B. G. Neel

Adeno-to-squamous transition drives resistance to KRAS inhibition in LKB1 mutant lung cancer

The paper identifies adeno-to-squamous transition (AST) as a mechanism of resistance to KRAS inhibitors in LKB1 mutant lung cancer and links KRT6A expression to poor patient outcomes.

Identification of a Hypoxia-induced Inflammatory Cell Death Pathway

The paper identifies a hypoxia-induced inflammatory cell death pathway involving PTP1B, RNF213, and CYLD/SPATA2, showing their role in tumor cell death and potential therapeutic targeting.

Endocytic vesicles act as vehicles for glucose uptake in response to growth factor stimulation

The paper shows that glucose uptake via GLUT1 co-endocytoses with PDGF receptor upon PDGF stimulation, delivering glucose to mitochondria for glycolysis.

Genome-wide CRISPR/Cas9 Screens Reveal Shared and Bespoke Mechanisms of Resistance to SHP2 inhibition

This study identifies genes conferring resistance to SHP2 inhibitors through CRISPR screens and shows their roles in reactivating ERK signaling in cancer cells.

Dual inhibition of SHP2 and autophagy suppresses NF1-associated Malignant Peripheral Nerve Sheath Tumors

This study shows that combining SHP2 and autophagy inhibition effectively suppresses NF1-associated MPNSTs in mouse models, suggesting a potential new treatment approach.

Combined Inhibition of SHP2 and CXCR1/2 Promotes Anti-Tumor T Cell Response in NSCLC

This study shows that combining SHP2 and CXCR1/2 inhibitors enhances anti-tumor T cell responses in NSCLC by reducing immunosuppressive gMDSCs and promoting effector T cells.

SHP2 Inhibition Abrogates Adaptive Resistance to KRASG12C-Inhibition and Remodels the Tumor Microenvironment of KRAS-Mutant Tumors

This study shows that combining SHP2 inhibitors with KRASG12C inhibitors enhances efficacy in PDAC and NSCLC by overcoming resistance and remodeling the tumor microenvironment.

Ontogeny and Vulnerabilities of Drug-Tolerant Persisters in HER2+ Breast Cancer

This study identifies drug-tolerant persisters (DTPs) in HER2+ breast cancer and reveals their origins and vulnerabilities to TKI resistance.

Moyamoya Disease-Associated RNF213 Alleles Encode Dominant Negative Alleles That Globally Impair Ubiquitylation

This study identifies MMD-associated RNF213 SNPs as dominant negative alleles that impair ubiquitylation, suggesting reduced E3-ligase activity as central to MMD pathogenesis.

Genetically Defined, Syngeneic Organoid Platform for Developing Combination Therapies for Ovarian Cancer

This paper develops a genetically defined, syngeneic organoid platform for ovarian cancer to evaluate combination therapies and finds genotype-specific responses to immunotherapy and chemotherapy.

Both Fallopian Tube and Ovarian Surface Epithelium Can Act as Cell-of-Origin for High Grade Serous Ovarian Carcinoma

This paper shows that both fallopian tube and ovarian surface epithelium can originate high grade serous ovarian carcinoma, with distinct biological properties and therapeutic responses.

Off-target inhibition by active site-targeting SHP2 inhibitors

The paper shows that some SHP2 inhibitors have off-target effects on PDGFRβ and SRC, suggesting caution in interpreting their specific biological roles.

SHP2 Is Required for BCR-ABL1-Induced Hematologic Neoplasms

This study shows SHP2 is essential for BCR-ABL1-induced hematologic cancers, affecting proliferation and signaling pathways in pre-B cells.

Assay to visualize specific protein oxidation reveals spatio-temporal regulation of SHP2

The paper visualizes SHP2 oxidation in cells using a combined PLA and chemical labeling assay, revealing PDGF-induced spatial and temporal regulation of SHP2 oxidation near endosomes.

Cellular Interplay and Cytokine Hierarchy Cause Pathological Cardiac Hypertrophy in RAF1-Mutant Noonan Syndrome

This study shows that RAF1 mutations in Noonan syndrome cause cardiac hypertrophy through cytokine signaling from endothelial cells, with TNF/IL6 as potential therapeutic targets.