A5019258496- PI3K/AKT/mTOR signaling in cancer
- Lung Cancer Treatments and Mutations
- Cancer-related molecular mechanisms research
- Salivary Gland Disorders and Functions
- RNA modifications and cancer
- Immune Response and Inflammation
- Oral Health Pathology and Treatment
- Oral microbiology and periodontitis research
- Immunotherapy and Immune Responses
- Cancer-related Molecular Pathways
- Bone health and treatments
- Hearing, Cochlea, Tinnitus, Genetics
- Viral-associated cancers and disorders
- Single-cell and spatial transcriptomics
- Virus-based gene therapy research
- Metabolism, Diabetes, and Cancer
- Cardiovascular and exercise physiology
- Cancer-related gene regulation
- Bone Tumor Diagnosis and Treatments
- Cancer, Lipids, and Metabolism
- Infectious Diseases and Mycology
- Peptidase Inhibition and Analysis
- Mesenchymal stem cell research
- Cancer Diagnosis and Treatment
- Histiocytic Disorders and Treatments
National Institute on Deafness and Other Communication Disorders
2018-2025
National Institutes of Health
2014-2024
National Institute of Dental and Craniofacial Research
2015-2024
University of Plymouth
2024
Caris Life Sciences (United States)
2021-2024
Weatherford College
2023
Centro Oftalmológico Moreiras
2022
Institute of Ophthalmology
2022
Rutgers, The State University of New Jersey
2018-2020
Rutgers Sexual and Reproductive Health and Rights
2019
Breast cancers often progress from a hormone-dependent, nonmetastatic, antiestrogen-sensitive phenotype to hormone-independent, antiestrogen- and chemotherapy-resistant with highly invasive metastatic growth properties. This progression is usually accompanied by altered function of the estrogen receptor (ER) or outgrowth ER-negative cancer cells. To understand molecular mechanisms responsible for breast cancers, activities transcription factor NF-kappaB (which modulates expression genes...
The phosphatidylinositol 3-kinase (PI3K)/Akt pathway elicits a survival signal against multiple apoptotic insults. In addition, phase II enzymes such as heme oxygenase-1 (HO-1) protect cells diverse toxins and oxidative stress. this work, we describe link between these defense systems at the level of transcriptional regulation antioxidant enzyme HO-1. herb-derived phenol carnosol induced HO-1 expression both mRNA protein levels. Luciferase reporter assays indicated that targeted mouse ho1...
Vascular endothelial growth factor (VEGF) is a potent mitogen and permeability for cells that plays central role in angiogenesis, vascular maintenance, inflammation, cancer. VEGF also mediates the homeostatic adaptation to hypoxic conditions by promoting an increase density compensate decreased oxygenation. This process triggered oxygen-sensitive transcription factor, hypoxia-inducible factor-1 (HIF1α), which becomes active tissues, leading synthesis secretion of VEGF. The HIF1α other...
Periodontitis is one of the most common human inflammatory diseases, yet mechanisms that drive immunopathology and could be therapeutically targeted are not well defined. Here, we demonstrate an expansion resident memory T helper 17 (TH17) cells in periodontitis. Phenocopying humans, TH17 expanded murine experimental periodontitis through local proliferation. Unlike homeostatic oral cells, which accumulate a commensal-independent interleukin-6 (IL-6)-dependent manner,...
// Daniel Martin 1 , C. Abba 2 Alfredo A. Molinolo Lynn Vitale-Cross Zhiyong Wang Moraima Zaida Naomi Delic 4, 5 Yardena Samuels 3 J. Guy Lyons Silvio Gutkind Oral and Pharyngeal Cancer Branch, National Institutes of Health, Bethesda, USA CINIBA, Facultad de Ciencias Médicas, Universidad Nacional La Plata, Argentina Department Molecular Cell Biology, The Weizmann Institute Science, Rehovot, Israel 4 Dermatology, University Sydney, Camperdown, Australia Services, Royal Prince Alfred...
