About

Jonathan V. Sweedler is the James R. Eiszner Endowed Chair and Professor in the Department of Bioengineering at the University of Illinois Urbana-Champaign. His primary research focuses on micro and molecular technologies, specifically chemical biosensors, high-throughput analysis, and instrumentation. He is involved in advancing bioengineering through the development of innovative tools and techniques for detecting and treating health issues, with a particular emphasis on neurochemistry and chemical biosensors. His work contributes to understanding complex biological systems and improving health-related diagnostics and therapies.

Research topics

• Chemistry
• Computer Science
• Chromatography
• Materials science
• Nanotechnology
• Biology
• Cell biology
• Neuroscience
• Computational biology
• Optoelectronics
• Artificial Intelligence
• Machine Learning
• Biophysics
• Medicine
• Biochemistry
• Bioinformatics
• Polymer chemistry
• Organic chemistry
• Optics
• Internal medicine
• Biological system
• Biomedical engineering
• Endocrinology
• Engineering

Selected publications

• Mass Spectrometry Imaging in ACS Journals

  ACS Measurement Science Au · 2026-04-28

  articleOpen access
  PublisherDOI

• Profiling Endogenous Opioid Peptide Release from Adrenal Chromaffin Cells

  ACS Chemical Neuroscience · 2026-05-06

  article

  Despite longstanding recognition that the adrenal medulla is a major source of both catecholamines and opioid peptides, direct measurements of opioid peptide release kinetics─and characterization of the full complexity of the peptidergic forms released─remain under studied. Here, this gap is addressed by introducing a workflow that integrates real-time electrochemical detection of catecholamine (CA) and enkephalin (ENK) release kinetics with tandem mass spectrometry to profile opioid peptide signaling from adrenal chromaffin cells. Fast-scan cyclic voltammetry was used to quantitatively monitor the exocytotic release of ENK peptides and CA from large dense-core vesicles in single chromaffin cells. Interestingly, ENK release events were evident on two separate time scales. The first phase of release was consistent with the codetected CA signal, suggesting release from the same population of vesicles. A slower signal was also present, suggestive of a strong association with the dense-core matrix and hindered mass transport. Liquid chromatography was coupled with mass spectrometry (LC-MS) to profile the activity-dependent opioid peptide release from these cells. The MS data show that proenkephalin-derived peptides dominate the adrenal peptidome, and that extended variants of M-ENK that contain the YGGFM motif plus additional amino acids, including YGGFM-RF, YGGFM-RGL, peptide E, BAM-18 and BAM-22, are actively released in response to both chemical and electrical stimulation. Overall, the results of this study inform on the temporal complexity and chemical diversity of peptide participants in opioid signaling while highlighting a versatile and powerful workflow for further exploration of these molecules in physiological systems.

  PublisherDOI

• Human plasma extracellular vesicles as an exercise mimetic to preserve skeletal muscle plasticity during disuse

  npj Microgravity · 2026-03-06

  articleOpen access

  The purpose of this study was to determine the extent to which extracellular vesicles (EVs) circulating in blood after exercise training act as an effective mimetic to maintain skeletal muscle mass during unloading and/or accelerate recovery after disuse. Ten healthy males (27.7 ± 7.1 y) were recruited for a 6-week progressive resistance and endurance training program. EVs were isolated from blood before (EVs) or immediately after training (ExerVs). EVs were intraperitoneally injected into male mice (4×; 3 × 108 particles/injection) during 14 days of hindlimb unloading (HU), then the muscles were collected immediately or 7 days after HU. ExerVs did not maintain muscle mass, fiber size (fCSA), or protein synthesis but significantly reduced collagen I during HU. ExerV administration rapidly restored Type I fCSA and capillary quantity concomitant with reduced collagen during the reloading period. Overall, this study demonstrates that ExerVs may represent a novel strategy to preserve skeletal muscle health during disuse.

