About

Zhijun Li is a professor in the Department of Biochemistry and Biophysics at the University of North Carolina at Chapel Hill. His research focuses on the molecular basis of RNA function, contributing to the understanding of RNA's role in biological processes. He is associated with the Zhang lab, where his work involves exploring the fundamental mechanisms underlying RNA activity and its implications in health and disease.

Research topics

• Neuroscience
• Biochemistry
• Biology
• Cell biology
• Virology
• Pharmacology
• Developmental psychology
• Psychology

Selected publications

• Genetic-algorithm-optimized honeycomb-reinforced metamaterial aerogel for broadband microwave absorption

  Composites Part B Engineering · 2026-05-06

  article1st author
  PublisherDOI

• Preclinical Theranostic Study of ⁶⁸ Ga/ ¹⁷⁷ Lu/ ²²⁵ Ac-Labeled Bicyclic Peptides Targeting Nectin-4 in Lung Cancer

  ACS Omega · 2026-05-22

  articleOpen accessCorresponding

  Nectin-4, a cell adhesion molecule frequently overexpressed in non-small cell lung cancer (NSCLC), has emerged as a promising target for theranostic applications due to its involvement in tumor progression and association with poor prognosis. This study aimed to develop radiolabeled agents based on bicyclic peptides for both imaging and targeted therapy for Nectin-4 positive tumors. We designed and synthesized 68Ga-labeled probes ([68Ga]Ga-3 and [68Ga]Ga-5) for PET imaging and 177Lu-labeled agents ([177Lu]Lu-6) for targeted radionuclide therapy. Radiochemical yields and purity were optimized, and the agents were evaluated for cellular uptake, internalization, and biodistribution in Nectin-4-expressing cell lines (H1975, ABC-1, HEK293nectin4) and xenograft models. Target specificity was confirmed through blocking studies with the Nectin-4 specific inhibitor peptide N188. The 68Ga-labeled probes exhibited high radiochemical yields (78–81%) and purity (>95%), with specific uptake observed in Nectin-4-positive cells (e.g., 69.20 ± 2.31%ID/106 cells for [68Ga]Ga-3 at 120 min) and tumors. Blocking studies resulted in significant reductions in uptake, with 39-fold and 22-fold decreases for [68Ga]Ga-3 and [68Ga]Ga-5, respectively, confirming Nectin-4 specificity. [177Lu]Lu-6 showed superior tumor retention (13% uptake) and internalization (3.5%) compared to [177Lu]Lu-FAP-2286/N188, with sustained tumor growth suppression in xenograft models. PET/SPECT imaging revealed high tumor-to-background ratios and favorable pharmacokinetics, highlighting the potential of these agents for clinical application.

  PublisherOA PDFDOI

• Longitudinal Analysis of Cannabinoid Type 1 Receptor in HIV-1 Tat Transgenic Mice Using PET Imaging and Western Blot Analysis

  Cannabis and Cannabinoid Research · 2026-05-21

  article

  Background: Cannabinoid type 1 receptor (CB 1 R) regulates glutamate release and plays a key role in neuroprotection and neuroinflammation. Since CB 1 R is implicated in HIV-associated neurocognitive disorders (HAND), it is important to determine how its expression changes with the neurotoxic human immunodeficiency virus type-1 (HIV-1) transactivator of transcription (Tat) protein. This study examined CB 1 R dynamics in an inducible HIV-1 Tat transgenic mouse model. Methods: Tat expression was induced in Tat(+) mice using doxycycline (DOX). Longitudinal positron emission tomography (PET) with the CB 1 R-selective radiotracer [ 11 C]-OMAR was performed at baseline, 2 weeks, and 3 months post-induction in Tat(–) and Tat(+) groups to track CB 1 R alterations across brain regions. Western blot analyses were conducted postmortem in the prefrontal cortex, striatum, hippocampus, cortex, cerebellum, and brainstem. Results: In a longitudinal PET imaging study, we observed a significant upregulation of CB 1 R expression in the cortex and cerebellum after 2 weeks of DOX treatment in both Tat(–) and Tat(+) mice; however, this increase was not maintained at the 3-month timepoint. Western blot analysis revealed region-specific changes in CB 1 R levels for both genotypes with upregulation observed at 2 weeks post DOX treatment. Notably, a significant interaction between genotype × DOX in the hippocampus, cerebellum, and brainstem exhibited significant CB 1 R alteration by Tat expression, suggesting region-dependent regulatory mechanisms. Conclusion: DOX treatment and Tat expression appear to affect CB 1 R levels in a region-specific manner, underscoring the complexity of HAND. The differences between PET imaging and Western blot results suggest that [ 11 C]-OMAR may lack the affinity and sensitivity to detect subtle CB 1 R changes at the 3-month timepoint. The low resolution of PET imaging may be another factor contributing to the detection limit. Lastly, these findings emphasize the importance of using multiple methodologies to capture nuanced molecular alterations in neuroinflammatory conditions.

