchell, S. M. Williams, K. M. Engbrecht, R. J. Moore, J. Cantlon-Bruce, J. W. Bagnoli, A. Seth, L. Paša-Tolić, Y. Zhu. “Parallel measurement of transcriptomes and proteomes from same single cells using nanodroplet splitting.” bioRxiv. https://doi.org/10.1101/2022.05.17.492137. 

2021 

  • Erickson, P. W.*, J. M. Fulcher*, P. Spaltenstein, M. S. Kay. “Traceless Click-Assisted Native Chemical Ligation Enabled by Protecting Dibenzocyclooctyne from Acid-Mediated Rearrangement with Copper(I).” Bioconjugate Chemistry 32 (10): 2233–2244. https://doi.org/10.1021/acs.bioconjchem.1c00403. (* indicates co-first author) 
  • Fulcher, J. M., A. Makaju, R. J. Moore, M. Zhou, D. A. Bennett, P. L. De Jager, W.-J. Qian, L. Paša-Tolić, V. A. Petyuk. “Enhancing Top-Down Proteomics of Brain Tissue with FAIMS.” Journal of Proteome Research, 20 (5): 2780–2795. https://doi.org/10.1021/acs.jproteome.1c00049. 
  • Giesler, R. J.*, J. M. Fulcher*, M. T. Jacobsen, M. S. Kay. “Controlling Segment Solubility in Large Protein Synthesis.” In Total Chemical Synthesis of Proteins, edited by A. Brik, P. Dawson, and L. Liu, 185–209. John Wiley & Sons, Ltd. https://doi.org/10.1002/9783527823567.ch7. (* indicates co-first author) 

2019 

  • Fulcher, J. M., M. E. Petersen, R. J. Giesler, Z. S. Cruz, D. M. Eckert, J. N. Francis, E. M. Kawamoto, M. T. Jacobsen, M. S. Kay. “Chemical synthesis of Shiga toxin subunit B using a next-generation traceless “helping hand” solubilizing tag.” Organic & Biomolecular Chemistry 17 (48): 10237–10244. https://doi.org/10.1039/C9OB02012H. 
  • Han, H., J. M. Fulcher, V. P. Dandey, J. H. Iwasa, W. I. Sundquist, M. S. Kay, P. S. Shen, C. P. Hill. “Structure of Vps4 with circular peptides and implications for translocation of two polypeptide chains by AAA+ ATPases.” eLife 8: e44071. https://doi.org/10.7554/eLife.44071. 

2017 

  • Sdano, M. A., J. M. Fulcher, S. Palani, M. B. Chandrasekharan, T. J. Parnell, F. G. Whitby, T. Formosa, C. P. Hill. “A novel SH2 recognition mechanism recruits Spt6 to the doubly phosphorylated RNA polymerase II linker at sites of transcription.” eLife 6: e28723. https://doi.org/10.7554/eLife.28723. 

2016 

  • Yost, C. C., H. Schwertz, M. J. Cody, J. A. Wallace, R. A. Campbell, A. Vieira-de-Abreu, C. V. Araujo, S. Schubert, E. S. Harris, J. W. Rowley, M. T. Rondina, J. M. Fulcher, C. L. Koening, A. S. Weyrich,  G. A. Zimmerman. “Neonatal NET-inhibitory factor and related peptides inhibit neutrophil extracellular trap formation.” The Journal of Clinical Investigation 126 (10): 3783–3798. https://doi.org/10.1172/JCI83873. 
  • Velinder, M., J. Singer, D. Bareyan, J. Meznarich, C. M. Tracy, J. M. Fulcher, D. McClellan, H. Lucente, S. Franklin, S. Sharma, M. E. Engel. “GFI1 functions in transcriptional control and cell fate determination require SNAG domain methylation to recruit LSD1.” Biochemical Journal 473 (19): 3355–3369. https://doi.org/10.1042/BCJ20160558. 

2014 

  • Fulcher, J. M., D. G. Wayment, P. M. White, C. L. Webber. “Pyraclostrobin Wash-off from Sugarcane Leaves and Aerobic Dissipation in Agricultural Soil.” Journal of Agricultural and Food Chemistry 62 (10): 2141–2146. https://doi.org/10.1021/jf405506p.