About

Dr. Fang Li is a professor recognized for his significant contributions to the field of structural biology of disease. For five consecutive years, from 2021 to 2025, Dr. Li has been named a Highly Cited Researcher by Web of Science (Clarivate), an honor that places him among the top 0.1% of researchers worldwide across all disciplines. In 2025, Dr. Li, along with members of his laboratory, Dr. Jian Shang and Dr. Yushun Wan, were included in this prestigious list, highlighting the impactful and widely recognized nature of their research. This consistent recognition underscores Dr. Li's leadership and influence in his research area at the University of Minnesota.

Research topics

• Biology
• Medicine
• Virology
• Biochemistry
• Genetics
• Chemistry
• Cell biology
• Immunology
• Biophysics
• Computational biology
• Pharmacology

Selected publications

• Molecularly imprinted polymer-electrochemiluminescence sensor based on lanthanum-doped graphite carbon nitride for the detection of bisphenol A

  SSRN Electronic Journal · 2025-01-01

  preprintOpen access
  PublisherDOI

• Cryo-EM structure of Sudan ebolavirus glycoprotein complexed with its human endosomal receptor NPC1

  Communications Biology · 2025-02-02 · 5 citations

  articleOpen accessSenior author

  Sudan ebolavirus (SUDV), like Ebola ebolavirus (EBOV), poses a significant threat to global health and security due to its high lethality. However, unlike EBOV, there are no approved vaccines or treatments for SUDV, and its structural interaction with the endosomal receptor NPC1 remains unclear. This study compares the glycoproteins of SUDV and EBOV (in their proteolytically primed forms) and their binding to human NPC1 (hNPC1). The findings reveal that the SUDV glycoprotein binds significantly more strongly to hNPC1 than the EBOV glycoprotein. Using cryo-EM, we determined the structure of the SUDV glycoprotein/hNPC1 complex, identifying four key residues in the SUDV glycoprotein that differ from those in the EBOV glycoprotein and influence hNPC1 binding: Ile79, Ala141, and Pro148 enhance binding, while Gln142 reduces it. Collectively, these residue differences account for SUDV's stronger binding affinity for hNPC1. This study provides critical insights into receptor recognition across all viruses in the ebolavirus genus, including their interactions with receptors in bats, their suspected reservoir hosts. These findings advance our understanding of ebolavirus cell entry, tissue tropism, and host range.

  PublisherDOI

• Insights into infraspecific differentiation of the medicinally important species Bupleurum Chinense revealed by morphological and molecular evidence

  BMC Plant Biology · 2025-05-13 · 1 citations

  articleOpen access1st authorCorresponding

  BACKGROUND: Radix Bupleuri, derived from the dried roots of Bupleurum chinense DC., is a well-documented phytomedicine in global pharmacopoeias and a common constituent in herbal formulations. While previous studies have hinted at regional variations in the chemical composition of B. chinense, a comprehensive understanding of its morphological, genetic, and chemical diversity across China remains incomplete. OBJECTIVE: This study aims to investigate the infraspecific variation of B. chinense by analyzing its morphological, genetic, and chemical phenotypes. METHODS: Wild B. chinense specimens were collected from 31 locations spanning nine Chinese provinces/municipalities, representing a wide range of its natural distribution. A multi-faceted approach combining 21 morphological traits, plastid genome sequencing, and chemical analysis was employed to explore infraspecific variation and clustering patterns. RESULTS: Distinct infraspecific variation was revealed through integrated morphological and molecular data. Morphological clustering analysis identified two geographically associated clusters, roughly corresponding to coastal and inland regions. Although plastid genome sequencing of 40 specimens showed high sequence identity, population structure analysis detected variable hotspots. Both maximum likelihood (ML) tree and population structure results consistently identified three distinct clades, which mirrored the patterns observed in morphological clustering. Quantitative analysis of saikosaponins content in 10 representative specimens across the three clades demonstrated significant chemotype variation. Notably, samples from Anhui Province exhibited the highest saikosaponins content, while those from Shanxi Province showed the lowest levels. This chemotype variation, coupled with observed genetic diversity, suggests that B. chinense germplasm from Clade I (particularly from Anhui Province) represents a promising wild resource for further development.

