**Now Accepting Applications for Pilot Research Project Grants--Read More**
About our Center
Our P30 Center at the University of Illinois' Beckman Institute has been funded by the National Institute on Drug Abuse since 2005, and was recently renewed for another five years until 2029. We provide proteomics, metabolomics, and bioinformatics technologies to biological collaborators at the University of Illinois Urbana-Champaign, and to members of the neuroscience community at other institutions. Our Center is built around the overarching theme of cell-cell signaling to advance state-of-the-art proteomics / metabolomics technologies focused on the study of addiction mechanisms in the central nervous system.
Why focus on cell-cell signaling? Intercellular signaling plays a crucial role in the organization and coordination of biological systems. A surprisingly large number of physicochemically and structurally distinct molecules are involved in communication among the cells of the brain, with more being discovered each year. These molecules range in size from the small nitric oxide molecule to large >100 kDa heavily post-translationally modified proteins. In addition, these are the endogenous molecules many of the drugs of abuse mimic in terms of receptor binding and other functions. Therefore, these molecules are particularly relevant in drug abuse research and present high-value targets for pharmacological intervention.
Center Structure
Scientific Research Cores
Services are provided to support our collaborators' projects via three synergistic scientific research cores: Sampling & Separation, Molecular Profiling & Characterization, and Bioinformatics, Data Analytics & Predictive Modeling. The services offered by the Neuroproteomics and Neurometabolomics Center on Cell-Cell Signaling are focused on several overarching goals:
Providing metabolomics / peptidomics / proteomics measurement capabilities and bioinformatics services to the Illinois, national and international neuroscience communities working on both fundamental neuroscience research and the study of drug addiction mechanisms.
Discovering the functional roles of metabolites, peptides and proteins in cell-cell signaling, memory, behavior and addiction.
Creating improved MS-based molecular characterization technologies to enable new investigations of cell-cell signaling.
Integrating proteomic and transcriptomic information in support of more accurate molecular identification and molecular network inference using systems biology approaches.
Pilot Research Project Core
In 2019 we added a Pilot Research Project Core to support promising young investigators new to addiction research, and also established researchers interested in exploring new directions in substance abuse research. Are you interested in applying for a pilot research project grant? Read more.
Administrative Core
The Administrative Core offers the support necessary to promote and maintain innovative scientific interactions while facilitating interactions among the three individual research cores and Center collaborators. Are you an established researcher who is interesting in collaborating with us? Read more.
**Center News**
Illinois News Bureau, April 2025: Jonathan Sweedler, Project Director, one of four Illinois investigators elected to the American Academy of Arts & Sciences.
Beckman Institute News: Jonathan Sweedler, Project Director, receives 2025 Vision and Spirit Award.
August 2024: National Institute on Drug Abuse renews funding for the Neuroproteomics and Neurometabolomics Center on Cell-Cell Signaling for five more years.
The Analytical Scientist Power List 2024: Jonathan Sweedler, Project Director, voted #4, and Neil Kelleher, Co-Investigator, are featured in the category, Human Health Heroes.
The Analytical Scientist Power List 2023: Jonathan Sweedler, Project Director, voted #3, and Neil Kelleher, Co-Investigator, are featured in the category, Leaders and Advocates.
NIH Instrument Grant Awarded: Illinois Congresswoman Nikki Budzinski announced on February 14, 2023, that the University of Illinois Urbana-Champaign will receive $1.25 million in federal grant funding from the NIH to purchase a high-end mass spectrometer, which will be used in part to support our NIDA Center's research related to addiction and drug misuse.
The Analytical Scientist Power List 2021:The 100 most influential people in the analytical sciences. Jonathan Sweedler, Project Director, voted #1; Neil Kelleher, Co-Investigator, voted in Top 20.
Research News: "Computational Method Provides Faster High-Resolution Mass Spectrometry Imaging".
The Analytical Scientist Power List 2019: The 100 most influential people in the analytical sciences. Jonathan Sweedler, Project Director, voted #1; Neil Kelleher, Co-Investigator, voted #12.
Beckman Institute News: "$6M Grant Renews Center That Seeks to Understand the Science of Drug Abuse".
Featured Collaborator
Jim Zaijie Wang is a Distinguished Professor of Pharmacology and Pharmaceutics at the University of Illinois Chicago. His research is focused on the neurobiological and molecular mechanisms underlying chronic pain and drug addiction, and the development of new pharmacological treatments for these conditions. More specifically, his objective is to understand the mechanisms leading to chronic pain, opioid tolerance and addiction, and opioid-induced hyperalgesia.
