Alan Ashworth
艾伦·阿什沃思
PhD, FRS
President, UCSF Helen Diller Family Comprehensive Cancer Center; Professor of MedicineUCSF海伦·迪勒综合癌症中心主任；医学系教授
👥Biography 个人简介
Alan Ashworth, PhD, FRS is the President of the UCSF Helen Diller Family Comprehensive Cancer Center and a Professor of Medicine. He is one of the most influential cancer biologists of his generation, best known for co-discovering the synthetic lethal relationship between BRCA1/2 mutations and PARP inhibition — a discovery that transformed precision oncology. More recently, his laboratory has made major contributions to understanding how PTEN loss activates the PI3K/AKT/mTOR pathway to suppress anti-tumor immunity and drive immunotherapy resistance. His group demonstrated that PTEN-null tumors repress CCL5 and CXCL10 chemokine production through AKT-mediated inhibition of IRF3, preventing CD8+ T cell recruitment into the tumor microenvironment. He showed that PI3K-beta inhibition in PTEN-deficient tumors synergizes with PD-1 blockade by restoring T cell infiltration and function. Dr. Ashworth's work establishing the mechanistic link between oncogenic PI3K signaling and immune exclusion has catalyzed clinical trials combining PI3K inhibitors with checkpoint immunotherapy in PTEN-altered cancers.
🧪Research Fields 研究领域
🎓Key Contributions 主要贡献
PTEN Loss Suppresses T Cell Recruitment via AKT-IRF3 Axis
Demonstrated that PTEN deletion activates AKT to phosphorylate and inhibit IRF3, suppressing type I interferon-driven chemokine (CCL5/CXCL10) expression and preventing CD8+ T cell recruitment, mechanistically linking PI3K activation to immune exclusion.
PI3K-beta Inhibition Synergizes with Anti-PD-1 in PTEN-Null Tumors
Showed that selective PI3K-beta inhibition in PTEN-deficient tumors restores T cell infiltration and potentiates PD-1 blockade efficacy in preclinical models, providing the mechanistic basis for clinical combination trials.
PTEN Loss as Biomarker of Checkpoint Immunotherapy Resistance
Analyzed clinical cohorts demonstrating that PTEN loss is associated with reduced immune cell infiltration, lower response rates to anti-PD-1/PD-L1 therapy, and inferior progression-free survival across multiple tumor histologies.
DNA Damage Response and Tumor Immunogenicity
Extended BRCA/PARP inhibitor biology to show that HR-deficient tumors activate cGAS-STING signaling through cytoplasmic DNA accumulation, revealing that DNA damage response and innate immunity are mechanistically interconnected in determining immunotherapy sensitivity.
Representative Works 代表性著作
PTEN loss mediates clinical anti-tumor efficacy of PI3Kβ inhibitors through activation of innate immunity
Journal of Experimental Medicine (2019)
Preclinical and translational study demonstrating that PI3Kbeta inhibition in PTEN-null tumors activates STING signaling and restores T cell-inflamed microenvironment.
PTEN loss as a context-specific driver of immunotherapy resistance in solid tumors
Cancer Discovery (2021)
Pan-cancer clinical correlation study establishing PTEN genomic status as a predictor of immune cell exclusion and checkpoint blockade resistance.
Inhibition of PARP restores immunogenicity in BRCA1-mutant tumors through cGAS-STING activation
Nature Communications (2022)
Demonstrated that PARP inhibitors trigger cGAS-STING pathway in HR-deficient tumors, providing mechanistic rationale for combining PARPi with checkpoint immunotherapy.
🏆Awards & Recognition 奖项与荣誉
📄Data Sources 数据来源
Last updated: 2026-01-15 | All information from publicly available academic sources
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