About

Zhaoxia Qu is an Associate Professor of Immunology and Immune Therapeutics at the Keck School of Medicine of USC. Her research focuses on lung immunity, inflammation, and diseases, including lung cancer, which is the leading cause of cancer-related death in the U.S. and worldwide. Her lab utilizes mouse and human co-clinical models and state-of-the-art technologies to elucidate the molecular and cellular mechanisms underlying lung disease development, progression, and therapy resistance, with the aim of developing innovative therapies for lung cancer. Her work investigates the mechanisms of pulmonary immune regulation and its deregulation, particularly emphasizing innate immune components such as lung epithelial cells and macrophages. Her research also centers on key signaling pathways like NF-κB and STAT, which are master regulators of cell survival, proliferation, and immunity. Her contributions include advancing understanding of how immune signaling pathways influence lung tumorigenesis and immune responses, with a focus on translating these insights into prognostic, preventive, and therapeutic strategies.

Research topics

• Immunology
• Cancer research
• Biology
• Oncology
• Internal medicine
• Medicine

Selected publications

• AKT Signaling Differentially Regulates the Expression of Two Evolutionarily Conserved Wnt5a Isoforms in Lung Mesenchymal Cells

  Cells · 2026-05-04

  articleOpen access

  WNT5a is a lipid-modified glycoprotein member of the WNT family of signaling molecules. Two isoforms of WNT5a have been identified that are conserved across mice and humans. These isoforms display specific functions in regulating cancer cell activities. While WNT5a is, indeed, essential for normal lung development and homeostasis, and is dysregulated in multiple lung diseases, little to no information is available regarding the expression or potential function of WNT5a isoforms in normal or diseased lungs. Such information has the potential to help to elucidate the more precise and nuanced functions of WNT5a in various pulmonary conditions. In this study, we characterized the expression of individual Wnt5a isoforms during mouse lung development and compared their expression across major alveolar cell populations. We further investigated the molecular basis of the signaling mechanisms that regulate Wnt5a isoform expression in fibroblasts, the major lung cell type with high-level Wnt5a expression. We present data that reveal a role for the AKT pathway in differentially regulating the expression of Wnt5a isoforms, a novel finding. Furthermore, we demonstrate that Wnt5a isoforms are dysregulated in bleomycin-induced fibrosis and Pseudomonas aeruginosa (PA)-induced acute lung injury and exhibit distinct impacts in Wnt5a isoform expression in response to lung injury.

  PublisherDOI

• Specific inhibitor to KRAS^G12C induces tumor-specific immunity and synergizes with oncolytic virus for enhanced cancer immunotherapy

  Journal for ImmunoTherapy of Cancer · 2025-07-01 · 4 citations

  articleOpen access

  Background Oncolytic virus (OV)-mediated immunotherapy has been shown limited efficacy. Small molecule inhibitors specific to the KRAS G12C driver oncoprotein have recently been developed for cancer treatment. The combination of a potent OV with a KRAS G12C inhibitor could be a potent combination strategy for treating KRAS G12C cancer. Methods We explored combination therapies using KRAS G12C inhibitor and OV in cancer cells in vitro and in two KRAS G12C cancer models. We employed flow cytometry to evaluate the immune cell profiles, including dendritic cells, macrophages, myeloid-derived suppressor cells, natural killer (NK), subsets of CD4 + and CD8 + T cells, and exhaustion markers (CTLA-4, PD-1, TIM-3), activation markers (granzyme B, IFN-γ and 4-1BB) as well as enzyme-linked immunospot assay to identify tumor-antigen specific T cells. The importance of CD4 + , CD8 + T and NK cells in the therapeutic effects was evaluated by antibody-mediated depletion in vivo. Results We confirmed that three inhibitors for KRAS G12C , AMG510 (sotorasib), MRTX849 (adagrasib) and MRTX1257, all displayed potent cytotoxicity to cancer cells harboring KRAS G12C , but not to cancer cells without this specific KRAS mutation in vitro. All three inhibitors exhibited potent antitumor activity in KRAS G12C Lewis lung cancer, but not in MC38 colon cancer with wild-type KRAS. In two KRAS G12C tumor models, either an IL-36γ-armed OV or orally delivered MRTX1257 inhibited tumor growth, but the combination worked much more efficiently, and efficacy was further improved with PD-1 blockade although with no statistical difference in survival, leading to complete tumor remission in a large fraction of the mice. Mechanistic studies revealed that MRTX1257, and other KRAS G12C inhibitors as well, are potent inducers of antitumor immunity by themselves, and that it worked with OV to elicit potent innate and adaptive tumor-specific immunity. The combination therapeutic efficacy depended largely on increased tumor-specific CD8 + cytotoxic T cells, and to a smaller degree, on CD4 + T and NK cells. Conclusions Small molecule inhibitors of KRAS G12C are novel inducers of tumor-specific immunity, and a unique triple combination regimen is highly efficacious through elicited potent antitumor immunity for KRAS G12C cancers.

