About

Jie Zheng is a Professor-in-Residence in the Department of Ophthalmology at the University of California, Los Angeles (UCLA). His research focuses on characterizing the expression profile of Dexras1 in human trabecular meshwork cells, investigating extracellular vesicles derived from corneal stromal stem cells and their effects on ANGPTL7 expression, and advancing the diagnosis and management of limbal stem cell deficiency. Zheng's work also includes studying the activation and therapeutic potential of Wnt proteins, as well as exploring metabolic profiles of trabecular meshwork cells treated with dexamethasone. His contributions extend to structural and functional insights into protein interactions relevant to cell adhesion and signaling pathways, as well as drug discovery efforts targeting Wnt signaling pathways. Zheng has authored numerous publications in the fields of biochemistry, cell biology, and vision science, emphasizing his expertise in molecular mechanisms underlying ocular health and disease.

Research topics

• Biology
• Chemistry
• Cell biology
• Medicine
• Biochemistry

Selected publications

• A novel mechanism of chlorogenic acid against type 2 diabetes-induced diabetic retinopathy: suppressing ferroptosis via NRF2/xCT/GPX4 and STAT3 signaling

  Naunyn-Schmiedeberg s Archives of Pharmacology · 2026-02-23

  article1st author
  PublisherDOI

• Transcriptional coordination in multicellular lineage differentiation during lung organogenesis: deciphering the role of epithelial cells as a microenvironmental regulatory hub

  Frontiers in Cell and Developmental Biology · 2026-02-20

  articleOpen access

  Lung development is a complex and precisely regulated process of continuously branching morphogenesis, the core of which lies in the directed differentiation of diverse cell types and the dynamic intercellular interaction network. This review systematically delineates the differentiation pathways of major cellular lineages during pulmonary development, with a particular focus on the dual functions of epithelial cells as the core regulatory hub of the microenvironment. These cells not only dominate the spatial patterning of lung branching morphogenesis but also orchestrate the developmental fates of key cell types through multiple signaling cues. Furthermore, this review discusses the regenerative properties of lung-resident stem cells and the interaction patterns between various cell types and epithelial cells. These insights not only provide an important theoretical framework for elucidating the molecular regulatory network of lung development but also offer novel ideas for the optimization of strategies in lung regenerative medicine and the precision intervention for lung-related diseases.

  PublisherDOI

• Dishevelled PDZ domain targeting peptides modulate non-canonical Wnt5a/Ror signaling

  Biochemistry and Biophysics Reports · 2026-05-01

  articleOpen accessSenior author

  Dishevelled (Dvl) is a highly conserved scaffolding protein that plays a key role in the non-canonical Wnt signaling pathway. However, the exact mechanisms by which Dvl modulates pathway activation are not fully understood. The C-terminus of Dvl binds intramolecularly to its PDZ domain, stabilizing Dvl in an autoinhibited, closed state. To evaluate the importance of this intramolecular interaction, we used PDZ-binding peptides to disrupt the autoinhibitory binding. We found that these peptides activated non-canonical Wnt5a/Ror signaling. However, this effect was weaker than that of Wnt5a, suggesting that other factors likely contribute to the full signaling response. Additionally, these PDZ-binding peptides affected Wnt5a-induced signaling, suggesting the significance of Dvl's intermolecular interactions in determining signaling outcomes. Given the wide range of intracellular proteins that interact with the Dvl PDZ domain, these proteins can regulate Wnt signaling by controlling the transition from an inactive, closed state to an open, and possibly active, state.

  PublisherDOI

• Computational Binding Affinities of Disheveled PDZ Protein-Ligand Complexes

  bioRxiv (Cold Spring Harbor Laboratory) · 2025-09-21

  preprintOpen accessSenior author

  ABSTRACT Wnt/ß-catenin signaling is critical for cell growth and development, with its hyperactive dysregulation implicated in the development of cancer. Current therapeutic research on inhibition of Wnt/ß-catenin signaling is impeded by the high cost of experimentally determining binding affinities. Consequently, interest has risen in screening potential inhibitors binding affinities with computational tools to reduce costs. Here, we test the validity of a computational molecular dynamics simulator, Binding Free Energy Estimator 2 (BFEE2), for determining peptide ligand affinity for Wnt/ß-catenin signaling. We focus on the Dishevelled (DVL) PDZ domain, a key mediator in WNT signaling through its ability to bind to various peptide ligands. We analyze the binding affinities of several DVL PDZ domain-peptide and domain-ligand complexes against previously established results to determine the validity of computational analysis. We conclude that computational molecular dynamics simulations were successful for peptide-ligand complexes with mixed results for small-molecule scenarios.