  PublisherOA PDFDOI

• <scp>METTL3</scp>‐Mediated <scp>m6A</scp> Modification of <scp>ISG15 mRNA</scp> Regulates Doxorubicin‐Induced Endothelial Cell Apoptosis

  Journal of Cellular and Molecular Medicine · 2025-01-01 · 4 citations

  articleOpen access

  N6-adenosine methylation (m6A) of RNA is involved in the regulation of various diseases. However, its role in chemotherapy-related vascular endothelial injury has not yet been elucidated. We found that methyltransferase-like 3 (METTL3) expression was significantly reduced during doxorubicin (DOX)-induced apoptosis of vascular endothelial cells both in vivo and in vitro, and that silencing of METTL3 further intensified this process. Combined transcriptome and proteome sequencing analyses revealed that the expression levels of interferon-stimulated gene 15 (ISG15) mRNA and protein significantly increased after METTL3 silencing. Methylated RNA immunoprecipitation (meRIP)-quantitative polymerase chain reaction (qPCR) and mRNA stability assays confirmed that METTL3 regulates the expression of ISG15 by methylating the 1,014,147 site on ISG15 RNA, thereby decreasing ISG15 mRNA levels. Silencing ISG15 significantly suppressed DOX-induced endothelial cell apoptosis and dysfunction caused by METTL3 silencing. In summary, our study revealed that METTL3-mediated methylation of ISG15 mRNA is involved in DOX-induced endothelial cell apoptosis and explored potential therapeutic targets for alleviating chemotherapy-associated vascular injury.

  PublisherOA PDFDOI

• Comparative Chloroplast Genome Analysis of Bupleurum sikangense and Its Allied Species Revealed An Efficient SCAR Marker For Its Identification

  Chiang Mai Journal of Science · 2025-05-16

  article

  Bupleurum sikangense, a new species discovered in 2011, is abundant in the Hengduan Mountains of China, and has the potential for a new origin of the crude drug Chaihu (Radix Bupleuri). A convenient method is therefore desired to differentiate it from the allied species. In this study, we found a unique insertion (AAATATCCTACATA) in B. sikangense by comparing its whole chloroplast genome with those of the other twenty-one Bupleurum species and based upon the insertion we designed a pair of species-specific primers (sxkF/R). With the primers, we established a sequence characterized amplified region (SCAR) detection method, which reached a successful rate of 100% in identifying B. sikangense, providing a useful tool for its further exploitation.

  PublisherDOI

• Long‐Circulating Nanobody Confers Durable Prophylaxis against Severe Acute Respiratory Syndrome Coronavirus 2 Omicron Infection

  Advanced NanoBiomed Research · 2025-06-27 · 1 citations

  articleOpen accessCorresponding

  Breakthrough infections in vaccinated population and continuous emergence of severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) variants make it imperative to develop more efficacious medical countermeasures. Previously, an anti‐SARS‐CoV‐2 nanobody, Nanosota‐3A, that neutralizes the infection of live Omicron BA.1 with picomolar potency, is identified. Herein, Nanosota‐3A is fused with the crystallizable fragment (Fc) domain of human IgG1 that contains M252Y/S254T/T256E (YTE) substitutions, named Nanosota‐3A‐Fc‐YTE. Compared to Nanosota‐3A‐Fc, Nanosota‐3A‐Fc‐YTE exhibits identical binding to the SARS‐CoV‐2 spike protein yet displays eightfold higher binding affinity for human neonatal Fc receptor (hFcRn) at pH 6.0. In hFcRn transgenic mice, the half‐life of Nanosota‐3A‐Fc and Nanosota‐3A‐Fc‐YTE is 5.1 days and 24.8 days, respectively. The mice are challenged with intranasal exposure of Omicron B.1.1.529 virus 55 days after a single dose of Nanosota‐3A fusions (20 mg kg −1 ) is administered. Compared to the untreated controls, the lung viral titers in mice receiving Nanosota‐3A‐Fc‐YTE are reduced by 104.7‐fold ( p = 0.007) with 50% of the mice free of detectable virus. By contrast, Nanosota‐3A‐Fc‐treated mice show only 3.5‐fold reduction in the viral titers ( p = 0.41). The durable protection conferred by a single dose of Nanosota‐3A‐Fc‐YTE administered nearly 2 months prior to the virus exposure demonstrates the promise of long‐circulating nanobodies as powerful prophylactics against SARS‐CoV‐2.

