David A. Largaespada

Biomarker-driven and gene-enhanced viral therapy for malignant peripheral nerve sheath tumor

This study develops a gene-enhanced HSV therapy for MPNST by exploiting PRC2 loss and tumor-regulated ICP34.5 expression to improve viral efficacy.

Medulloblastoma Forms Symbiotic Metabolic Partnerships with Macrophages to Establish Leptomeningeal Metastases

This study identifies metabolic partnerships between medulloblastoma and macrophages that drive leptomeningeal metastases and suggests targeting the CXCL12-SCARB1-cholesterol axis as a therapeutic strategy.

Integrated ex vivo screening and transcriptomic profiling to prioritize drug combinations for rare cancers

The paper develops EXACT, a framework combining ex vivo drug screening with transcriptomic analysis to identify effective drug combinations for rare cancers, finding a MEK and HDAC inhibitor combination shows enhanced activity.

Sleeping Beauty mutagenesis identifies BACH2 and other regulators of CD8+T cell exhaustion, persistence in vivo, and CAR-T function under tumor-associated chronic antigen stimulation

The paper uses Sleeping Beauty mutagenesis to identify BACH2 and other genes that enhance CD8+ T cell persistence and function under chronic antigen stimulation, improving engineered T cell therapies.

A modular, immunopeptidogenomic (iPepGen) analysis pipeline for discovery, verification, and prioritization of cancer peptide neoantigen candidates

The paper introduces a modular pipeline for neoantigen discovery, verification, and prioritization in cancer research using immunopeptidogenomic data.

The Cell Surface Proteome of Malignant Peripheral Nerve Sheath Tumors Reveals Therapeutic Targets

This study identifies cell surface proteome changes in MPNSTs due to PRC2 loss, revealing PTK7 as a promising therapeutic target using antibody-drug conjugates.

Pharmacogenomic synthetic lethal screens reveal hidden vulnerabilities and new therapeutic approaches for treatment of NF1-associated tumors

This study identifies 23 compounds that selectively kill NF1-deficient Schwann cells and shows their efficacy in vivo, with synergy when combined with Selumetinib.

Synergistic RAS-MAPK and AKT Activation in MYC-Driven Tumors via Adjacent PVT1 Rearrangements

This paper identifies how PVT1 rearrangements in MYC+ cancers generate oncogenic peptides that synergistically activate MYC, AKT, and RAS-MAPK pathways, enhancing tumor aggressiveness.

The assessment of therapeutic autophagy inhibition in NF1 mutated tumor cells

This study shows that autophagy inhibition enhances MEK inhibitor effectiveness in NF1-mutated tumor cells, both in vitro and in a clinical trial.

Cell type specific suppression of hyper-recombination by human RAD18 is linked to PCNA K164 ubiquitination

The paper shows that RAD18 inactivation in HCT116 cells increases recombination and reduces TLS activity, linked to PCNA K164 ubiquitination, but not SUMOylation.