  PublisherOA PDFDOI

• Corneal Stromal Stem Cell-Derived Extracellular Vesicles Attenuate ANGPTL7 Expression in the Human Trabecular Meshwork

  Translational Vision Science & Technology · 2025-01-23 · 1 citations

  articleOpen accessSenior authorCorresponding

  Purpose: Regulating intraocular pressure (IOP), mainly via the trabecular meshwork (TM), is critical in developing glaucoma. Whereas current treatments aim to lower IOP, directly targeting the dysfunctional TM tissue for therapeutic intervention has proven challenging. In our study, we utilized Dexamethasone (Dex)-treated TM cells as a model to investigate how extracellular vesicles (EVs) from immortalized corneal stromal stem cells (imCSSCs) could influence ANGPTL7 and MYOC genes expression within TM cells. Methods: Human TM cell lines were isolated and cultured from donor corneoscleral rims. EVs were purified from imCSSC conditioned media (CM) using size exclusion chromatography and characterized by nanoparticle tracking analysis, transmission electron microscopy (TEM), and ExoView technology. TM cells were treated with either Dex alone or with EVs for 5 days. Quantitative polymerase chain reaction (PCR) was carried out to quantify the mRNA level of MYOC and ANGPTL7. Results: A notable increase in the expression levels of MYOC and ANGPTL7 genes was observed compared with untreated TM cells (control). Furthermore, upon comparing Dex-treated TM cells with those receiving both Dex and EV treatments, a statistically significant reduction in ANGPTL7 expression (P < 0.05) was detected. Conclusions: The present study demonstrates that imCSSCs-derived EVs can effectively decrease the expression of ANGPLT7, a gene associated with fibrosis and implicated in the abnormal elevation of IOP in patients with glaucoma. Translational Relevance: Our study shows that imCSSC-derived EVs can specifically target ANGPTL7 expression, making them a promising preclinical therapy for glaucoma.

  PublisherOA PDFDOI

• Optimizing the Food–Energy–Water Nexus: A Multi-Objective Spatial Configuration Framework for High-Density Communities

  Buildings · 2025-06-23

  articleOpen access1st author

  Global urbanization and climate change are intensifying challenges in the sustainable management of the Food–Energy–Water (FEW) system. This study introduces a multi-objective optimization framework that redefines urban spaces through a dual rooftop-ground hierarchy, interlinkage nodes for mapping material and energy flows, and the application of NSGA-II optimization to balance food production, energy output, and costs. The framework was applied to a case study area, generating non-dominated solutions with diverse resource-cost configurations. The findings revealed that optimal scenarios could meet 40.6% of local energy demands and exceed 102.9% of local grain demands, while maintaining economic viability. This approach bridges resource systems theory and spatial planning practice, providing economically viable pathways for high-density cities to transform into hybrid production-consumption spaces, effectively addressing the dual pressures of urbanization and climate change.

  PublisherDOI

• Author response for "Co‐expression of &lt;scp&gt;HSV&lt;/scp&gt;‐1 &lt;scp&gt;ICP34&lt;/scp&gt;.5 enhances the expression of gene delivered by self‐amplifying &lt;scp&gt;RNA&lt;/scp&gt; and mitigates its immunogenicity"

  2025-03-11

  peer-review
  PublisherDOI

• Maternal behavior promotes resilience to adolescent stress in mice through a microglia-neuron axis

  Nature Communications · 2025-03-08 · 7 citations

  articleOpen access

  Early life experience modulates resilience to stress in later life. Previous research implicated maternal care as a key mediator of behavioral responses to the adversity in adolescence, but details of molecular mechanisms remain elusive. Here, we show social stress activates transcription factor C/EBPβ in mPFC neurons of adolescent mice, which transcriptionally upregulates Dnm1l and promotes mitochondrial dysfunction, thereby conferring stress susceptibility in adolescent mice. Moreover, different maternal separation differentially regulates adolescent stress susceptibility. Mechanistically, this differential effect depends on maternal behavior-stimulated IGF-1, which inhibits neuronal C/EBPβ through mTORC1-induced C/EBPβ-LIP translation. Furthermore, we identify maternal behavior-stimulated IGF-1 is mainly released from mPFC microglia. Notably, increased maternal care under an environmental enrichment condition or maternal behavior impairment induced by repeated MPOAEsr1+ cells inhibition in dams prevents or promotes stress susceptibility via microglial-to-neuronal IGF-1-C/EBPβ-DRP1 signaling. In this work, these findings have unveiled molecular mechanisms by which maternal behavior promotes stress resilience in adolescents. Early life experience modulates stress resilience in later life. Here the authors show that maternal care triggers microglia-derived IGF-1 levels, which suppresses the neuronal C/EBPβ-DRP1 axis, promoting stress resilience in adolescent mice.