  PublisherOA PDFDOI

• Myeloid PDLIM2 repression as a common mechanism of infection susceptibility in lung diseases

  Frontiers in Immunology · 2025-11-19 · 3 citations

  articleOpen accessSenior authorCorresponding

  Introduction The PDZ-LIM domain-containing protein PDLIM2 serves as a unique tumor suppressor and immune modulator. Its repression in either lung epithelial or myeloid cells has been shown to promote lung cancer and therapy resistance. However, whether PDLIM2 plays a broader role in other lung diseases remains unclear. Methods Gene expression data on human samples were exploited to investigate if PDLIM2 is repressed in the lung of patients with chronic obstructive pulmonary disease (COPD) or interstitial lung disease (ILD/idiopathic pulmonary fibrosis (IPF). PDLIM2 conditional knockout (KO) mice and wild type (WT) control mice were intratracheally instilled with the bacterial endotoxin lipopolysaccharide (LPS) to induce acute lung injury (ALI), a murine model of human acute respiratory distress syndrome (ARDS) that can also provide mechanistic insights into COPD, pulmonary fibrosis (PF) and infectious disease. Kaplan-Meier estimator was used to determine animal survival rate, and histological analysis and single-cell RNA sequencing (scRNA-seq) of mouse lung tissues were performed to systematically define the roles of PDLIM2 at the population and single-cell level. Ex vivo phagocytosis and neutrophil extracellular trap (NET) formation assays were also performed to validate the scRNA-seq analysis. Results PDLIM2 was repressed in the lungs of COPD and ILD/IPF patients, and this repression was associated with disease severity. Selective deletion of PDLIM2 in myeloid cells rendered mice more vulnerable to lung injury and mortality by LPS intratracheal instillation. The increased susceptibility was linked to exacerbated pro-inflammation signaling and diminished anti-inflammation signaling in the lung, and particularly, in lung macrophages and neutrophils. Conclusions PDLIM2 plays an indispensable role in preventing ALI/ARDS and death, and its repression is associated with COPD and ILD progression. These data suggest that PDLIM2 repression, especially in lung myeloid cells, is a common mechanism driving COPD, ILD/IPF, and lung cancer and increasing patients’ susceptibility to infection.

  PublisherOA PDFDOI

• PDLIM2 in Lung Adenocarcinoma Metastasis

  bioRxiv (Cold Spring Harbor Laboratory) · 2025-12-07

  articleOpen access

  Abstract Human and mouse studies have established the unique PDZ-LIM domain-containing protein PDLIM2 as a common tumor suppressor that is especially vital for suppressing the tumorigenesis and therapeutic resistance of lung cancer, the leading cause of cancer-related deaths among both men and women. However, the role of PDLIM2 in tumor metastasis, the predominant cause of cancer morbidity and mortality, is yet to be determined. Here, we report that PDLIM2 repression was positively associated with the metastasis of human lung adenocarcinoma, the major type of non-small cell lung cancer that accounts for more than 40% of all cases of human lung cancer. Interestingly, PDLIM2 repression was also correlated with oncogenic KRAS and/or TP53 mutations, two common drivers of human lung adenocarcinoma that often co-occur. In mice, in comparison to concurrently inducing mutant KRAS expression and TP53 deletion, additional co-ablation of PDLIM2 significantly increased the number and size of lung adenocarcinomas in the lung, and more importantly, the distant metastasis of lung tumor cells. The increased metastasis was accompanied by decreased anti-tumor immunity and increased pro-tumor inflammation. These data demonstrate the role of PDLIM2 in suppressing lung adenocarcinoma metastasis, thereby improving our understanding of this crucial tumor suppressor and lung cancer. They also provide a useful model for studying metastasis and testing new lung cancer treatments in vivo .

