About

The Li Research Group is a multi-disciplinary cohort of highly talented graduate and post-graduate researchers. Heavily focusing on neuropeptidomic discovery, proteome profiling/quantitation, and novel instrumentation strategies, the LRG empowers each of its 25+ members towards optimal achievement.

Research topics

• Chemistry
• Biochemistry
• Biology
• Chromatography
• Medicine
• Pathology
• Neuroscience
• Computer Science
• Immunology
• Computational biology
• Internal medicine
• Virology
• Anatomy
• Endocrinology
• Nanotechnology
• Bioinformatics
• Intensive care medicine
• Veterinary medicine
• Organic chemistry
• Materials science
• Database

Selected publications

• Evaluation of Collagen Alterations in Early Precursor Lesions of High Grade Serous Ovarian Cancer by Second Harmonic Generation Microscopy and Mass Spectrometry

  Cancers · 2021 · 23 citations

  • Pathology
  • Chemistry
  • Medicine

  This work provides new insights into ECM remodeling in early ovarian cancer and suggests the combined use of SHG microscopy and mass spectrometry as a new diagnostic/prognostic approach.

  DOI

• In-depth Site-specific Analysis of N-glycoproteome in Human Cerebrospinal Fluid and Glycosylation Landscape Changes in Alzheimer's Disease

  Molecular & Cellular Proteomics · 2021 · 77 citations

  Senior authorCorresponding
  • Chemistry
  • Biochemistry
  • Computational biology

  As the body fluid that directly interchanges with the extracellular fluid of the central nervous system (CNS), cerebrospinal fluid (CSF) serves as a rich source for CNS-related disease biomarker discovery. Extensive proteome profiling has been conducted for CSF, but studies aimed at unraveling site-specific CSF N-glycoproteome are lacking. Initial efforts into site-specific N-glycoproteomics study in CSF yield limited coverage, hindering further experimental design of glycosylation-based disease biomarker discovery in CSF. In the present study, we have developed an N-glycoproteomic approach that combines enhanced N-glycopeptide sequential enrichment by hydrophilic interaction chromatography (HILIC) and boronic acid enrichment with electron transfer and higher-energy collision dissociation (EThcD) for large-scale intact N-glycopeptide analysis. The application of the developed approach to the analyses of human CSF samples enabled identifications of a total of 2893 intact N-glycopeptides from 511 N-glycosites and 285 N-glycoproteins. To our knowledge, this is the largest site-specific N-glycoproteome dataset reported for CSF to date. Such dataset provides molecular basis for a better understanding of the structure-function relationships of glycoproteins and their roles in CNS-related physiological and pathological processes. As accumulating evidence suggests that defects in glycosylation are involved in Alzheimer's disease (AD) pathogenesis, in the present study, a comparative in-depth N-glycoproteomic analysis was conducted for CSF samples from healthy control and AD patients, which yielded a comparable N-glycoproteome coverage but a distinct expression pattern for different categories of glycoforms, such as decreased fucosylation in AD CSF samples. Altered glycosylation patterns were detected for a number of N-glycoproteins including alpha-1-antichymotrypsin, ephrin-A3 and carnosinase CN1 etc., which serve as potentially interesting targets for further glycosylation-based AD study and may eventually lead to molecular elucidation of the role of glycosylation in AD progression.

  DOI

• Gold nanoparticles in virus detection: Recent advances and potential considerations for SARS‐CoV‐2 testing development

  Wiley Interdisciplinary Reviews Nanomedicine and Nanobiotechnology · 2021 · 76 citations

  • Virology
  • Intensive care medicine
  • Nanotechnology

  Viruses are infectious agents that pose significant threats to plants, animals, and humans. The current coronavirus disease 2019 pandemic, which is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has spread globally and resulted in over 2 million deaths and immeasurable financial losses. Rapid and sensitive virus diagnostics become crucially important in controlling the spread of a pandemic before effective treatment and vaccines are available. Gold nanoparticle (AuNP)-based testing holds great potential for this urgent unmet biomedical need. In this review, we describe the most recent advances in AuNP-based viral detection applications. In addition, we discuss considerations for the design of AuNP-based SARS-CoV-2 testings. Finally, we highlight and propose important parameters to consider for the future development of effective AuNP-based testings that would be critical for not only this COVID-19 pandemic, but also potential future outbreaks. This article is categorized under: Diagnostic Tools > Biosensing Diagnostic Tools > In Vitro Nanoparticle-Based Sensing.

