A5015307563- Lung Cancer Treatments and Mutations
- Cancer Genomics and Diagnostics
- Gene expression and cancer classification
- Head and Neck Cancer Studies
- RNA Research and Splicing
- Cancer Diagnosis and Treatment
- Cancer-related gene regulation
- Sarcoma Diagnosis and Treatment
- PI3K/AKT/mTOR signaling in cancer
- Molecular Biology Techniques and Applications
- Virus-based gene therapy research
- Cancer-related molecular mechanisms research
- Parvovirus B19 Infection Studies
- Cutaneous lymphoproliferative disorders research
- Eosinophilic Disorders and Syndromes
- Immunodeficiency and Autoimmune Disorders
- Nonmelanoma Skin Cancer Studies
- Mosquito-borne diseases and control
- Peptidase Inhibition and Analysis
- Viral-associated cancers and disorders
- MicroRNA in disease regulation
- Inflammatory mediators and NSAID effects
- Genomics and Chromatin Dynamics
- Acne and Rosacea Treatments and Effects
- IL-33, ST2, and ILC Pathways
University of Pennsylvania
2021-2024
Government of the United States of America
2022
Federal Reserve
2022
Washington University in St. Louis
2017-2020
University of Pittsburgh
2013-2019
Eye and Ear Foundation
2019
University of Pittsburgh Medical Center
2019
Carnegie Mellon University
2013-2017
University of Utah
2010-2016
University of Michigan
2016
Genomic findings underscore the heterogeneity of head and neck squamous cell carcinoma (HNSCC). Identification mutations that predict therapeutic response would be a major advance. We determined mutationally altered, targetable mitogenic pathways in large HNSCC cohort. Analysis whole-exome sequencing data from 151 tumors revealed phosphoinositide 3-kinase (PI3K) pathway to most frequently mutated oncogenic (30.5%). PI3K pathway-mutated harbored significantly higher rate known cancer genes....
Abstract Nasopharyngeal carcinoma (NPC) is an aggressive head and neck cancer characterized by Epstein-Barr virus (EBV) infection dense lymphocyte infiltration. The scarcity of NPC genomic data hinders the understanding biology, disease progression rational therapy design. Here we performed whole-exome sequencing (WES) on 111 micro-dissected EBV-positive NPCs, with 15 cases subjected to further whole-genome (WGS), determine its mutational landscape. We identified enrichment for aberrations...
BACKGROUND. Recurrence and/or metastasis occurs in more than half of patients with head and neck squamous cell carcinoma (HNSCC), these events pose the greatest threats to long-term survival. We set out identify genetic alterations that underlie recurrent/metastatic HNSCC.
Skin is composed of diverse cell populations that cooperatively maintain homeostasis. Up-regulation the nuclear factor κB (NF-κB) pathway may lead to development chronic inflammatory disorders skin, but its role during early events remains unclear. Through analysis single-cell RNA sequencing data via iterative random forest leave one out prediction, an explainable artificial intelligence method, we identified immunoregulatory for a unique paired related homeobox-1 (Prx1) + fibroblast...
The significance of human papillomavirus (HPV) in nasopharyngeal carcinomas (NPCs) a low-incidence population remains unknown.Samples from 90 patients with NPC (years, 1957-2012) were analyzed for Epstein-Barr virus (EBV). Clinical data, EBV, HPV, and p16 status correlated overall survival (OS; 63 cases; years, 1981-2012).Of 9 HPV-positive cases, 3 extended extra-nasopharyngeal sites. Nasopharyngeal origin was confirmed 6 cases. had OS similar to EBV-positive (85 vs 141 months; p > .05)....
Aberrant activation of EGFR in human cancers promotes tumorigenesis through stimulation AKT signaling. Here, we determined that the discoidina neuropilin-like membrane protein DCBLD2 is upregulated clinical specimens glioblastomas and head neck (HNCs) required for EGFR-stimulated tumorigenesis. In multiple cancer cell lines, activated phosphorylation tyrosine 750 (Y750) DCBLD2, which located within a recently identified binding motif TNF receptor-associated factor 6 (TRAF6). Consequently,...
