J. A. Roth

NPRL2 gene therapy induces effective antitumor immunity in KRAS/STK11 mutant anti-PD1 resistant metastatic non-small cell lung cancer (NSCLC) in a humanized mouse model

This study shows NPRL2 gene therapy reduces lung metastases in KRAS/STK11 mutant NSCLC in humanized mice by enhancing immune cell infiltration and reducing T cell inhibitory signals.

Highly specific intracellular ubiquitination of a small molecule

The paper identifies a small molecule, BRD1732, that is ubiquitinated in cells, leading to proteasome inhibition through accumulation of ubiquitin chains.

Tumor-selective effects of active RAS inhibition in pancreatic ductal adenocarcinoma

This study evaluates the therapeutic potential of RMC-7977, a broad-spectrum RAS inhibitor, in pancreatic ductal adenocarcinoma models, showing strong anti-tumor effects with minimal impact on normal tissues.

Translation of non-canonical open reading frames as a cancer cell survival mechanism in childhood medulloblastoma

The paper investigates non-canonical ORF translation in medulloblastoma, identifying ASNSD1-uORF as critical for cell survival through interactions with the prefoldin-like chaperone complex.

Screening in serum-derived medium reveals differential response to compounds targeting metabolism

The paper screens compounds targeting metabolism in serum-derived medium to identify differential responses in cancer cells, aiming to improve drug response prediction.

Single-cell functional genomics of natural killer cell evasion in blood cancers

The paper uses single-cell and genome-scale functional genomics to study how blood cancer cells evade NK cells, identifying key genes and pathways involved in resistance and sensitivity.

Covalent Disruptor of YAP-TEAD Association Suppresses Defective Hippo Signaling

This paper develops a covalent inhibitor of the YAP-TEAD complex, demonstrating its ability to suppress Hippo signaling defects and inhibit cancer cell growth.

3-Phosphoinositide-dependent kinase 1 drives acquired resistance to osimertinib

This study identifies PDK1 as a driver of osimertinib resistance in NSCLC, showing its inhibition sensitizes resistant cells and correlates with disease progression.

A focal adhesion kinase-YAP signaling axis drives drug tolerant persister cells and residual disease in lung cancer

This study identifies a FAK-YAP signaling axis that drives drug-tolerant persister cells and residual disease in lung cancer, showing that inhibiting this axis improves tumor response to targeted therapies.

Salvage of Ribose from Uridine or RNA Supports Glycolysis when Glucose is Limiting

The paper identifies a pathway called uridinolysis that allows cells to use uridine and RNA-derived ribose to support glycolysis when glucose is limiting.

Massively parallel pooled screening reveals genomic determinants of nanoparticle-cell interactions

The paper uses a pooled screening approach to identify genomic factors influencing nanoparticle-cell interactions and validates biomarkers for nanoparticle uptake.

Non-canonical open reading frames encode functional proteins essential for cancer cell survival

The paper identifies non-canonical open reading frames (ORFs) that encode functional proteins essential for cancer cell survival, with one example, GREP1, showing preferential essentiality in breast cancer.

Probing the effect of glycosaminoglycan depletion on integrin interactions with collagen I fibrils in the native ECM environment.

This study investigates how glycosaminoglycan depletion affects integrin 2I domain interactions with collagen I fibrils and their mechanical properties in the ECM.

Multiplexed single-cell profiling of post-perturbation transcriptional responses to define cancer vulnerabilities and therapeutic mechanism of action

The paper introduces MIX-Seq, a method for multiplexed single-cell transcriptional profiling of cancer cell responses to perturbations, revealing drug mechanisms and predicting cell viability.

Pan-cancer single cell RNA-seq uncovers recurring programs of cellular heterogeneity

The paper uses single-cell RNA-seq to analyze cancer cell lines and identifies recurring expression programs of heterogeneity that mirror those in tumors, suggesting intrinsic plasticity contributes to intra-tumoral diversity.

Non-oncology drugs are a source of previously unappreciated anti-cancer activity

The paper identifies non-oncology drugs with anti-cancer activity across 578 cancer cell lines using PRISM, finding that many drugs selectively inhibit cancer cells based on molecular features.