  PublisherOA PDFDOI

• Quantification and molecular imaging of fatty acid isomers from complex biological samples by mass spectrometry

  Chemical Science · 2021 · 49 citations

  Senior authorCorresponding
  • Chemistry
  • Chromatography
  • Organic chemistry

  A structural lipidomics approach employs peracetic acid-induced epoxidation coupled with mass spectrometry for pinpointing CC bonds in unsaturated fatty acids, enabling both quantification and imaging of FA isomers from biological samples.

  PublisherOA PDFDOI

• Urinary Amine Metabolomics Characterization with Custom 12-Plex Isobaric DiLeu Labeling

  Journal of the American Society for Mass Spectrometry · 2020 · 12 citations

  Senior authorCorresponding
  • Chemistry
  • Internal medicine
  • Bioinformatics

  Lower urinary tract symptoms (LUTS) is common in aging males. Disease etiology is largely unknown but likely includes inflammation and age-related changes in steroid hormones. Diagnosis is currently based on subjective symptom scores, and mainstay treatments can be ineffective and bothersome. Biomarker discovery efforts could facilitate objective diagnostic criteria for personalized medicine and new potential druggable pathways. To identify urine metabolite markers specific to hormone-induced bladder outlet obstruction, we applied our custom synthesized multiplex isobaric tags to monitor the development of bladder outlet obstruction across time in an experimental mouse model of LUTS. Mouse urine samples were collected before treatment and after 2, 4, and 8 weeks of steroid hormone treatment and subsequently analyzed by nanoflow ultrahigh-performance liquid chromatography coupled to tandem mass spectrometry. Accurate and high-throughput quantification of amine-containing metabolites was achieved by 12-plex DiLeu isobaric labeling. Metandem, a novel online software tool for large-scale isobaric labeling-based metabolomics, was used for identification and relative quantification of labeled metabolites. A total of 59 amine-containing metabolites were identified and quantified, 9 of which were changed significantly by the hormone treatment. Metabolic pathway analyses showed that three metabolic pathways were potentially disrupted. Among them, the arginine and proline metabolism pathway was significantly dysregulated both in this model and in a prior analysis of LUTS patient samples. Proline and citrulline were significantly changed in both samples and serve as attractive candidate biomarkers. The 12-plex DiLeu isobaric labeling with Metandem data processing presents an accessible and efficient workflow for an amine-containing metabolome study in biological specimens.

  PublisherOA PDFDOI

• Neuropeptides in gut-brain axis and their influence on host immunity and stress

  Computational and Structural Biotechnology Journal · 2020 · 88 citations

  Senior authorCorresponding
  • Neuroscience
  • Biology
  • Immunology

  In recent decades, neuropeptides have been found to play a major role in communication along the gut-brain axis. Various neuropeptides are expressed in the central and peripheral nervous systems, where they facilitate the crosstalk between the nervous systems and other major body systems. In addition to being critical to communication from the brain in the nervous systems, neuropeptides actively regulate immune functions in the gut in both direct and indirect ways, allowing for communication between the immune and nervous systems. In this mini review, we discuss the role of several neuropeptides, including calcitonin gene-related peptide (CGRP), pituitary adenylate cyclase-activating polypeptide (PACAP), corticotropin-releasing hormone (CRH) and phoenixin (PNX), in the gut-brain axis and summarize their functions in immunity and stress. We choose these neuropeptides to highlight the diversity of peptide communication in the gut-brain axis.

