About

Professor Jieli (Shirley) Li is not explicitly described in the provided page text. The page primarily lists team members, including faculty, research scientists, graduate researchers, undergraduate researchers, and past members, but does not include a specific biography or research focus for Professor Li.

Research topics

• Biology
• Virology
• Chemistry
• Biochemistry
• Medicine
• Genetics
• Political Science
• Ecology
• Immunology
• Internal medicine
• Microbiology
• Zoology
• Food science
• Law
• Computational biology
• Molecular biology

Selected publications

• Integrative Analysis Reveals the Prognostic Effects of Epigenetic Regulators in Bladder Cancer

  Cancer Medicine · 2025-07-01 · 3 citations

  articleOpen access

  BACKGROUND: Epigenetic regulatory genes (epiRG) are pivotal in the epigenetic regulation of the human genome, primarily through DNA and histone modifications. These genes are frequently mutated in human cancers, particularly bladder cancer (BC). However, the functional impact of epiRG mutations on patient outcomes remains poorly understood. METHODS: In this study, we developed gene signatures for the most frequent genomic aberrations of epiRG using The Cancer Genome Atlas Bladder Carcinoma (TCGA-BLCA) dataset and validated these signatures with independent tumor expression profiles for prognostic relevance. Furthermore, we evaluated the role of these signature scores in the immune system within the tumor microenvironment (TME). Finally, we assessed the correlation between epiRG and global DNA methylation. RESULTS: Our results indicated that the inferred aberration-specific signature scores were more predictive of patient stratification than the genomic aberrations. Notably, certain signature scores were significantly associated with patient progression, whereas others correlated with the tumor immune microenvironment via interactions with the immune system. Patients with mutations had high signature scores in CREBBP-mut and EP300-mut, which revealed poor overall survival. Conversely, KDM6A-mut signatures showed an opposite trend, with low scores linking to favorable prognosis through enhanced immune activity. Also, other epiRG signature scores were strongly correlated with the immune system in TME and successfully predicted patients who responded to immunotherapy. Global methylation analysis revealed that high signature scores of KDM6A-mut are associated with hypomethylation. CONCLUSIONS: These findings collectively establish epiRG signature scores as powerful biomarkers that integrate genomic, epigenetic, and immune microenvironment features for improved prognostic prediction in bladder cancer. This integrative approach not only advances our understanding of epigenetic mechanisms in BC but also offers potential for developing innovative prognostic tools and therapeutic strategies tailored to personalized medicine.

  PublisherOA PDFDOI

• Neutralization and spike stability of JN.1-derived LB.1, KP.2.3, KP.3, and KP.3.1.1 subvariants

  mBio · 2025-03-26 · 20 citations

  articleOpen access

  During the summer of 2024, coronavirus disease 2019 (COVID-19) cases surged globally, driven by variants derived from JN.1 subvariants of severe acute respiratory syndrome coronavirus 2 that feature new mutations, particularly in the N-terminal domain (NTD) of the spike protein. In this study, we report on the neutralizing antibody (nAb) escape, infectivity, fusion, and spike stability of these subvariants-LB.1, KP.2.3, KP.3, and KP.3.1.1. Our findings demonstrate that all of these subvariants are highly evasive of nAbs elicited by the bivalent mRNA vaccine, the XBB.1.5 monovalent mumps virus-based vaccine, or from infections during the BA.2.86/JN.1 wave. This reduction in nAb titers is primarily driven by a single serine deletion (DelS31) in the NTD of the spike, leading to a distinct antigenic profile compared to the parental JN.1 and other variants. We also found that the DelS31 mutation decreases pseudovirus infectivity in CaLu-3 cells, which correlates with impaired cell-cell fusion. Additionally, the spike protein of DelS31 variants appears more conformationally stable, as indicated by reduced S1 shedding both with and without stimulation by soluble ACE2 and increased resistance to elevated temperatures. Molecular modeling suggests that DelS31 enhances the NTD-receptor-binding domain (RBD) interaction, favoring the RBD down conformation and reducing accessibility to ACE2 and specific nAbs. Moreover, DelS31 introduces an N-linked glycan at N30, shielding the NTD from antibody recognition. These findings underscore the role of NTD mutations in immune evasion, spike stability, and viral infectivity, highlighting the need to consider DelS31-containing antigens in updated COVID-19 vaccines.IMPORTANCEThe emergence of novel severe acute respiratory syndrome coronavirus 2 variants continues to pose challenges for global public health, particularly in the context of immune evasion and viral stability. This study identifies a key N-terminal domain (NTD) mutation, DelS31, in JN.1-derived subvariants that enhances neutralizing antibody escape while reducing infectivity and cell-cell fusion. The DelS31 mutation stabilizes the spike protein conformation, limits S1 shedding, and increases thermal resistance, which possibly contribute to prolonged viral persistence. Structural analyses reveal that DelS31 enhances NTD-receptor-binding domain interactions by introducing glycan shielding, thus decreasing antibody and ACE2 accessibility. These findings emphasize the critical role of NTD mutations in shaping viral evolution and immune evasion, underscoring the urgent need for updated coronavirus disease 2019 vaccines that account for these adaptive changes.