Our initial Pilot Research Project with Wang was centered around hemorphins, an unusual set of opioid peptides formed from the ‘degradation’ of hemoglobin. Interestingly, these are potent antipain peptides. To date there has been no study relating hemorphins (both their specific peptide forms and their levels) to sickle cell disease (SCD), a disease related to changes in the sequence of hemoglobin that can be accompanied by an unusual and debilitating pain phenotype. Our Center performed measurements in plasma and brain tissue to determine whether we could characterize plasma hemorphins from a mouse model of SCD. We implemented a quantitative mass spectrometric approach with the use of multiple reaction monitoring to determine whether hemorphin peptide levels in plasma, specifically LVVH7 and VVH7, are differentially regulated in their mouse model of SCD. In addition to measuring the changes based on sickle cell condition, these two peptides were correlated with each other.
Based on the success of the Pilot project, our effort with Wang is now a full study within our Sampling and Separation and Molecular Characterization Cores. We are quantifying hemorphins in microliter-volume plasma samples and central nervous system tissue of transgenic mice expressing a severe SCD phenotype and correlating this with its associated pain (nociceptive, inflammatory, and neuropathic). Our results indicate that LVVH7 and VVH7 hemorphin levels are reduced in the amygdala but increased in the plasma of our SCD mouse model, suggesting that hemorphin peptides might be involved in mediating pain in SCD.Featured Articles
Hemorphins, Atypical Endogenous Opiate Peptides, in Sickle Cell Disease and Their Association with Pain, Y. Tan, Y. Kashyap, E. De La Toba, S.W. Croslow, M. Gill, X. Guo, G. Ilktach, E. Davy, R. Molokie, Z.J. Wang, J.V. Sweedler, Pain 167, 2026, 326–337, DOI:10.1097/j.pain.0000000000003859. Sickle cell disease (SCD) is a genetic disorder caused by a mutation in the beta hemoglobin gene, resulting in red blood cell (RBC) distortion, hemolysis, and severe pain episodes. Despite advancements in understanding acute crisis pain that is caused by vaso-occlusion, the neurobiological mechanisms underlying chronic pain in SCD remain poorly studied. Hemorphins, atypical endogenous opioid peptides derived from the hemoglobin beta chain in RBCs have analgesic effects and may contribute to SCD-related pain mechanisms, as their formation occurs when hemoglobin in RBCs is exposed to proteases in plasma. In this study, we investigated the levels of hemorphins in both plasma and nervous system of humanized transgenic SCD mice using liquid chromatography mass spectrometry. Our results show a significant elevation of hemorphins in SCD mice compared with wild-type controls, with a strong correlation with individual pain levels. These findings suggest that altered hemorphin processing in SCD may contribute to chronic pain by modulating the opioid signaling pathways, offering insights into the neurobiology of pain in SCD.
*Related Commentary: New Kid on the Block: Hemorphins in Sickle Cell Disease, Donovan A. Argueta, Kalpna Gupta, DOI: 10.1097/j.pain.0000000000003860
Proteoform Profiling of Endogenous Single Cells from Rat Hippocampus at Scale, P. Su, M.A.R. Hollas, S. Rubakhin, F.A. Butun, J.B. Greer, B.P. Early, R.T. Fellers, M.A. Caldwell, J.V. Sweedler, J.O. Kafader, N.L. Kelleher, Nat. Biotechnol., 2025. DOI:10.1038/s41587-025-02669-x. We performed intact proteoform profiling of 10,809 endogenous single cells from the rat hippocampus using single-cell proteoform imaging mass spectrometry (scPiMS), which directly extracts whole proteins and demonstrates high throughput for MS-based single-cell proteomics compared with existing approaches.
- Featured in Bioengineer.org: Profiling Rat Hippocampus Proteoforms in Single Cells
Featured Reviews
Advances in Multimodal Mass Spectrometry for Single-Cell Analysis and Imaging Enhancement, S.W. Croslow, T.J. Trinklein, J.V. Sweedler, FEBS Lett. 598, 2024, 591–601.
Probe-Based Mass Spectrometry Approaches for Single-Cell and Single-Organelle Measurements, D.C. Castro, P. Chan-Andersen, E.V. Romanova, J.V. Sweedler, Mass Spectrom. Rev. 43, 2024, 888–912.