A5025478813- Pancreatic and Hepatic Oncology Research
- Advanced Breast Cancer Therapies
- Colorectal Cancer Treatments and Studies
- Protein Kinase Regulation and GTPase Signaling
- Melanoma and MAPK Pathways
- Cancer Genomics and Diagnostics
- Monoclonal and Polyclonal Antibodies Research
- HER2/EGFR in Cancer Research
- Advanced Biosensing Techniques and Applications
- Neuroendocrine Tumor Research Advances
- Lung Cancer Treatments and Mutations
- Bioinformatics and Genomic Networks
- PI3K/AKT/mTOR signaling in cancer
- Advanced Proteomics Techniques and Applications
- Cancer, Hypoxia, and Metabolism
- Gene Regulatory Network Analysis
- Cancer Mechanisms and Therapy
- Molecular Biology Techniques and Applications
- Cancer Research and Treatments
- Gene expression and cancer classification
- Computational Drug Discovery Methods
- Cancer Cells and Metastasis
- DNA Repair Mechanisms
- Microbial Metabolic Engineering and Bioproduction
- Click Chemistry and Applications
George Mason University
2016-2025
Azienda Ospedaliera di Perugia
2011-2015
University of Brescia
2014
Despite decades of research, efforts to directly target KRAS have been challenging. MRTX849 was identified as a potent, selective, and covalent KRASG12C inhibitor that exhibits favorable drug-like properties, selectively modifies mutant cysteine 12 in GDP-bound KRASG12C, inhibits KRAS-dependent signaling. demonstrated pronounced tumor regression 17 26 (65%) KRASG12C-positive cell line- patient-derived xenograft models from multiple types, objective responses observed patients with lung colon...
Mutational loss of CDKN2A (encoding p16INK4A) tumor-suppressor function is a key genetic step that complements activation KRAS in promoting the development and malignant growth pancreatic ductal adenocarcinoma (PDAC). However, pharmacologic restoration p16INK4A with inhibitors CDK4 CDK6 (CDK4/6) has shown limited clinical efficacy PDAC. Here, we found concurrent treatment both CDK4/6 inhibitor (CDK4/6i) an ERK-MAPK (ERKi) synergistically suppresses PDAC cell lines organoids by cooperatively...
To delineate the mechanisms by which ERK1 and ERK2 mitogen-activated protein kinases support mutant KRAS–driven cancer growth, we determined ERK-dependent phosphoproteome in KRAS-mutant pancreatic cancer. We that share near-identical signaling transforming outputs KRAS-regulated is driven nearly completely ERK. identified 4666 phosphosites on 2123 proteins, of 79 66%, respectively, were not previously associated with ERK, substantially expanding depth breadth phosphorylation events revealing...
We present a deep proteogenomic profiling study of 87 lung adenocarcinoma (LUAD) tumors from the United States, integrating whole-genome sequencing, transcriptome proteomics and phosphoproteomics by mass spectrometry, reverse-phase protein arrays. identify three subtypes somatic genome signature analysis, including transition-high subtype enriched with never smokers, transversion-high current structurally altered former TP53 alterations, genome-wide structural alterations. show that...
Endocrine therapy (ET) in combination with CDK4/6 inhibition is routinely used as first-line treatment for HR+/HER2- metastatic breast cancer (MBC) patients. However, 30-40% of patients quickly develop disease progression. In this open-label multicenter clinical trial, we utilized a hypothesis-driven protein/phosphoprotein-based approach to identify predictive markers response ET plus pre-treatment tissue biopsies. Pathway-centered signaling profiles were generated from microdissected tumor...
Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive disease with limited and, very often, ineffective medical and surgical therapeutic options. The treatment of patients advanced unresectable PDAC restricted to systemic chemotherapy, intervention which most eventually develop resistance. Recently, nab-paclitaxel (n-PTX) has been added the arsenal first-line therapies, combination gemcitabine n-PTX modestly prolonged median overall survival. However, almost invariably succumb...
Colorectal cancer (CRC) represents the fourth leading cause of cancer-related deaths. The heterogeneity CRC identity limits usage cell lines to study this type tumor because limited representation multiple features original malignancy. Patient-derived colon organoids (PDCOs) are a promising 3D-cell model for personalized medicine, although approach still lacks detailed characterization regarding molecular stability during culturing conditions. Correlation analysis that considers genomic,...
