A5021351784- Melanoma and MAPK Pathways
- Inflammatory Bowel Disease
- Microscopic Colitis
- Cytokine Signaling Pathways and Interactions
- HER2/EGFR in Cancer Research
- Lung Cancer Treatments and Mutations
- Monoclonal and Polyclonal Antibodies Research
- Gut microbiota and health
- Cancer Mechanisms and Therapy
- Helicobacter pylori-related gastroenterology studies
- Glycosylation and Glycoproteins Research
- Glioma Diagnosis and Treatment
- Colorectal Cancer Treatments and Studies
- IL-33, ST2, and ILC Pathways
- Protein Tyrosine Phosphatases
- Rheumatoid Arthritis Research and Therapies
- Cancer therapeutics and mechanisms
- Cancer-related molecular mechanisms research
- Galectins and Cancer Biology
- Gastrointestinal motility and disorders
- PI3K/AKT/mTOR signaling in cancer
- Sarcoidosis and Beryllium Toxicity Research
- Liver Diseases and Immunity
- Trace Elements in Health
- RNA Research and Splicing
Janssen (United States)
2016-2019
Johnson & Johnson (United States)
2018
University of Pennsylvania
2012-2014
Memorial Sloan Kettering Cancer Center
2012
Dana-Farber Cancer Institute
2012
Brigham and Women's Hospital
2012
Harvard University
2012
Broad Institute
2012
Abstract The clinical efficacy of epidermal growth factor receptor (EGFR) kinase inhibitors is limited by the development drug resistance. irreversible EGFR inhibitor WZ4002 effective against most common mechanism resistance mediated T790M mutation. Here, we show, in multiple complementary models, that to develops through aberrant activation extracellular signal-regulated (ERK) signaling caused either an amplification mitogen-activated protein 1 (MAPK1) or downregulation negative regulators...
The fecal microbiota is a rich source of biomarkers that have previously been shown to be predictive numerous disease states. Less well studied the effect immunomodulatory therapy on and its role in response therapy. This study explored associations between therapeutic Crohn's (CD) patients treated with ustekinumab (UST; Stelara) phase 2 CERTIFI study. Using stool samples collected over course 22 weeks, composition these subjects' bacterial communities was characterized by sequencing 16S...
Crohn's disease and ulcerative colitis are driven by both common distinct underlying mechanisms of pathobiology. Both diseases, exhibit heterogeneity underscored the variable clinical responses to therapeutic interventions. We aimed identify disease-driving pathways classify individuals into subpopulations that differ in their pathobiology response treatment. applied hierarchical clustering enrichment scores derived from gene set variation analysis signatures representative various...
Summary The molecular basis of sarcoidosis phenotype heterogeneity and its relationship to effective treatment have not been elucidated. Peripheral samples from subjects who participated in a Phase II study golimumab [anti-tumour necrosis factor (TNF)-α] ustekinumab [anti-interleukin (IL)−12p40] were used measure the whole blood transcriptome levels serum proteins. Differential gene protein expression analyses explore differences between phenotypes as defined by extent organ involvement....
Introduction: Heterogeneity in IBD patient populations is widely cited as the main barrier to efficient clinical trials and development of therapies with high efficacy. We others hypothesize that phenotypic heterogeneity a direct result molecular disease-driving pathways. present an approach not extensively explored for defining manner independent known biology. Methods: Whole genome transcriptomic data was generated colonic biopsies from 217 moderately severely active ulcerative colitis...
Introduction: CD and UC are thought to be driven by both common distinct pathobiology. Heterogeneity in diseases is underscored variability clinical responses therapeutic interventions. To explore this heterogeneity we aimed classify individuals into subgroups based on their pathobiology assess the relationship of these response anti-TNF. Methods: Colonic biopsies from healthy volunteers (HV), patients were analyzed performing hierarchical clustering enrichment scores (ES) calculated a...
<p>PDF file - 83K</p>
<p>PDF file - 1.3MB, Supplementary data on MAPK1 copy number and expression, combination treatment with WZ4002 PI3K inhibitors, impact of MEK1 K57N sensitivity, Mapk1 analyses NF1 dusp expression in drug sensitive resistant mouse tumors</p>
<p>PDF file - 1.3MB, Supplementary data on MAPK1 copy number and expression, combination treatment with WZ4002 PI3K inhibitors, impact of MEK1 K57N sensitivity, Mapk1 analyses NF1 dusp expression in drug sensitive resistant mouse tumors</p>
<p>PDF file - 83K</p>
<div>Abstract<p>The clinical efficacy of epidermal growth factor receptor (EGFR) kinase inhibitors is limited by the development drug resistance. The irreversible EGFR inhibitor WZ4002 effective against most common mechanism resistance mediated <i>EGFR</i> T790M mutation. Here, we show, in multiple complementary models, that to develops through aberrant activation extracellular signal-regulated (ERK) signaling caused either an amplification mitogen-activated protein 1...
<div>Abstract<p>The clinical efficacy of epidermal growth factor receptor (EGFR) kinase inhibitors is limited by the development drug resistance. The irreversible EGFR inhibitor WZ4002 effective against most common mechanism resistance mediated <i>EGFR</i> T790M mutation. Here, we show, in multiple complementary models, that to develops through aberrant activation extracellular signal-regulated (ERK) signaling caused either an amplification mitogen-activated protein 1...
Background: We investigated the relationship between fecal microbiome and clinical phenotypes in subjects with moderate to severe CD treated ustekinumab (UST) determine whether at baseline is predictive of disease severity therapeutic response assess changes microbiota due therapy. Methods: CERTIFI was a phase 2b multicenter, double-blind, placebo-controlled trial evaluate efficacy UST patients who had not responded anti-TNFα The 16S rRNA gene from stool samples collected roughly 350...
CD and UC are thought to be driven by both common distinct pathobiology. Heterogeneity in diseases is underscored variability clinical responses therapeutic interventions. To explore this heterogeneity we aimed classify individuals into subgroups based on their pathobiology assess the relationship of these response anti-TNF. Colonic biopsies from healthy volunteers (HV), patients were analyzed performing hierarchical clustering enrichment scores (ES) calculated a library gene signatures....
In this paper, we propose an analytic approach based on gene set variation analysis (GSVA) and network to compare different mouse inflammatory bowel disease (IBD) models assess their pertinence Crohn's ulcerative colitis.