University of Illinois
71 RAL, Box 63-5
600 South Mathews Avenue
Urbana, IL 61801
Additional Campus Affiliations
Professor, Carl R. Woese Institute for Genomic Biology
Professor, Beckman Institute for Advanced Science and Technology
Department Affiliate, Molecular and Integrative Physiology
CAS Professor, Center for Advanced Study
Professor, Micro and Nanotechnology Lab
Professor, Carle Illinois College of Medicine
Affiliate, Neuroscience Program
Professor Sweedler received his B.S. degree in Chemistry from the University of California at Davis in 1983, and his Ph.D. from the University of Arizona in 1989. Thereafter, he was an NSF Postdoctoral Fellow at Stanford University before joining the faculty at Illinois in 1991. His research interests are in bioanalytical chemistry and focus on developing new methods for assaying the chemistry occurring in nanoliter-volume samples and applying these analytical methods to characterize the small molecule and peptide cell-cell signaling molecules from systems ranging from microbial ecologies to animal nervous systems. Professor Sweedler is Editor-in-Chief of the journal Analytical Chemistry.
analytical neurochemistry, more specifically, studies on cell to cell signaling pathways involved in learning, memory, and behavior, as well as conserved aspects of cell-cell signaling in systems ranging from microbial biofilms to animal nervous systems and endocrine systems
We develop a variety of analytical measurement methodologies, including microfluidic/nanofluidic sampling, capillary electrophoresis separations, and mass spectrometry characterization. These technologies combine to form metabolomics and peptidomics workflows, with much of our efforts directed toward scaling these methods to the nanoliter and smaller volume levels. We are currently developing a range of mass spectrometry imaging approaches that allow thousands of individual cells to be characterized for their lipid, metabolite, and peptide contents. Many of these measurement capabilities are unique and not currently available elsewhere.
We use these approaches to study cell-to-cell signaling in a broad range of systems, including the central nervous system to uncover novel neurochemical pathways. Because neurotransmitters and neuromodulators are so well conserved across the entire animal kingdom, we work with a wide variety of animal models, from mollusks to insects to vertebrates. We use new peptidomic and metabolomic approaches—many developed by us—to characterize these signaling molecules from individual cells to entire brain regions.
Why are we interested in these compounds? Because of the important roles they play in behavior, learning, and memory. Cell-to-cell communication in the brain relies upon a surprising array of molecules, from gaseous molecules (e.g., nitric oxide) to classical transmitters (e.g., glutamate), as well as unexpected molecules (e.g., d-serine), and a range of peptides. We have discovered literally hundreds of new prohormones and even more putative neuropeptides, and the bioactivity of several of these novel neuropeptides characterized. We use the same approaches to study cell-cell signaling in microbial systems, including studies on the microbe / gut / brain axis in mammals.
One research area is to understand how networks of neurons and associated supporting cells such as glia can work together to confer emergent properties that give rise to behavior and memory. Specific queries address what molecules are present in specific cells and networks, and how they change based on network activity, animal behavior, or even on exposure to drugs.
In addition to the research described above, a number of collaborative projects are undertaken through the UIUC Neuroproteomics and Neurometabolomics Center on Cell-Cell Signaling.