Chikungunya virus (CHIKV) is an arthritogenic alphavirus that acutely causes fever as well severe joint and muscle pain. Chronic musculoskeletal pain persists in a substantial fraction of patients for months to years after the initial infection, yet we still have poor understanding what promotes chronic disease. While replicating has not been detected joint-associated tissues with persistent arthritis nor various animal models at convalescent time points, viral RNA acute infection. To...
Abstract Background Patients with recurrent/metastatic head and neck squamous cell carcinoma (HNSCC) demonstrate aberrant activation of the phosphotidylinositol‐3‐kinase (PI3K)/Akt/mammalian target rapamycin (mTOR) pathway. We examined efficacy everolimus, an mTOR inhibitor, in patients recurrent or metastatic HNSCC. Methods This single‐arm phase II study enrolled biomarker‐unselected HNSCC who failed at least 1 prior therapy. Everolimus was administered until progressive disease...
Type I interferons (IFNs) are key mediators of the innate immune response. Although members this family cytokines signal through a single shared receptor, biochemical and functional variation exists in response to different IFN subtypes. While previous work has demonstrated that type IFNs essential control infection by chikungunya virus (CHIKV), globally emerging alphavirus, contributions individual subtypes remain undefined. To address question, we evaluated CHIKV pathogenesis mice lacking...
PIK3CA is the most commonly altered oncogene in head and neck squamous cell carcinoma (HNSCC). We evaluated impact of nonsteroidal anti-inflammatory drugs (NSAIDs) on survival a PIK3CA-characterized cohort 266 HNSCC patients explored mechanism relevant preclinical models including patient-derived xenografts. Among subjects with mutations or amplification, regular NSAID use (≥6 mo) conferred markedly prolonged disease-specific (DSS; hazard ratio 0.23, P = 0.0032, 95% CI 0.09–0.62) overall...
Sarcoidosis is a multiorgan granulomatous disease that lacks diagnostic biomarkers and targeted treatments. Using blood skin from patients with sarcoid non-sarcoid granulomas, we discovered granulomas different diseases exhibit unique immune cell recruitment molecular signatures. Sarcoid were specifically enriched for type 1 innate lymphoid cells (ILC1s) B exhibited programs associated formation of mature tertiary structures (TLSs), including increased CXCL12/CXCR4 signaling. Lung...
Previously, we reported modeling synovial sarcomas in mice by conditionally expressing the human t(X;18) translocation-derived SYT-SSX2 fusion protein Myf5-expressing myoblasts. Using a tamoxifen-inducible CreER system mice, show here that sporadic expression of across multiple tissue types leads to exclusive formation sarcoma-like tumors, whereas its widespread is lethal. Certain clinical and histologic features tumors this new model suggest additional nonmyoblast origin for sarcoma....
Abstract BYL719 is a PI3K inhibitor that has demonstrated efficacy in the treatment of head and neck squamous cell carcinoma. exerts its therapeutic effect by suppressing AKT other proliferative signaling mechanisms. Despite inhibition suppression, residual activity protein S6, core marker activation, been observed. HER3, either via dimerization or activation ligand neurgeulin (NRG), known to activate PI3K. Thus, we hypothesized co-targeting HER3 would lead greater suppression PI3K-AKT...
Synovial sarcoma (SS) is an aggressive soft-tissue that often discovered during adolescence and young adulthood. Despite the name, synovial does not typically arise from a synoviocyte but instead arises in close proximity to bones. Previous work demonstrated mice expressing characteristic SS18-SSX fusion oncogene myogenic factor 5–expressing (Myf5-expressing) cells develop fully penetrant sarcomagenesis, suggesting skeletal muscle progenitor cell origin. However, Myf5 restricted committed...
Sarcomatoid renal cell carcinoma (sRCC) is a highly aggressive form of dedifferentiated carcinoma. We report 62-year-old man who presented with respiratory symptoms and lung mass on chest computed tomography (CT). The patient underwent positron emission tomography/computed (PET/CT) 18F-fluorodeoxyglucose (18F-FDG) was found to have extensive metastatic disease. Based the history imaging findings, there were possible primary malignancies, including bronchogenic carcinoma, melanoma, or an...
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