  PublisherDOI

• PDLIM2 Repression: A Common Mechanism in Viral Lung Infection

  bioRxiv (Cold Spring Harbor Laboratory) · 2025-09-15 · 3 citations

  preprintOpen accessSenior authorCorresponding

  Background: PDLIM2, a PDZ-LIM domain-containing protein expressed highest in the lung and immune cells, serves as a unique tumor suppressor and immune modulator, mainly by turning off the activation of the master transcription factors NF-κB and STAT3. While its role in cancer is established, the involvement of PDLIM2 in viral infection remains unclear. Results: Here, we analyzed public gene expression data of blood leukocytes, bronchoalveolar lavage cells, and lung tissues from uninfected healthy humans and those infected with the respiratory virus SARS-CoV-2 or influenza. We found that PDLIM2 expression was repressed by viral infection, and notably, this repression correlated with the severity of infectious diseases. Consistently, the expression level of PDLIM2 was negatively associated with NF-κB and STAT3 activity across a diverse range of cell types, such as macrophages, monocytes, neutrophils, T cells, alveolar type 1 and 2 epithelial cells, airway epithelial cells, and fibroblasts. Accordingly, cells with low PDLIM2 expression exhibited aberrant activation of signaling pathways essential for cellular functions and immune responses. Conclusions: These findings highlight PDLIM2 repression as a common mechanism underlying human viral infectious diseases and suggest PDLIM2 as a potential biomarker and therapeutic target for disease prognosis, prevention, and treatment.

  PublisherOA PDFDOI

• SRC at the crossroads of KRAS inhibitor resistance: Mechanisms and therapeutic opportunities

  Cancer Letters · 2025-12-02 · 1 citations

  article
  PublisherDOI

• NanoPDLIM2-Based Combination Therapy for Lung Cancer Treatment in Mouse Preclinical Studies

  BIO-PROTOCOL · 2025-01-01 · 5 citations

  articleOpen accessSenior author

  This protocol describes the preparation, administration, and analysis of a nanoparticle-based therapeutic strategy (nanoPDLIM2) in combination with PD-1 immune checkpoint blockade immunotherapy and chemotherapy for the treatment of lung cancer in mouse preclinical studies. NanoPDLIM2 uses a polyethyleneimine (PEI)-based delivery system that encapsulates PDLIM2 expression plasmids for reconstituting PDLIM2 that is repressed in tumors. This approach induces tumor immunogenicity, suppresses drug resistance, and improves treatment efficacy when used in combination with carboplatin, paclitaxel, and anti-PD-1 antibodies. The protocol describes steps for mouse lung tumor induction, nanoPDLIM2 and other therapeutic reagents' preparation and administration, and subsequent analysis of tumor burden, immune response, and toxicity, providing a reproducible approach for investigators. Key features • Comprehensive workflow for preparation and delivery of nanoPDLIM2. • Combination of nanoPDLIM2 with PD-1 blockade and chemotherapeutics for superior efficacy in lung cancer treatment. • Detailed protocols for therapeutic reagents preparation, administration, tumor examination, immune analysis, health monitoring, and toxicity evaluation in a preclinical lung cancer model.

  PublisherDOI

• The Study of Public Health Policies for Alzheimer’s Disease Based on the Pathogenesis

  MedScien · 2024-12-31

  articleOpen access1st authorCorresponding

  In the current social context, the increasing aging population has led to a rising incidence of Alzheimer’s disease (AD). Today’s research primarily focuses on the development of new drugs for AD, exploration of its causes, and the formulation of reasonable policies for AD patients. As of now, there is still no curative drug available for AD. This article mainly analyzes the pathogenesis of AD, discussing its causes, symptoms, diagnostic methods, corresponding public strategies, measures, and care aspects, providing insights for the development of public health policies related to AD. Through this article, people can gain a better understanding of the mechanisms and pathology of AD, as well as the methods and policies for addressing it, while also recognizing the importance of improving public health policies for AD. It offers a general research direction for future studies, particularly concerning unresolved issues related to AD medications. It is hoped that future research will make further progress in developing new drugs specifically for AD.

