Philippe Gui
A5001552336- Click Chemistry and Applications
- Lung Cancer Treatments and Mutations
- Peptidase Inhibition and Analysis
- Nanoparticle-Based Drug Delivery
- Liver physiology and pathology
- Immune cells in cancer
- Protein Degradation and Inhibitors
- PI3K/AKT/mTOR signaling in cancer
- Cancer Genomics and Diagnostics
- RNA modifications and cancer
- Protease and Inhibitor Mechanisms
- Chemical Reactions and Isotopes
- Chronic Lymphocytic Leukemia Research
- Cancer Cells and Metastasis
- Single-cell and spatial transcriptomics
- Colorectal Cancer Treatments and Studies
- Cancer Mechanisms and Therapy
- Glutathione Transferases and Polymorphisms
- Hepatocellular Carcinoma Treatment and Prognosis
- Cancer-related Molecular Pathways
- Ferroptosis and cancer prognosis
- Cancer Research and Treatments
- Cancer therapeutics and mechanisms
- Extracellular vesicles in disease
- MicroRNA in disease regulation
University of California, San Francisco
2018-2024
UCSF Helen Diller Family Comprehensive Cancer Center
2018-2024
CollegeAmerica
2021
Institut de Pharmacologie et de Biologie Structurale
2014-2018
Centre National de la Recherche Scientifique
2014
Université de Toulouse
2014
Université Toulouse III - Paul Sabatier
2014
Inserm
2014
Institut des Maladies Métaboliques et Cardiovasculaires
2014
Lung cancer, the leading cause of cancer mortality, exhibits heterogeneity that enables adaptability, limits therapeutic success, and remains incompletely understood. Single-cell RNA sequencing (scRNA-seq) metastatic lung was performed using 49 clinical biopsies obtained from 30 patients before during targeted therapy. Over 20,000 tumor microenvironment (TME) single-cell profiles exposed a rich dynamic ecosystem. scRNA-seq cells illuminated targetable oncogenes beyond those detected...
Abstract In this study, the impact of apolipoprotein B mRNA-editing catalytic subunit-like (APOBEC) enzyme APOBEC3B (A3B) on epidermal growth factor receptor (EGFR)-driven lung cancer was assessed. A3B expression in EGFR mutant (EGFRmut) non-small-cell (NSCLC) mouse models constrained tumorigenesis, while tumors treated with EGFR-targeted therapy associated treatment resistance. Analyses human NSCLC showed upregulation and revealed therapy-induced activation nuclear kappa (NF-κB) as an...
Adipose tissue fibrosis development blocks adipocyte hypertrophy and favors ectopic lipid accumulation. Here, we show that adipose is associated with obesity insulin resistance in humans mice. Kinetic studies C3H mice fed a high-fat diet activation of macrophages progression along metabolic dysfunction death. attenuated by macrophage depletion. Impairment Toll-like receptor 4 signaling protects from obesity-induced fibrosis. The presence functional on hematopoietic cells necessary for the...
Although patients with advanced-stage non-small cell lung cancers (NSCLC) harboring MET exon 14 skipping mutations (METex14) often benefit from tyrosine kinase inhibitor (TKI) treatment, clinical is limited by primary and acquired drug resistance. The molecular basis for this resistance remains incompletely understood.Targeted sequencing analysis was performed on cell-free circulating tumor DNA obtained 289 METex14-mutated NSCLC.Prominent co-occurring RAS-MAPK pathway gene alterations (e.g.,...
Macrophage tissue infiltration can promote tumour development. Depending on the extracellular matrix architecture, macrophages adopt two migration modes: amoeboid (AM), common to all leukocytes; and mesenchymal (MM), restricted certain cells. Here, we investigated initiating mechanisms involved in macrophage MM. We show that a single is able use both modes. MM correlated with decreased Rho/Rho-associated protein kinase (ROCK) activity potentiated by ROCK inhibition, suggesting AM inhibition...
Abstract Macrophage recruitment is essential for tissue homeostasis but detrimental in most cancers. Tumor-associated macrophages (TAMs) play a key role cancer progression. Controlling their migration is, thus, potentially therapeutic. It assumed that use amoeboid motility vivo like other leukocytes. However, it has not yet been explored. We examined TAM using intravital microscopy mouse tumors and by monitoring ex infiltration human surgical samples. demonstrated TAMs perform...