  PublisherDOI

• ¹⁸ F‐Radiopharmaceutical Diversification Enabled by Deaminative Cross‐Electrophile Couplings

  Angewandte Chemie International Edition · 2025-12-04 · 2 citations

  articleOpen access

  Abstract The development of 18 F‐labelled radiotracers is of vital importance for (pre)clinical positron emission tomography (PET) imaging and to guide drug discovery campaigns. State‐of‐the‐art approaches often require labour‐intensive preparation of highly functionalised radiolabelling precursors. This bottleneck impedes analogue generation for optimal imaging and exploration of radiochemical space. To this end, we disclose a nickel‐mediated aryl (C) sp 2 ‐(C) sp 3 cross‐coupling with amine‐derived alkyl 2,4,6‐triphenylpyridinium salts as coupling partners amenable to radiosynthesis. The method was applied to primary and secondary 2,4,6‐triphenylpyridinium salts in radiochemical conversion (RCC) up to 86% and a high‐throughput experimentation (HTE) assay proved crucial for expedient ligand evaluation. A late‐stage diversification case study from a sole precursor achieved six 18 F‐labelled GSK‐3 kinase inhibitor analogues, one being prepared in up to gigabecquerel (GBq) quantities in a (semi)automated two‐step protocol applied across three commercial radiosynthesis platforms.

  PublisherOA PDFDOI

• Niclosamide nanoparticles as a novel adjuvant reverse colistin resistance via multiple mechanisms against multidrug-resistant <i>Salmonella</i> infections

  Microbiology Spectrum · 2025-10-20

  articleOpen access

  ABSTRACT The mobile colistin resistance ( mcr ) mechanism enables rapid horizontal transfer of resistance genes across food, animals, and humans, driving significant resistance in mcr -carrying bacteria. While numerous adjuvants can reverse colistin resistance, research on their dose–response relationships remains limited, and most suffer from poor solubility, low bioavailability, and safety issues, hindering clinical use. The dose–response analysis showed that niclosamide could achieve a high reversal efficiency within a relatively low concentration range. However, as the concentration of niclosamide increased, the ability to reverse colistin resistance remained unchanged, and the reversal efficiency gradually decreased. Mechanistic analyses reveal that its synergistic antibacterial effect with colistin involves disrupting bacterial membrane permeability, dissipating proton motive force, and inhibiting efflux pumps, leading to membrane damage, cytoplasmic leakage, ATP depletion, and accelerated reactive oxygen species-mediated oxidative damage, ultimately resulting in the death of bacterial cells. A niclosamide nanodelivery system (niclosamide-loaded mPEG-PLGA nanoparticles [NCL@mPEG-PLGA-NPs]) was developed to enhance bioavailability, significantly boosting colistin’s efficacy against Salmonella in vitro and in vivo . The in-depth study of the dose–response relationship of adjuvants in reversing colistin resistance and the establishment of the niclosamide nanodrug delivery system will lay a scientific foundation for the clinical application of colistin adjuvants and the development of suitable drug delivery systems. IMPORTANCE Colistin is used as a last resort for many infections caused by multidrug-resistant gram-negative bacteria, but colistin-resistant strains are on the rise. Studies have found that the combination of niclosamide and colistin exhibits significant synergistic antibacterial effects. Dose–response analysis shows that niclosamide has extremely high resistance reversal efficiency within a relatively low concentration range. The development of the new dosage form of NCL@mPEG-PLGA-NPs will lay a scientific foundation for the clinical application of colistin adjuvants and the development of drug delivery systems.