  DOI

• On-Tissue Derivatization with Girard’s Reagent P Enhances N-Glycan Signals for Formalin-Fixed Paraffin-Embedded Tissue Sections in MALDI Mass Spectrometry Imaging

  Analytical Chemistry · 2020 · 68 citations

  Senior authorCorresponding
  • Chemistry
  • Biochemistry
  • Chromatography

  Glycosylation is a major protein post-translational modification whose dysregulation has been associated with many diseases. Herein, an on-tissue chemical derivatization strategy based on positively charged hydrazine reagent (Girard's reagent P) coupled with matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI-MSI) was developed for analysis of N-glycans from FFPE treated tissue sections. The performance of the proposed approach was evaluated by analysis of monosaccharides, oligosaccharides, N-glycans released from glycoproteins, as well as MS imaging of N-glycans from human cancer tissue sections. The results demonstrated that the signal-to-noise ratios for target saccharides were notably improved after chemical derivatization, in which signals were enhanced by 230-fold for glucose and over 28-fold for maltooctaose. Improved glycome coverage was obtained for N-glycans derived from glycoproteins and tissue samples after chemical derivatization. Furthermore, on-tissue derivatization was applied for MALDI-MSI of N-glycans from human laryngeal cancer and ovarian cancer tissues. Differentially expressed N-glycans among the tumor region, adjacent normal tissue region, and tumor proximal collagen stroma region were imaged, revealing that high-mannose type N-glycans were predominantly expressed in the tumor region. Overall, our results indicate that the on-tissue labeling strategy coupled with MALDI-MSI shows great potential to spatially characterize N-glycan expression within heterogeneous tissue samples with enhanced sensitivity. This study provides a promising approach to better understand the pathogenesis of cancer related aberrant glycosylation, which is beneficial to the design of improved clinical diagnosis and therapeutic strategies.

  PublisherOA PDFDOI

• Recent Advances in Analytical Approaches for Glycan and Glycopeptide Quantitation

  Molecular & Cellular Proteomics · 2020 · 86 citations

  Senior authorCorresponding
  • Computer Science
  • Computational biology
  • Chemistry

  Growing implications of glycosylation in physiological occurrences and human disease have prompted intensive focus on revealing glycomic perturbations through absolute and relative quantification. Empowered by seminal methodologies and increasing capacity for detection, identification, and characterization, the past decade has provided a significant increase in the number of suitable strategies for glycan and glycopeptide quantification. Mass-spectrometry-based strategies for glycomic quantitation have grown to include metabolic incorporation of stable isotopes, deposition of mass difference and mass defect isotopic labels, and isobaric chemical labeling, providing researchers with ample tools for accurate and robust quantitation. Beyond this, workflows have been designed to harness instrument capability for label-free quantification, and numerous software packages have been developed to facilitate reliable spectrum scoring. In this review, we present and highlight the most recent advances in chemical labeling and associated techniques for glycan and glycopeptide quantification.

  DOI

Recent grants

• Creating a region- specific biomolecular atlas of the brain of Alzheimer’s disease

  NIH · $3.0M · 2022–2027

• Exploiting ion mobility and high performance mass spectrometry for in-depth characterization of neuropeptides in hypoxia and pH stress

  NSF · $425k · 2017–2021

• NIH Grant RF1AG052324

  NIH · $2.4M · 2023

• NIH Grant R21AG055377

  NIH · $603k · 2019

• Combining Imaging Mass Spectrometry and Capillary Electrophoresis to Decipher Chemical Signaling in the Nervous System in Response to Environmental Stress

  NSF · $450k · 2010–2014

Frequent coauthors

• Miao Sun

  52 shared

• Andrew E. Christie

  51 shared

• Chenxi Jia

  Anhui Medical University

  42 shared

• M Ma

  Chengde Medical University

  40 shared

• Ruibing Chen

  Tianjin University

  39 shared

• Bingming Chen

  Merck & Co., Inc., Rahway, NJ, USA (United States)

  39 shared

• Jonathan V. Sweedler

  University of Illinois Urbana-Champaign

  37 shared

• Junfeng Huang

  Chinese Academy of Medical Sciences & Peking Union Medical College

  36 shared

Awards & honors

• Vilas Distinguished Achievement Professor of Pharmaceutical…
• Charles Melbourne Johnson Distinguished Chair in Pharmaceuti…

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