Honors & Awards
Donald F. Hunt Distinguished Contributions in Proteomics Award
Visionary Award, American Diabetes Association
Malcom E. Pruitt Award, Council for Chemical Research
Torbern Bergman Medal from the Swedish Chemical Society
ANACHEM Award, Federation of Analytical and Spectroscopy Societies
The Analytical Chemistry Award, The American Chemical Society
Ralph N. Adams Award, The Pittsburgh Conference
Fellow of the American Chemical Society
Theophilus Redwood Lecturer, Royal Society of Chemistry
Viktor Mutt Prize, International Regulatory Peptide Society
Castro, D. C., Xie, Y. R., Rubakhin, S. S., Romanova, E. V., & Sweedler, J. V. (2021). Image-guided MALDI mass spectrometry for high-throughput single-organelle characterization. Nature Methods, 18(10), 1233-1238. https://doi.org/10.1038/s41592-021-01277-2
Clark, K. D., Lee, C., Gillette, R., & Sweedler, J. V. (2021). Characterization of Neuronal RNA Modifications during Non-associative Learning in Aplysia Reveals Key Roles for tRNAs in Behavioral Sensitization. ACS Central Science, 7(7), 1183-1190. https://doi.org/10.1021/acscentsci.1c00351
Jia, J., Ellis, J. F., Cao, T., Fu, K., Morales-Soto, N., Shrout, J. D., Sweedler, J. V., & Bohn, P. W. (2021). Biopolymer Patterning-Directed Secretion in Mucoid and Nonmucoid Strains of Pseudomonas aeruginosa Revealed by Multimodal Chemical Imaging. ACS Infectious Diseases, 7(3), 598-607. https://doi.org/10.1021/acsinfecdis.0c00765
Neumann, E. K., Ellis, J. F., Triplett, A. E., Rubakhin, S. S., & Sweedler, J. V. (2019). Lipid Analysis of 30 000 Individual Rodent Cerebellar Cells Using High-Resolution Mass Spectrometry. Analytical Chemistry, 91(12), 7871-7878. https://doi.org/10.1021/acs.analchem.9b01689
Checco, J. W., Zhang, G., Yuan, W. D., Le, Z. W., Jing, J., & Sweedler, J. V. (2019). Aplysia allatotropin-related peptide and its newly identified D-amino acid-containing epimer both activate a receptor and a neuronal target. Journal of Biological Chemistry, 293(43), 16862-16873. https://doi.org/10.1074/jbc.RA118.004367
Morales-Soto, N., Dunham, S. J. B., Baig, N. F., Ellis, J. F., Madukoma, C. S., Bohn, P. W., Sweedler, J. V., & Shrout, J. D. (2018). Spatially dependent alkyl quinolone signaling responses to antibiotics in Pseudomonas aeruginosa swarms. Journal of Biological Chemistry, 293(24), 9544-9552. https://doi.org/10.1074/jbc.RA118.002605
Jansson, E. T., Comi, T. J., Rubakhin, S. S., & Sweedler, J. V. (2016). Single Cell Peptide Heterogeneity of Rat Islets of Langerhans. ACS chemical biology, 11(9), 2588-2595. https://doi.org/10.1021/acschembio.6b00602
Wang, T. A., Yu, Y. V., Govindaiah, G., Ye, X., Artinian, L., Coleman, T. P., Sweedler, J. V., Cox, C. L., & Gillette, M. U. (2012). Circadian rhythm of redox state regulates excitability in suprachiasmatic nucleus neurons. Science, 337(6096), 839-842. https://doi.org/10.1126/science.1222826
Castro, D. C., Chan-Andersen, P., Romanova, E. V., & Sweedler, J. V. (Accepted/In press). Probe-based mass spectrometry approaches for single-cell and single-organelle measurements. Mass Spectrometry Reviews. https://doi.org/10.1002/mas.21841
Castro, D. C., Smith, K. W., Norsworthy, M. D., Rubakhin, S. S., Weisbrod, C. R., Hendrickson, C. L., & Sweedler, J. V. (2023). Single-Cell and Subcellular Analysis Using Ultrahigh Resolution 21 T MALDI FTICR Mass Spectrometry. Analytical Chemistry, 95(17), 6980-6988. https://doi.org/10.1021/acs.analchem.3c00393
Choe, K., Jindra, M. A., Hubbard, S. C., Pfleger, B. F., & Sweedler, J. V. (2023). MALDI-MS screening of microbial colonies with isomer resolution to select fatty acid desaturase variants. Analytical Biochemistry, 672, Article 115169. https://doi.org/10.1016/j.ab.2023.115169
Eberwine, J., Kim, J., Anafi, R. C., Brem, S., Bucan, M., Fisher, S. A., Grady, M. S., Herr, A. E., Issadore, D., Jeong, H., Kim, H. B., Lee, D., Rubakhin, S., Sul, J. Y., Sweedler, J. V., Wolf, J. A., Zaret, K. S., & Zou, J. (2023). Subcellular omics: a new frontier pushing the limits of resolution, complexity and throughput. Nature Methods, 20(3), 331-335. https://doi.org/10.1038/s41592-023-01788-0
Hellinger, R., Sigurdsson, A., Wu, W., Romanova, E. V., Li, L., Sweedler, J. V., Süssmuth, R. D., & Gruber, C. W. (2023). Peptidomics. Nature Reviews Methods Primers, 3(1), Article 25. https://doi.org/10.1038/s43586-023-00205-2