  PublisherOA PDFDOI

• Analysis of histone modifications in key cellular subpopulations in the context of azoospermia using spermatogenic single-cell RNA-seq data

  Frontiers in Bioinformatics · 2025-07-18

  articleOpen access

  Introduction: The molecular underpinnings of non-obstructive azoospermia (NOA), a severe form of male infertility characterized by the absence of sperm in the ejaculate, remain unclear. Methods: In this study, we demonstrate the role of histone modifications within specific testicular cell subpopulations in NOA using single-cell RNA sequencing (scRNA-seq) data. Results: Based on scRNA-seq analysis of the data acquired from the Gene Expression Omnibus (GSE149512), we identified nine distinct cell types and revealed significant compositional differences between the NOA and control testicular tissues. In contrast to the high prevalence of spermatogenic cells in the controls, endothelial, testicular interstitial, and vascular smooth muscle cells, as well as macrophages, were enriched in NOA. Furthermore, our analyses revealed considerable enrichment of histone modificationrelated genes in Leydig cells, peritubular myoid (PTM) cells, and macrophages in the NOA group. HDAC2, a pivotal regulator of histone acetylation, exhibited significant upregulation. Functional pathway analysis implicated these genes in critical biological processes, including nuclear transport, RNA splicing, and autophagy. We quantified the activity of histone modificationrelated genes using AUCell and identified distinct Leydig cell subpopulations characterized by unique marker genes and functional pathways, underscoring their dual roles in histone modification and spermatogenesis. Additionally, cellular communication analysis via CellChat demonstrated altered interaction dynamics across cell types in NOA, particularly in Leydig and PTM cells, which exhibited enhanced interactions alongside differential activation of the WNT and NOTCH signaling pathways. Discussion: These findings suggest that aberrant histone modifications in specific cellular subpopulations may drive disease progression, highlighting potential targets for diagnostic and therapeutic strategies. This study offers novel insights into the molecular mechanisms of NOA and provides a basis for future research on advanced male reproductive health.

  PublisherDOI

• Enhancing Point-of-Care Diagnosis of African Swine Fever Virus (ASFV) DNA with the CRISPR-Cas12a-Assisted Triplex Amplified Assay

  Analytical Chemistry · 2024-03-19 · 20 citations

  article

  Accurate, ultrasensitive, and point-of-care (POC) diagnosis of the African swine fever virus (ASFV) remains imperative to prevent its spread and limit the losses incurred. Herein, we propose a CRISPR-Cas12a-assisted triplex amplified colorimetric assay for ASFV DNA detection with ultrahigh sensitivity and specificity. The specific recognition of recombinase aided amplification (RAA)-amplified ASFV DNA could activate the Cas12a/crRNA/ASFV DNA complex, leading to the digestion of the linker DNA (bio-L1) on magnetic beads (MBs), thereby preventing its binding of gold nanoparticles (AuNPs) network. After magnetic separation, the release of AuNPs network comprising a substantial quantity of AuNPs could lead to a discernible alteration in color and significantly amplify the plasmonic signal, which could be read by spectrophotometers or smartphones. By combining the RAA, CRISPR/Cas12a-assisted cleavage, and AuNPs network-mediated colorimetric amplification together, the assay could detect as low as 0.1 copies/μL ASFV DNA within 1 h. The assay showed an accuracy of 100% for the detection of ASFV DNA in 16 swine tissue fluid samples, demonstrating its potential for on-site diagnosis of ASFV.

  PublisherDOI

• Dual-role epitope on SARS-CoV-2 spike enhances and neutralizes viral entry across different variants

  PLoS Pathogens · 2024-09-05 · 6 citations

  articleOpen accessSenior author

  Grasping the roles of epitopes in viral glycoproteins is essential for unraveling the structure and function of these proteins. Up to now, all identified epitopes have been found to either neutralize, have no effect on, or enhance viral entry into cells. Here, we used nanobodies (single-domain antibodies) as probes to investigate a unique epitope on the SARS-CoV-2 spike protein, located outside the protein's receptor-binding domain. Nanobody binding to this epitope enhances the cell entry of prototypic SARS-CoV-2, while neutralizing the cell entry of SARS-CoV-2 Omicron variant. Moreover, nanobody binding to this epitope promotes both receptor binding activity and post-attachment activity of prototypic spike, explaining the enhanced viral entry. The opposite occurs with Omicron spike, explaining the neutralized viral entry. This study reveals a unique epitope that can both enhance and neutralize viral entry across distinct viral variants, suggesting that epitopes may vary their roles depending on the viral context. Consequently, antibody therapies should be assessed across different viral variants to confirm their efficacy and safety.

