Overview
Our research program integrates cancer neuroscience, immunology, and cellular engineering to address fundamental challenges in treating glioblastoma and other brain tumors. We employ a multidisciplinary approach combining basic science, translational research, and clinical collaboration to develop next-generation immunotherapies.
Research Areas
Cancer Neuroscience
Brain tumors exist in a unique microenvironment shaped by neurons, glia, and specialized immune cells. We investigate how this neuro-immune crosstalk influences tumor growth, invasion, and treatment resistance. Our work explores:
- Mechanisms of neural-tumor interactions
- Role of neurotransmitters and neuropeptides in tumor progression
- Impact of neuroinflammation on tumor immunity
- Metabolic adaptations in the brain tumor microenvironment
Cancer Immunology
The immune landscape of glioblastoma is characterized by profound immunosuppression. We study the cellular and molecular mechanisms underlying immune dysfunction in brain tumors, including:
- Regulatory T cell (Treg) accumulation and function
- Myeloid-derived suppressor cells (MDSCs) and tumor-associated macrophages
- Checkpoint molecule expression and immune evasion
- Cytokine and chemokine networks in the tumor microenvironment
- Mechanisms of immunosuppression induced by metabolic dysregulation
CAR-T Cell Therapy
Chimeric antigen receptor (CAR) T cell therapy represents a promising approach for glioblastoma treatment. Our laboratory develops novel CAR-T cell engineering strategies to overcome obstacles specific to solid tumors:
- Target Antigen Discovery: Identifying and validating tumor-associated antigens including CD70, CXCR1/2, and emerging targets
- Enhanced Tumor Trafficking: Engineering CARs with chemokine receptors (e.g., CXCR1/2) to improve T cell migration into tumors
- Metabolic Optimization: Modifying CAR-T cells to thrive in the hostile tumor metabolic environment
- Checkpoint Modulation: Integrating checkpoint blockade (e.g., LAIR1) with CAR-T therapy
- Multi-targeting Strategies: Developing combination approaches to prevent antigen escape
Notable achievements include the development of CD70-targeted CAR-T cells and CXCR2-modified CAR-T cells that co-opt tumor-derived IL-8 for enhanced chemotaxis and anti-tumor efficacy.
Glioblastoma Research
Glioblastoma is the most aggressive primary brain tumor with a median survival of less than 15 months despite aggressive treatment. Our laboratory focuses on:
- Understanding mechanisms of treatment resistance to radiation and chemotherapy
- Identifying biomarkers for patient stratification and treatment response
- Developing combination therapeutic strategies
- Investigating the role of tumor heterogeneity in treatment failure
- Exploring the contribution of glioma stem cells to recurrence
Neuro-oncology Translational Research
We are committed to translating laboratory discoveries into clinical applications. Our translational efforts include:
- Preclinical validation of novel immunotherapies in patient-derived xenograft models
- Development of IND-enabling studies for CAR-T cell therapies
- Biomarker discovery for clinical trial design
- Collaboration with clinical neuro-oncology teams to inform research priorities
- Investigation of cerebrospinal fluid (CSF) diagnostics for disease monitoring
Key Publications
Our research has resulted in high-impact publications in leading journals including Nature Communications, Neuro-Oncology, Cancer Research, Pharmacological Research, and others. Selected highlights include:
- CXCR1/2-modified CAR T cells co-opt IL-8 for maximal antitumor efficacy (Nat Commun, 2019)
- CD70 as a novel target of CAR T-cell therapy for gliomas (Neuro-Oncology, 2018)
- Dysregulation of glutamate transport enhances Treg function promoting VEGF blockade resistance (Cancer Res, 2020)
- Novel immune checkpoint LAIR1 blockade for glioblastoma therapy (ongoing clinical development)
For a complete list, please visit our Publications page.
Funding & Collaborations
Our research is supported by the National Natural Science Foundation of China, Zhejiang Provincial Natural Science Foundation, and other funding agencies. We maintain active collaborations with leading institutions both domestically and internationally, fostering a rich environment for scientific exchange and innovation.
Research Opportunities
We offer opportunities for graduate students, postdoctoral fellows, and visiting scholars to engage in cutting-edge research at the intersection of neuroscience, immunology, and cancer therapy. If you are interested in joining our team, please visit our Contact page.