  PublisherOA PDFDOI

• Local Chemical Gradients in a Mammalian Cortex Measured In Vivo With a Silicon Nanodialysis Mass Spectrometry Platform

  Angewandte Chemie · 2026-05-06

  articleOpen access

  ABSTRACT Chemical extrasynaptic signaling in the mammalian brain is involved in the control of behavior via modulation of neural activity, in wiring the brain by directing the axonal growth, in localization of pharmacological effects of drugs, and in regulating the neuroinflammation. Local gradients of various neurochemicals in the brain are difficult to study in vivo due to their complex spatiotemporal dynamics induced by intricate interactions between neurons and glial cells that are not well understood. Here, to directly measure in vivo gradients of multiple neurotransmitters and metabolites simultaneously, we utilize an open‐flow silicon nanodialysis sampling platform coupled with sensitive mass spectrometry. Results reveal strong millimeter‐scale spatial gradients in concentration of neurotransmitters, neuromodulators, and astroglial modulators in a mouse cortex. Formation and maintenance of such local chemical compartments indicate strong regulation of brain neurochemistry by glial‐neuron interactions that may heavily influence physiological and pathophysiological modulation of brain functions.

  PublisherDOI

• Local Chemical Gradients in a Mammalian Cortex Measured In Vivo With a Silicon Nanodialysis Mass Spectrometry Platform

  Angewandte Chemie International Edition · 2026-05-06

  articleOpen access

  Chemical extrasynaptic signaling in the mammalian brain is involved in the control of behavior via modulation of neural activity, in wiring the brain by directing the axonal growth, in localization of pharmacological effects of drugs, and in regulating the neuroinflammation. Local gradients of various neurochemicals in the brain are difficult to study in vivo due to their complex spatiotemporal dynamics induced by intricate interactions between neurons and glial cells that are not well understood. Here, to directly measure in vivo gradients of multiple neurotransmitters and metabolites simultaneously, we utilize an open-flow silicon nanodialysis sampling platform coupled with sensitive mass spectrometry. Results reveal strong millimeter-scale spatial gradients in concentration of neurotransmitters, neuromodulators, and astroglial modulators in a mouse cortex. Formation and maintenance of such local chemical compartments indicate strong regulation of brain neurochemistry by glial-neuron interactions that may heavily influence physiological and pathophysiological modulation of brain functions.

  PublisherDOI

• <i>Precision Chemistry</i> and <i>Analytical Chemistry</i> ─Two Synergistic Journals

  Precision Chemistry · 2026-02-25

  articleOpen access1st authorCorresponding
  PublisherDOI

• Quantification of <scp>D</scp> -Amino Acids in Type 1 Diabetes-Affected Human Serum

  Journal of the American Society for Mass Spectrometry · 2026-02-18

  articleSenior authorCorresponding

  Recent advances in understanding the roles of d-amino acids (d-AAs) in nervous and endocrine systems have highlighted their emerging significance in cell-to-cell signaling, particularly in diabetes, where d-AAs are localized in specific islet cell types. In type 1 diabetes (T1D), the autoimmune-mediated destruction of β-cells and the consequent reduction of insulin production impact the disease onset and progression. The presence of d-AAs in T1D serum allows us to understand if they are misregulated in T1D. Correlations between serum d-AAs, glycated hemoglobin (HbA1c), C-peptide levels, and disease duration in T1D patients are investigated. d/l-alanine, -proline, -aspartate, -serine, and -glutamate are quantified using chiral liquid chromatography-tandem mass spectrometry with a multiple-reaction-monitoring approach (LC-MRM-MS/MS). Additionally, d-cysteine levels are determined through a luciferase assay and confirmed via d-amino acid oxidase enzyme degradation. Positive correlations between d-glutamate and d-aspartate levels and C-peptide levels are observed. Obtained results demonstrate positive correlations between d-alanine, d-proline, and d-cysteine levels and disease duration, and a negative correlation with d-aspartate and d-glutamate. These findings suggest the involvement of a range of d-AAs and that serum d-AA levels may be indicators of T1D progression.

  PublisherDOI

• A brain-gut excitatory peptide/CCHamide homolog regulates satiation and motivational state transitions in the Aplysia feeding circuit