  PublisherDOI

• Pan-beta-coronavirus subunit vaccine prevents SARS-CoV-2 Omicron, SARS-CoV, and MERS-CoV challenge

  Journal of Virology · 2024-08-27 · 15 citations

  articleOpen access

  Three highly pathogenic coronaviruses (CoVs), SARS-CoV-2, SARS-CoV, and MERS-CoV, belonging to the genus beta-CoV, have caused outbreaks or pandemics. SARS-CoV-2 has evolved into many variants with increased resistance to the current vaccines. Spike (S) protein and its receptor-binding domain (RBD) fragment of these CoVs are important vaccine targets; however, the RBD of the SARS-CoV-2 Omicron variant is highly mutated, rending neutralizing antibodies elicited by ancestral-based vaccines targeting this region ineffective, emphasizing the need for effective vaccines with broad-spectrum efficacy against SARS-CoV-2 variants and other CoVs with pandemic potential. This study describes a pan-beta-CoV subunit vaccine, Om-S-MERS-RBD, by fusing the conserved and highly potent RBD of MERS-CoV into an RBD-truncated SARS-CoV-2 Omicron S protein, and evaluates its neutralizing immunogenicity and protective efficacy in mouse models. Om-S-MERS-RBD formed a conformational structure, maintained effective functionality and antigenicity, and bind efficiently to MERS-CoV receptor, human dipeptidyl peptidase 4, and MERS-CoV RBD or SARS-CoV-2 S-specific antibodies. Immunization of mice with Om-S-MERS-RBD and adjuvants (Alum plus monophosphoryl lipid A) induced broadly neutralizing antibodies against pseudotyped MERS-CoV, SARS-CoV, and SARS-CoV-2 original strain, as well as T-cell responses specific to RBD-truncated Omicron S protein. Moreover, the neutralizing activity against SARS-CoV-2 Omicron subvariants was effectively improved after priming with an Omicron-S-RBD protein. Adjuvanted Om-S-MERS-RBD protein protected mice against challenge with SARS-CoV-2 Omicron variant, MERS-CoV, and SARS-CoV, significantly reducing viral titers in the lungs. Overall, these findings indicated that Om-S-MERS-RBD protein could develop as an effective universal subunit vaccine to prevent infections with MERS-CoV, SARS-CoV, SARS-CoV-2, and its variants. IMPORTANCE: Coronaviruses (CoVs), SARS-CoV-2, SARS-CoV, and MERS-CoV, the respective causative agents of coronavirus disease 2019, SARS, and MERS, continually threaten human health. The spike (S) protein and its receptor-binding domain (RBD) fragment of these CoVs are critical vaccine targets. Nevertheless, the highly mutated RBD of SARS-CoV-2 variants, especially Omicron, significantly reduces the efficacy of current vaccines against SARS-CoV-2 variants. Here a protein-based pan-beta-CoV subunit vaccine is designed by fusing the potent and conserved RBD of MERS-CoV into an RBD-truncated Omicron S protein. The resulting vaccine maintained effective functionality and antigenicity, induced broadly neutralizing antibodies against all of these highly pathogenic human CoVs, and elicited Omicron S-specific cellular immune responses, protecting immunized mice from SARS-CoV-2 Omicron, SARS-CoV, and MERS-CoV infections. Taken together, this study rationally designed a pan-beta-CoV subunit vaccine with broad-spectrum efficacy, which has the potential for development as an effective universal vaccine against SARS-CoV-2 variants and other CoVs with pandemic potential.

  PublisherOA PDFDOI

Recent grants

• Novel nanobodies to prevent and treat SARS-CoV-2 and other pathogenic human coronaviruses

  NIH · $3.9M · 2020–2026

• Receptor recognition and cell entry of coronaviruses

  NIH · $4.1M · 2010–2021

• Cell entry, cross-species transmission and pathogenesis of novel coronavirus from

  NIH · $7.4M · 2015–2025

Frequent coauthors

• Jincun Zhao

  Guangzhou Medical University

  42 shared

• Gang Ye

  University of Minnesota

  41 shared

• Zhen Zhuang

  State Key Laboratory of Respiratory Disease

  36 shared

• Jing Sun

  State Key Laboratory of Respiratory Disease

  36 shared

• Lanying Du

  Georgia State University

  35 shared

• Airu Zhu

  State Key Laboratory of Respiratory Disease

  27 shared

• Fan Bu

  Hormel (United States)

  27 shared

• Mian Gan

  First Affiliated Hospital of Guangzhou Medical University

  27 shared

Labs

• Laboratory of Structural Biology of DiseasePI