  PublisherOA PDFDOI

• A multi-biomarker panel for non-invasive diagnosis, risk stratification, subtype identification, and therapeutic targeting in NAFLD: bioinformatics and experimental insights

  Biochemical and Biophysical Research Communications · 2025-07-23

  articleOpen accessCorresponding

  Non-alcoholic fatty liver disease (NAFLD) lacks reliable non-invasive diagnostic tools and effective therapeutic targets. This study aimed to identify serum biomarkers for diagnosis, risk stratification, and therapeutic targeting. Inflammation- and NET-related differentially expressed genes (INRDEGs) were screened from GEO datasets. LASSO/SVM regression constructed a diagnostic model, validated via ROC/calibration/decision curve analyses. Immune infiltration (CIBERSORT/ssGSEA), consensus clustering, and interaction networks (miRNA/TF/ drug) were employed. Hub genes were validated in diet-induced NASH mice. TNF, IL6, CCL5, and SPP1 were identified as key biomarkers. The diagnostic model achieved high accuracy (AUC=0.803) and enabled risk stratification: TNF, SPP1, and CCL5 marked high-risk patients, while IL6 dominated low-risk subgroups. Two NAFLD subtypes with distinct immune profile were classified. Key biomarkers were identified as potential therapeutic targets. Regulatory networks predicted repurposable drugs. Animal experiments confirmed elevated serum levels of these genes in NASH mice (p<0.001). This study establishesed TNF, IL6, CCL5, and SPP1 as a multi-functional biomarker panel for NAFLD, enabling non-invasive diagnosis, risk stratification, subtype classification, and target-specific therapy. These findings provide new insights for the management of NAFLD and a feasible theoretical basis for clinical translation. 1. TNF, IL6, CCL5, and SPP1 were served as non-invasive serum biomarkers for NAFLD diagnosis. 2. NAFLD Risk-stratification : Increased expression of TNF, SPP1, and CCL5 indicates high risk, while increased expression of IL6 indicates relatively low risk. 3. Achieved classification of two distinct subtypes of NAFLD, highlighting the necessity for personalized therapeutic strategies. 4. TNF, IL6, CCL5, and SPP1 were identified as potential therapeutic targets for NAFLD intervention.

  PublisherDOI

• Characterizing the expression profile of Dexras1 in human trabecular meshwork cells

  Biochemistry and Biophysics Reports · 2025-06-10

  articleOpen accessSenior authorCorresponding

  Corticosteroids are a mainstay therapy for the treatment of ocular and systemic inflammatory conditions but are associated with a significant risk of intraocular pressure elevation, or ocular hypertension. If intraocular pressure is inadequately controlled, steroid-induced glaucoma may develop, which can result in permanent vision loss and irreversible blindness. Pathological changes akin to fibrosis in the trabecular meshwork, the tissue responsible for intraocular pressure regulation, have been well described and contribute to the development of steroid-induced ocular hypertension and glaucoma. However, the molecular mechanisms driving these fibrosis-like changes in the trabecular meshwork following steroid treatment remain poorly understood. RASD1 is a gene coding for Dexras1, a small G protein of the Ras family discovered based on its marked induction by the synthetic glucocorticoid dexamethasone. Accumulating evidence points to the role of glucocorticoids in alterations of trabecular meshwork cell morphology, growth, and cell-extracellular matrix interactions. Therefore, we sought to confirm and further characterize how glucocorticoid-induced Dexras1 expression may contribute to glaucoma pathology in vitro . In this study, we found that dexamethasone significantly upregulated the expression of Dexras1 in trabecular meshwork cells within 30 min to 1 h post treatment. In addition, we discovered two phenotypes of Dexras1 induction independent of glucocorticoid responsiveness: younger and older donors show significant upregulation of Dexras1, whereas middle-aged donors experience little to no changes in Dexras1 expression after dexamethasone treatment. This age-dependent Dexras1 response may provide a novel explanation for the greater prevalence of steroid-induced glaucoma observed in older and younger populations as opposed to middle-aged populations. • Steroid glaucoma is related to pathologic changes in the trabecular meshwork. • Dexras1 is a protein induced in tissues in response to dexamethasone (dex). • We examined Dexras1 expression in nine human trabecular meshwork cell strains. • Dex results in time-dependent upregulation of Dexras1 in trabecular meshwork cells. • We theorize that Dexras1-induced adipogenesis contributes to steroid glaucoma.

  PublisherDOI

Recent grants

• NIH Grant R01GM069916

  NIH · $1.3M · 2009

• NIH Grant R01GM100909

  NIH · $1.5M · 2017

• Development of small-molecule Wnt mimetics for corneal epithelial cell regeneration

  NIH · $2.0M · 2018–2023

• NIH Grant R01GM081492

  NIH · $1.2M · 2012

• NIH Grant R01GM061739

  NIH · $1.0M · 2006

Frequent coauthors

• Robert Callender

  Albert Einstein College of Medicine

  36 shared

• Clémence Bonnet

  Centre de Recherche des Cordeliers

  35 shared

• Sophie X. Deng

  University of California, Los Angeles

  30 shared

• Ju Bao

  26 shared

• John W. Burgner

  22 shared

• Jufang Shan

  22 shared

• David Cowburn

  Albert Einstein College of Medicine

  21 shared

• Ho‐Jin Lee

  LeMoyne–Owen College

  20 shared

Labs

• Jie Zheng LabPI

Awards & honors

• Suzanne Eaton, Ph.D. Memorial Prize
• Taylor M. Brown Memorial Award
• Asrican Sophie & Jack Award