  PublisherDOI

• Prolonging lung cancer response to EGFR inhibition by targeting the selective advantage of resistant cells

  Nature Communications · 2025-08-22 · 1 citations

  articleOpen access

  Non-small cell lung cancers (NSCLCs) treated with tyrosine kinase inhibitors (TKIs) of the epidermal growth factor receptor (EGFR) almost invariably relapse in the long term, due to the emergence of subpopulations of resistant cells. Through a DNA barcoding approach, we show that the clinically approved drug sorafenib specifically abolishes the selective advantage of EGFR-TKI-resistant cells, while preserving the response of EGFR-TKI-sensitive cells. Sorafenib is active against multiple mechanisms of resistance/tolerance to EGFR-TKIs and its effects depend on early inhibition of MAPK-interacting kinase (MKNK) activity and signal transducer and activator of transcription 3 (STAT3) phosphorylation, and later down-regulation of MCL1 and EGFR. Using different xenograft and allograft models, we show that the sorafenib-EGFR-TKI combination can delay tumor growth and promote the recruitment of inflammatory cells. Together, our findings indicate that sorafenib can prolong the response to EGFR-TKIs by targeting NSCLC capacity to adapt to treatment through the emergence of resistant cells.

  PublisherOA PDFDOI

• Annual (2024) taxonomic update of RNA-directed RNA polymerase-encoding negative-sense RNA viruses (realm Riboviria: kingdom Orthornavirae: phylum Negarnaviricota)

  Journal of General Virology · 2025-06-13 · 6 citations

  articleOpen access

  In April 2024, following the annual International Committee on Taxonomy of Viruses (ICTV) ratification vote on newly proposed taxa, the phylum Negarnaviricota was expanded by 1 new order, 1 new family, 6 new subfamilies, 34 new genera and 270 new species. One class, two orders and six species were renamed. Seven families and 12 genera were moved; ten species were renamed and moved; and nine species were abolished. This article presents the updated taxonomy of Negarnaviricota as currently accepted by the ICTV, providing an essential annual update on the classification of members of this phylum that deepen understandings of their evolution, and supports critical public health measures for virus identification and tracking.

  PublisherDOI

• Promotion of HIV clearance by sensitization of HIV reservoirs to cell death

  Frontiers in Immunology · 2025-07-14

  articleOpen access

  Introduction: HIV integrates its proviral DNA into the host genome to establish persistent infection. To promote HIV clearance, we have designed an approach for selective elimination of host cells harboring replication-competent HIV (SECH), through inhibition of autophagy and anti-apoptotic molecules during viral reactivation. SECH approach can clear HIV-infected cells in approximately 50% humanized mice. However, the mechanisms for the resistance of reservoirs to depletion in mice with failure in HIV clearance are unclear. Methods: We have performed single cell transcriptome analyses of HIV-infected T cells that escaped the treatments, in order to identify cellular pathways that could be targeted to facilitate the deletion of refractory HIV reservoirs. Results: By single cell RNA sequencing analyses of T cell reservoirs resistant to SECH treatments, we found increases in pro-survival autophagy and glycolysis. Moreover, these resistant reservoirs expressed more epigenetic modifiers that repress HIV gene expression, while targeting such epigenetic repression promoted cell death in HIV-infected cells. Discussion: Our results indicate that T cell reservoirs refractory to depletion maintain a delicate balance between low levels of HIV gene expression and evasion of cell death. This study suggests that targeting epigenetic repression of HIV is critical for the depletion of the viral reservoirs.

  PublisherOA PDFDOI

• Intranasal measles virus- and mumps virus-based SARS-CoV-2 vaccine candidates prevent SARS-CoV-2 infection and transmission.

  PubMed · 2025-08-12 · 1 citations

  articleOpen accessSenior author

  mice. Finally, intranasal immunization with the trivalent vaccine efficiently blocked transmission of SARS-CoV-2 WA1 and Omicron XBB.1.5 among hamsters in a direct contact transmission setting. In summary, we have developed intranasal MeV and MuV-based trivalent vaccines that induce broad NAbs, robust mucosal immunity, and strong protection against both virus challenge and virus transmission.