Introductory paragraph The clinical success of targeted cancer therapy is limited by drug resistance that renders cancers lethal in patients 1-4 . Human tumours can evolve acquiring de novo genetic alterations and increased heterogeneity via mechanisms remain incompletely understood 1 Here, through parallel analysis human samples, tumour xenograft cell line models murine model systems, we uncover an unanticipated mechanism therapy-induced adaptation fuels the evolution resistance. Targeted...
Phosphatase and tensin homolog deleted on chromosome 10 (PTEN) is a tumor suppressor bi-functional lipid protein phosphatase. We report that the metabolic regulator pyruvate dehydrogenase kinase1 (PDHK1) synthetic-essential gene in PTEN-deficient cancer normal cells. The PTEN phosphatase dephosphorylates nuclear factor κB (NF-κB)-activating (NKAP) limits NFκB activation to suppress expression of PDHK1, NF-κB target gene. Loss upregulates PDHK1 induce aerobic glycolysis cellular dependence....
Abstract Genetic interactions impact both normal human physiology and diseases, such as cancer. Here, we study genetic through the lens of lung cancers driven by oncogenic forms epidermal growth factor receptor (EGFR), which others previously showed harbor a rich landscape co-alterations potential interactions. Among most common with EGFR are genomic amplifications cell cycle regulators CDK4 or CDK6 , have been implicated in inhibitor clinical resistance, although mechanism underlying this...
Lung cancer, the leading cause of cancer mortality, exhibits heterogeneity that enables adaptability, limits therapeutic success, and remains incompletely understood. Single-cell RNA sequencing (scRNAseq) metastatic lung was performed using 44 tumor biopsies obtained longitudinally from 27 patients before during targeted therapy. Over 20,000 microenvironment (TME) single-cell profiles exposed a rich dynamic ecosystem. scRNAseq cells illuminated targetable oncogenes beyond those detected...
Abstract Lung cancer is the leading cause of mortality, and despite improvements in treatment, tumors typically respond incompletely resume growth after acquisition drug resistance. Recent completion a neoadjuvant osimertinib Phase II trial treating patients with surgically resectable stage I-IIIA EGFR-mutated non-small cell lung (EGFRm NSCLC) (NCT03433469) (Blakely et. Al, JCO 2024) has highlighted importance further identifying non-genomic mechanisms persistence resistance to targeted...
Abstract Osimertinib sensitive and resistant NSCLC NCI-H1975 clones are used to model osimertinib acquired resistance in humanized non-humanized mice delineate potential mechanisms. No new EGFR mutations or loss of the T790M mutation found clones. Resistant tumors grown under continuous pressure both show aggressive tumor regrowth which is significantly less as compared with parental tumors. 3-phosphoinositide-dependent kinase 1 (PDK1) identified a driver resistance, its selective inhibition...
Abstract PURPOSE While patients with advanced-stage non-small cell lung cancers (NSCLCs) harboring MET exon 14 skipping mutations ( METex 14) often benefit from tyrosine kinase inhibitor (TKI) treatment, clinical is limited by primary and acquired drug resistance. The molecular basis for this resistance remains incompletely understood. METHODS Targeted sequencing analysis was performed on cell-free circulating tumor DNA obtained 289 14-mutated NSCLC. RESULTS Prominent co-occurring RAS-MAPK...
Abstract Osimertinib sensitive and resistant NSCLC NCI-H1975 clones were used to model osimertinib acquired resistance in humanized mice delineate potential mechanisms. No new EGFR mutations or loss of the T790M mutation found clones. Resistant tumors initially partially responsive osimertinib, then aggressive tumor regrowth occurred accompanied by an immunosuppressive microenvironment. 3-phosphoinositide-dependent kinase 1 (PDK1) was identified as a driver resistance, its selective...
<p>The MET F1200 residue is conserved across multiple tyrosine kinases</p>
<p>Summary of mutation clonality across patient cohorts</p>
<p>KRAS amplification and/or KRAS G12D mutation in METex14-mutated NSCLC with resistance to crizotinib</p>
<p>Demographics of the METex14-mutated and EGFR-mutated cohorts.</p>
<p>Genes included in NGS Panels</p>
<p>Flowchart describing sample filtering for predicted functional impact.</p>
<p>MET tyrosine kinase domain modeling location of the F1200 residue</p>
<p>Relative cell viability of Ba/F3 METex14-mutant expressing cells treated with trametinib monotherapy</p>