Abstract We performed a deep proteogenomic analysis of bulk tumor and laser microdissection enriched cell populations from high-grade serous ovarian cancer (HGSOC) tissue specimens spanning broad spectrum purity. identified patients with longer progression-free survival had increased immune-related signatures validated proteins correlating tumor-infiltrating lymphocytes in 65 tumors an independent cohort HGSOC patients, as well overall additional 126 patient cohort. that homologous...
Abstract Pancreatic ductal adenocarcinoma (PDAC) is characterized by KRAS- and autophagy-dependent growth. Inhibition of the KRAS-RAF-MEK-ERK pathway enhances autophagic flux dependency, concurrent treatment with nonspecific autophagy inhibitor chloroquine (CQ) ERK-MAPK inhibitors can synergistically block PDAC However, CQ limited in terms specificity potency. To find alternative anti-autophagy strategies, here we performed a CRISPR-Cas9 loss-of-function screen cell lines that identified...
The aim of this study was to evaluate whether upfront cellular enrichment via laser capture microdissection (LCM) is necessary for accurately quantifying predictive biomarkers in nonsmall cell lung cancer tumors.
Oncogenic KRAS drives cancer growth by activating diverse signaling networks, not all of which have been fully delineated. We set out to establish a system-wide profile the KRAS-regulated kinase network (kinome) in KRAS-mutant pancreatic ductal adenocarcinoma (PDAC). knocked down expression panel six cell lines and then applied multiplexed inhibitor bead/MS monitor changes activity and/or expression. hypothesized that depletion would result downregulation kinases required for KRAS-mediated...
// Elisa Baldelli 1,2 , Guido Bellezza 3 Eric B. Haura 4 Lucio Crinó 2 W. Douglas Cress Jianghong Deng 1 Vienna Ludovini Angelo Sidoni Matthew Schabath Francesco Puma 5 Jacopo Vannucci Annamaria Siggillino Lance A. Liotta Emanuel F. Petricoin III and Mariaelena Pierobon Center for Applied Proteomics Molecular Medicine, George Mason University, Manassas, VA, USA Medical Oncology Division, S. Maria della Misericordia Hospital, Perugia, Italy Department of Experimental Section Anatomic...
Epithelial ovarian carcinoma (EOC) is a deadly disease, with 5-year survival of 30%. The aim the study was to perform broad-scale protein signaling activation mapping evaluate if EOC can be redefined based on activated network architecture rather than histology. Tumor cells were isolated using laser capture microdissection (LCM) from 72 EOCs. Tumors classified as serous (n = 38), endometrioid 13), mixed 8), clear cell (CCC; n 7), and others 6). LCM tumor lysed subjected reverse-phase...
Abstract The cross‐talk between tumor epithelium and surrounding stromal/immune microenvironment is essential to sustain growth progression provides new opportunities for the development of targeted treatments focused on disrupting ecology. Identification novel approaches study these interactions primary importance. Using laser capture microdissection (LCM) coupled with reverse phase protein microarray (RPPA) based signaling activation mapping we explored molecular interconnection stromal in...
Despite multiple possible oncogenic mutations in the proto-oncogene KRAS , unique subsets of these are detected different cancer types. As occur early, if not being initiating event, mutational biases ostensibly a product how normal cells respond to encoded oncoprotein. Oncogenic can impact only level active oncoprotein, but also engagement with proteins. To attempt separate two effects, we generated four novel Cre-inducible (LSL) Kras alleles mice biochemically distinct G12D or Q61R and by...
The study of cancer therapy is a key issue in the field oncology research and development target therapies one main problems currently under investigation. This particularly relevant different types tumor where traditional chemotherapy approaches often fail, such as lung cancer. We started from general definition robustness introduced by Kitano applied it to analysis dynamical biochemical networks, proposing new algorithm based on moment independent input/output uncertainty. framework...
Abstract Reversible protein phosphorylation represents a key mechanism by which signals are transduced in eukaryotic cells. Dysregulated is also hallmark of carcinogenesis and drug targets the precision medicine space. Thus, methods that preserve phosphoprotein integrity context clinical tissue analyses crucially important cancer research. Here we investigated impact UV laser microdissection (UV LMD) IR capture (IR LCM) on abundance signaling assessed reverse-phase microarray (RPPA). Tumor...