  PublisherOA PDFDOI

• Reviewer #2 (Public Review): Improving PD-1 blockade plus chemotherapy for complete remission of lung cancer by nanoPDLIM2

  2024-02-13

  peer-reviewOpen accessSenior author

  Immune checkpoint inhibitors (ICIs) and their combination with other therapies such as chemotherapy, fail in most cancer patients. We previously identified the PDZ-LIM domain-containing protein 2 (PDLIM2) as a bona fide tumor suppressor that is repressed in lung cancer to drive cancer and its chemo and immunotherapy resistance, suggesting a new target for lung cancer therapy improvement.Human clinical samples and data were used to investigate PDLIM2 genetic and epigenetic changes in lung cancer. Using an endogenous mouse lung cancer model faithfully recapitulating refractory human lung cancer and a clinically feasible nano-delivery system, we investigated the therapeutic efficacy, action mechanism, and safety of systemically administrated PDLIM2 expression plasmids encapsulated in nanoparticles (nanoPDLIM2) and its combination with PD-1 antibody and chemotherapeutic drugs.PDLIM2 repression in human lung cancer involves both genetic deletion and epigenetic alteration. NanoPDLIM2 showed low toxicity, high tumor specificity, antitumor activity, and greatly improved the efficacy of anti-PD-1 and chemotherapeutic drugs, with complete tumor remission in most mice and substantial tumor reduction in the remaining mice by their triple combination. Mechanistically, nanoPDLIM2 increased major histocompatibility complex class I (MHC-I) expression, suppressed multi-drug resistance 1 (MDR1) induction and survival genes and other tumor-related genes expression in tumor cells, and enhanced lymphocyte tumor infiltration, turning the cold tumors hot and sensitive to ICIs and rendering them vulnerable to chemotherapeutic drugs and activated tumor-infiltrating lymphocytes (TILs) including those unleashed by ICIs.These studies established a clinically applicable PDLIM2-based combination therapy with great efficacy for lung cancer and possibly other cold cancers.

  PublisherDOI

• Author Response: Improving PD-1 blockade plus chemotherapy for complete remission of lung cancer by nanoPDLIM2

  2024-02-13

  peer-reviewOpen accessSenior author

  Immune checkpoint inhibitors (ICIs) and their combination with other therapies such as chemotherapy, fail in most cancer patients. We previously identified the PDZ-LIM domain-containing protein 2 (PDLIM2) as a bona fide tumor suppressor that is repressed in lung cancer to drive cancer and its chemo and immunotherapy resistance, suggesting a new target for lung cancer therapy improvement.Human clinical samples and data were used to investigate PDLIM2 genetic and epigenetic changes in lung cancer. Using an endogenous mouse lung cancer model faithfully recapitulating refractory human lung cancer and a clinically feasible nano-delivery system, we investigated the therapeutic efficacy, action mechanism, and safety of systemically administrated PDLIM2 expression plasmids encapsulated in nanoparticles (nanoPDLIM2) and its combination with PD-1 antibody and chemotherapeutic drugs.PDLIM2 repression in human lung cancer involves both genetic deletion and epigenetic alteration. NanoPDLIM2 showed low toxicity, high tumor specificity, antitumor activity, and greatly improved the efficacy of anti-PD-1 and chemotherapeutic drugs, with complete tumor remission in most mice and substantial tumor reduction in the remaining mice by their triple combination. Mechanistically, nanoPDLIM2 increased major histocompatibility complex class I (MHC-I) expression, suppressed multi-drug resistance 1 (MDR1) induction and survival genes and other tumor-related genes expression in tumor cells, and enhanced lymphocyte tumor infiltration, turning the cold tumors hot and sensitive to ICIs and rendering them vulnerable to chemotherapeutic drugs and activated tumor-infiltrating lymphocytes (TILs) including those unleashed by ICIs.These studies established a clinically applicable PDLIM2-based combination therapy with great efficacy for lung cancer and possibly other cold cancers.

  PublisherDOI

Recent grants

• Mechanistic difference of NF-kappaB in lung physiology and tumorigenesis

  NIH · $1.5M · 2022–2027

• NIH Grant R21CA189703

  NIH · $368k · 2018

Frequent coauthors

• Gutian Xiao

  University of Southern California

  183 shared

• Yadong Xiao

  University of Pittsburgh

  96 shared

• Steven D. Shapiro

  University of Southern California

  93 shared

• Fan Sun

  UPMC Hillman Cancer Center

  84 shared

• Pengrong Yan

  Memorial Sloan Kettering Cancer Center

  70 shared

• Liwen Li

  Tulane University

  50 shared

• Hongqiao Zhang

  Hastings Center

  49 shared

• Jingjiao Zhou

  39 shared