  PublisherDOI

• Honokiol ameliorates hepatic fibrosis by inducing lysosomal membrane permeabilization and impairing lipophagy in hepatic stellate cells

  Toxicology and Applied Pharmacology · 2025-11-07

  articleCorresponding
  PublisherDOI

• Bioequivalence assessment of high-capacity polymeric micelle nanoformulation of paclitaxel and Abraxane® in rodent and non-human primate models using a stable isotope tracer assay

  UNC Libraries · 2025-10-14

  articleOpen access
  PublisherDOI

• Study on the Microstructure and Properties of CoCrFeNiMo High-Entropy Alloy Coatings Prepared by Atmospheric Plasma Spraying

  Nanomaterials · 2025-11-08

  articleOpen access

  This study employed atmospheric plasma spraying (APS) technology to successfully fabricate CoCrFeNiMo high-entropy alloy (HEA) coatings under varying spraying currents and systematically investigated the effects of the spraying current on the microstructure, mechanical properties, and tribological behavior of the coatings. Results showed that the material composition remained consistent across different current levels, primarily consisting of face-centered cubic (FCC) solid solution phases, FeCr2O4 spinel phases, and Cr-rich FCC1 phases. The FCC matrix was dispersed with spherical Cr oxide particles smaller than 30 nm in diameter, which significantly enhanced the strength of the coatings. As spraying current increased, both porosity and microhardness exhibited a non-monotonic trend—initial optimization followed by deterioration. At 500 A spraying current, the coating achieved optimal performance, with the lowest porosity (0.42%) and highest microhardness (569.8 HV). Correspondingly, this condition also yielded the best wear resistance, with stable friction coefficients and wear rates reaching 0.49 and 6.91 × 10−5 mm3/N m, respectively. Abrasion surface analysis revealed that excessively low or high currents triggered distinct wear mechanisms leading to reduced wear resistance.

  PublisherOA PDFDOI

• Chaihu Longgu Muli Decoction attenuates chronic stress-induced endothelial dysfunction and potentiates chemotherapy in breast cancer by inhibiting cAMP/PKA/CREB1 mediated glycolysis

  Journal of Ethnopharmacology · 2025-09-30

  article1st authorCorresponding
  PublisherDOI

• Accelerated and Localized Synucleinopathy in a Hybrid Mouse Model: Implications for Positron Emission Tomography Studies

  Research Square · 2025-10-30

  preprintOpen access
  PublisherOA PDFDOI

Recent grants

• Novel Catalytic Methods for Efficient Radiolabeling of Un-activated Arene Compounds

  NIH · $2.2M · 2020–2025

• Development of IDO PET agents for immunotherapy

  NIH · $2.0M · 2018–2024

• NIH Grant R01EB014354

  NIH · $1.4M · 2018

• NIH Grant U54CA198999

  NIH · $23.7M · 2021

• NIH Grant S10OD023611

  NIH · $835k · 2020

Frequent coauthors

• Peter S. Conti

  University of Southern California

  359 shared

• Hui Wang

  First Affiliated Hospital of Anhui Medical University

  269 shared

• Zhanhong Wu

  University of North Carolina at Chapel Hill

  253 shared

• Mengzhe Wang

  207 shared

• Xiaohong Chen

  Hunan Cancer Hospital

  141 shared

• Ryan Park

  The University of Texas MD Anderson Cancer Center

  134 shared

• Joseph M. Fox

  National Institute of Standards and Technology

  93 shared

• Kantapat Chansaenpak

  National Nanotechnology Center

  89 shared

Labs

• Zhijun Li LabPI

Education

• Ph.D., Biochemistry and Biophysics

  University of North Carolina at Chapel Hill

  2023