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James M. Fulcher
Chemist

James M. Fulcher is a chemist at the Environmental Molecular Sciences Laboratory at Pacific Northwest National Laboratory (PNNL) 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 Interests

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

Education

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

Awards and Recognition

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

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) 

Publications

2023 

Park, J., F. Yu, J. M. Fulcher, S. M. Williams, K. Engbrecht, R. J. Moore, G. C. Clair, V. Petyuk, A. I. Nesvizhskii, Y. Zhu. “Evaluating Linear Ion Trap for MS3-Based Multiplexed Single-Cell Proteomics.” Analytical Chemistry 95 (3): 1888–1898. https://doi.org/10.1021/acs.analchem.2c03739

Martin, E. A., J. M. Fulcher, M. Zhou, M. E. Monroe, V. A. Petyuk. “TopPICR: A Companion R Package for Top-Down Proteomics Data Analysis.” Journal of Proteome Research 22 (2): 399–409. https://doi.org/10.1021/acs.jproteome.2c00570

Liao, Y.-C., J. M. Fulcher, D. J. Degnan, S. M. Williams, L. M. Bramer, D. Veličković, K. J. Zemaitis, M. Veličković, R. L. Sontag, R. J. Moore, et al. “Spatially Resolved Top-Down Proteomics of Tissue Sections Based on a Microfluidic Nanodroplet Sample Preparation Platform.” Molecular & Cellular Proteomics 22 (2): 100491. https://doi.org/10.1016/j.mcpro.2022.100491

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