  Journal of Biological Chemistry · 2026-02-05

  articleOpen access

  Excitatory peptide (EP) and CCHamide (CCHa) are protostome neuropeptides originally identified in lophotrochozoans (including annelids and mollusks) and arthropods, respectively, and are homologous to the deuterostome endothelin (ET) and gastrin-releasing peptide (GRP)/neuromedin-B (NMB) systems. These peptides are brain-gut peptides: in vertebrates, GRP/NMB function as satiety peptides, whereas arthropod CCHa displays species-specific actions, either inhibiting or promoting feeding. However, the mechanisms by which these peptides modulate feeding circuits remain unknown. Here, we investigated the EP/CCHa signaling pathway in Aplysia, a mollusk with a well-defined feeding circuit. We identified a single precursor encoding Aplysia EP/CCHa (apEP/CCHa). Mass spectrometry demonstrated that an apEP/CCHa peptide is present in the central ganglia. In situ hybridization and immunohistochemistry revealed apEP/CCHa-positive neurons in the CNS, immunopositive cells in the gut, and immunopositive fibers in the gut-innervating esophageal nerve. To identify potential targets, we cloned two novel apEP/CCHa receptors. Phylogenetically, one receptor clusters with lophotrochozoan EP/CCHa receptors, whereas the other unexpectedly clusters with arthropod receptors, suggesting independent lineages for the two receptors. Single-cell RNA sequencing showed that both receptors are expressed in the key feeding central pattern generator (CPG) interneurons B20 and B34. Functionally, apEP/CCHa inhibited food intake in vivo and converted ingestive motor programs to egestive ones in vitro. At the circuit level, apEP/CCHa modulated excitability of B20 and B34, and two additional interneurons (B40, B64). In summary, we demonstrate that apEP/CCHa is a brain-gut peptide that functions as a satiation signal, and identify specific feeding CPG elements through which apEP/CCHa regulates motivational state transitions.

  PublisherDOI

• Choline supplementation partially reverses prefrontal neurochemical deficits induced by perinatal opioid exposure

  Scientific Reports · 2026-05-07

  articleOpen access

  Perinatal opioid exposure often compromises offspring executive function, affects offspring neuroimmune outcomes, and can impair neonatal striatal acetylcholine transmission. Therefore, we sought to examine the impact on prefrontal cortical (PFC) neurotransmission and determine whether adolescent dietary choline supplementation attenuates the effects of perinatal opioid exposure in male offspring. Using a mouse model, we found that perinatal morphine exposure reduced acetylcholine (33%) and choline (49%) in the PFC of male offspring in early adulthood, while leaving the striatum largely unaffected. Adolescent choline supplementation partially restored cholinergic deficits. While morphine exposure did not induce executive function deficits, choline supplementation improved attentional accuracy in the 5-choice serial reaction time task and reduced breakpoint in progressive ratio testing. Choline supplementation did not prevent increases in thigmotaxis after morphine exposure in male offspring. Perinatal morphine exposure increased expression of neuroinflammatory genes Apoe and Cd68 in the male basolateral amygdala, effects that were attenuated by choline supplementation. Together, these findings reveal defined neurochemical and molecular vulnerabilities to perinatal opioid exposure that may be mitigated by dietary choline supplementation. Choline supplementation was beneficial for executive function but did not specifically target morphine-induced behavioral changes. Importantly, this work is relevant for males and future work will assess female offspring.

  PublisherDOI

• Please Review, Review, and Review!

  Analytical Chemistry · 2026-03-03

  article1st authorCorresponding
  PublisherDOI

Recent grants

• Chemical-imaging guided characterization of cellular populations

  NSF · $405k · 2016–2019

• Molecular Profiling & Characterization

  NIH · $18.2M · 2004–2029

• NIH Grant R21DA014879

  NIH · $289k · 2004

• Characterizing Neuropeptides with Chiral Modifications

  NSF · $590k · 2004–2009

• NIH Grant R01EB002343

  NIH · $224k · 2005

Frequent coauthors

• Stanislav S. Rubakhin

  University of Illinois Urbana-Champaign

  200 shared

• Elena V. Romanova

  University of Illinois Urbana-Champaign

  98 shared

• Joan‐Emma Shea

  University of California, Santa Barbara

  89 shared

• Paul W. Bohn

  University of Notre Dame

  87 shared

• Bin Liu

  85 shared

• Marc A. Hillmyer

  University of Minnesota

  85 shared

• Joel D. Blum

  University of Michigan–Ann Arbor

  85 shared

• Kai Rossen

  85 shared

Labs

• Sweedler Research GroupPI

Education

• Ph.D., Bioengineering

  University of Illinois at Urbana-Champaign

  1991

• M.S., Bioengineering

  University of Illinois at Urbana-Champaign

  1987

• B.S., Bioengineering

  University of Illinois at Urbana-Champaign

  1985