  PublisherOA PDFDOI

• Spatial and multiomics analysis of human and mouse lung adenocarcinoma precursors reveals TIM-3 as a putative target for precancer interception

  Cancer Cell · 2025-05-08 · 26 citations

  articleOpen access

  How tumor microenvironment shapes lung adenocarcinoma (LUAD) precancer evolution remains poorly understood. Spatial immune profiling of 114 human LUAD and LUAD precursors reveals a progressive increase of adaptive response and a relative decrease of innate immune response as LUAD precursors progress. The immune evasion features align the immune response patterns at various stages. TIM-3-high features are enriched in LUAD precancers, which decrease in later stages. Furthermore, single-cell RNA sequencing (scRNA-seq) and spatial immune and transcriptomics profiling of LUAD and LUAD precursor specimens from 5 mouse models validate high TIM-3 features in LUAD precancers. In vivo TIM-3 blockade at precancer stage, but not at advanced cancer stage, decreases tumor burden. Anti-TIM-3 treatment is associated with enhanced antigen presentation, T cell activation, and increased M1/M2 macrophage ratio. These results highlight the coordination of innate and adaptive immune response/evasion during LUAD precancer evolution and suggest TIM-3 as a potential target for LUAD precancer interception. • Coordinated innate and adaptive immune response shapes lung precancer evolution • Lung adenocarcinoma precursors have stage-specific tumor microenvironment • Upregulation of TIM-3 plays a critical role in lung precancer progression • TIM-3 blockade inhibits progression of precancer but not established lung cancer Zhu et al. reveal coordinated interplay between innate and adaptive immunity in the transition from precancer to invasive lung cancer. TIM-3 upregulation peaks at precancer stage and its blockade enhances anti-tumor immunity while inhibiting lung precancer progression, suggesting TIM-3 as a potential target for lung precancer interception.

  PublisherDOI

• Caspase-11 Mediated Hyperinflammation Impairs CD8⁺ T Cell Immunity and Viral Clearance in Severe SARS-CoV-2 Infection

  bioRxiv (Cold Spring Harbor Laboratory) · 2025-11-03

  preprintOpen access

  Abstract Severe SARS-CoV-2 infection is characterized by lung hyperinflammation, impaired interferon responses, and defective T-cell activation, yet the molecular drivers of these immune dysregulations remain incompletely understood. Caspase-11 (CASP11), a key mediator of the non-canonical inflammasome, has been shown to mediate an innate hyperinflammatory response and cytokine release in a non-severe, non-lethal SARS-CoV-2 infection model. However, the role played by CASP11 in severe SARS-CoV-2 disease and how it impacts adaptive immunity is not identified. Here, we newly discover that CASP11 exacerbates severe SARS-CoV-2 pathogenesis by amplifying early innate immune responses while concurrently impairing antiviral CD8 T-cell immunity. Using global knockouts, reciprocal bone marrow chimeras, and phagocyte-monocyte system (PMS) cell-specific CASP11 deletion models, we show that CASP11 deletion in monocyte-derived cells reduces lung inflammation, enhances type I and II interferon signaling, and promotes robust virus-specific effector CD8⁺ T-cell response. This was associated with enhanced viral clearance and improved survival, even under lethal infection conditions. Importantly, CASP11 KO mice also exhibited faster resolution of post-viral inflammation, suggesting a role in long-term immune remodeling. These findings position CASP11 as a promising immunomodulatory target for acute and delayed manifestations of severe SARS-CoV-2.

  PublisherOA PDFDOI

• Intranasal co-delivery of measles virus and mumps virus expressing nucleocapsid and prefusion spike proteins enhances protection against SARS-CoV-2 infection 2659

  The Journal of Immunology · 2025-11-01

  articleOpen accessSenior author

  Abstract Description While current SARS-CoV-2 vaccines have lowered the risk of death associated with COVID-19 disease, SARS-CoV-2 continues to mutate leading to new Variants of Concern (VoC). These mutations, focused in the S protein, can often lead to immune evasiveness, leaving current vaccines ineffective and leading to more investigation of more conserved proteins as potential antigens such as the nucleocapsid (N). In this study, we generated a bivalent live attenuated virus using mumps (MuV) Jeryl Lynn 2 (JL2) strain as a viral vector to express the N protein in combination with MuV-JL2 expressing WA1, the ancestral strain of SARS-CoV-2, or MuV-JL1 expressing XBB 1.5 spike protein stabilized by 6 prolines. The MuV-JL2-N co-delivered with MuV-JL2-WA1 was not only able to induce high anti-N and anti-WA1 S-specific antibodies but also resident memory T cells in the lungs of immunized IFNAR-/- mice. When MuV-JL2-N was co-delivered intranasally with MuV-JL1-XBB 1.5 in golden Syrian hamsters, hamsters could also induce high anti-N and anti-S XBB 1.5 IgG antibodies. When challenged against the Omicron JN.1 variant, hamsters immunized with the bivalent vaccine exhibited no viral titer in the lungs as opposed to hamsters immunized with either MuV-JL2-N and MuV-JL1-XBB 1.5 monovalent vaccines, which had an average viral titer of log 4.7 and log 3.5, respectively. Therefore, co-delivery of MuV-JL2-N and MuV-JL1-XBB 1.5 intranasally enhances protection against SARS-CoV-2 variants such as JN.1. Funding Sources NIH GR135608 Topic Categories Vaccines and Immunotherapy (VAC)

  PublisherOA PDFDOI

• Efficacy and safety of trastuzumab deruxtecan for metastatic HER2+ and HER2-low breast cancer: A systematic review and meta-analysis

  Medicine · 2025-11-14 · 1 citations

  articleOpen access

  BACKGROUND: Trastuzumab deruxtecan (T-DXd) is a novel antibody-drug conjugate uesd for the treatment of HER2- positive (HER2+)breast cancer. This systematic review aimed to evaluate the efficacy and safety of T-DXd in advanced HER2-positive breast cancer. METHODS: PubMed, Web of Science and Embase databases were searched for literature on trastuzumab deruxtecan treatment for HER2-positive or low-expression breast cancer before December 30, 2024. The outcome measures were progression-free survival (PFS), overall survival (OS), objective response rates, and adverse events of any grade and grade ≥ 3. Meta-analysis of the relevant data was performed using Stata 14.0. RESULTS: A total of 2995 patients from 7 studies were included. The median PFS and median overall survival of patients in the T-DXd group were significantly longer than those of patients in the control group (mPFS HR = 0.43;95% CI:0.31-0.62, p<0.05; mOS HR = 0.72; 95% CI:0.64-0.82, p<0.05). Further subgroup analyses based on differences in hormone receptor expression, occurrence of brain metastases, visceral basal conditions, and previous lines of treatment showed that all patients in the T-DXd group had significantly longer mPFS than those in the control group (P < .05). The objective remission rate of patients in the T-DXd group was significantly higher than that of patients in the control group (RR = 2.31; 95%CI: 1.88-2.85, P<0.05). In addition, the T-DXd also increased the incidence of adverse events such as anemia, nausea, vomiting, constipation and interstitial lung disease, but the incidence of neutropenia, diarrhea, and alopecia was not significantly different between the 2 groups. No significant publication bias was observed in this study. The results of the sensitivity analysis showed high heterogeneity in mPFS, but the results obtained after excluding the DESTINY-Breast04 studies were all more robust. CONCLUSION: T-DXd has significant long-term and near-term efficacy in prolonging median overall survival, median PFS, and increasing the objective remission rate in patients with HER2-positive or low-expression breast cancer; however, the treatment is associated with notable adverse events, and physicians should be alert to the occurrence of serious adverse events when using this drug.

  PublisherDOI

Recent grants

• NIH Grant P01AI112524

  NIH · $13.3M · 2021

• Messenger RNA capping and methylation in pneumoviruses

  NIH · $4.0M · 2010–2025

• A novel lactic acid bacteria-based norovirus vaccine

  NIH · $3.0M · 2016–2023

• NIH Grant R56AI090060

  NIH · $373k · 2010

Frequent coauthors

• Mark E. Peeples

  47 shared

• Mijia Lu

  The Ohio State University

  35 shared

• Yuanmei Ma

  The Ohio State University

  27 shared

• Lizhong Sun

  25 shared

• Xueya Liang

  Lanzhou University

  24 shared

• Dao-Xin Wang

  Second Affiliated Hospital of Chongqing Medical University

  17 shared

• Tian-wen Guang

  Chongqing Medical University

  17 shared

• Faguo Wang

  South China Botanical Garden

  16 shared

Labs

• AI4PathPI

  From Pixels to Prognosis: AI in Action!

Education

• M.D., Clinical Medicine

  Shanghai Jiao-Tong University School of Medicine, China

  2002

• Ph.D., Endocrinology

  Shanghai Jiao-Tong University School of Medicine, China

  2009

• Other

  Department of Medical Physiology, Texas A&M University Health Science Center

  2009

• Other

  Department of Physiology and Biophysics, University of Illinois at Chicago

  2011

• Other

  Department of Pathology, University of Texas MD Anderson Cancer Center

  2017