Human monogenic disorders have revealed the critical contribution of type 17 responses in mucosal fungal surveillance. We unexpectedly found that certain settings, enhanced 1 immunity rather than defective can promote infection susceptibility. Notably, mice and humans with
Tissue-specific cues are critical for homeostasis at mucosal barriers. Here, we report that the clotting factor fibrin is a regulator of neutrophil function oral barrier. We demonstrate commensal microbiota trigger extravascular deposition in mucosa. Fibrin engages neutrophils through α
Aerobic cells adjust the expression of antioxidant enzymes to maintain reactive oxygen species within tolerable levels. In addition, phosphatidylinositol 3 kinase (PI3K) and its downstream protein effector Akt adapt survive in presence oxidative stress. Here we provide evidence for an association between these two defense systems via transcriptional regulation Cu/Zn-superoxide dismutase (Cu/Zn-SOD). PC12 pheochromocytoma expressing active Akt1 exhibit lower ROS levels response hydrogen...
Abstract Dysregulation of the Hippo signaling pathway and consequent YAP1 activation is a frequent event in human malignancies, yet underlying molecular mechanisms are still poorly understood. A pancancer analysis core kinases their candidate regulating molecules revealed few alterations canonical pathway, but very genetic FAT family atypical cadherins. By focusing on head neck squamous cell carcinoma (HNSCC), which displays FAT1 (29.8%), we provide evidence that functional loss results...
Abstract Head and neck squamous cell carcinoma (HNSCC) is the sixth most common cancer worldwide. Tobacco use main risk factor for HNSCC, tobacco-associated HNSCCs have poor prognosis response to available treatments. Recently approved anti-PD-1 immune checkpoint inhibitors showed limited activity (≤20%) in highlighting need identify new therapeutic options. For this, mouse models that accurately mimic complexity of HNSCC mutational landscape tumor environment are urgently needed. Here, we...
Abstract Head and neck squamous cell carcinoma (HNSCC) is a major public health concern. The recent identification of the mTOR complex 1 (mTORC1) signaling pathway as highly prevalent molecular signature underlying HNSCC pathogenesis has provided foundation to search for novel therapeutic approaches prevent treat HNSCC. Here, we asked whether metformin, most widely used medication treatment type II diabetes, which acts in part by stimulating AMP-activated protein kinase (AMPK) thereby...
Abstract Summary: Two studies published in this issue of Cancer Discovery describe the emerging mutational landscape head and neck squamous cell carcinomas (HNSCC) their genomic epigenetic alterations, thus identifying novel actionable cancer drivers predictive biomarkers for targeted therapies. Most alterations HNSCC converge a handful molecular pathways, resulting cell-cycle deregulation, instability, differentiation defects, persistent mitogenic signaling, latter involving aberrant...
Cetuximab, a monoclonal blocking antibody against the epidermal growth factor receptor EGFR, has been approved for treatment of squamous cell carcinomas head and neck (HNSCC). However, only few patients display long-term responses, prompting search cetuximab resistance mechanisms new therapeutic options enhancing effectiveness. Cetuximab-sensitive HNSCC cells were retro-engineered to express PIK3CA RAS oncogenes. These harboring endogenous oncogenes xenografted into mice (n = 10 per group)...
The stria vascularis (SV) generates the endocochlear potential (EP) in inner ear and is necessary for proper hair cell mechanotransduction hearing. While channels belonging to SV types are known play crucial roles EP generation, relatively little about gene regulatory networks that underlie ability of generate maintain EP. Using single nucleus RNA-sequencing, we identify validate rare populations SV. Furthermore, establish a basis understanding molecular mechanisms underlying function by...
Changes in metabolism of macrophages are required to sustain macrophage activation response different stimuli. We showed that the cytokine TGF-β (transforming growth factor–β) regulates glycolysis independently inflammatory production and affects survival mouse models sepsis. During activation, increased expression activity glycolytic enzyme PFKL (phosphofructokinase-1 liver type) promoted but suppressed proinflammatory cytokines. The increase was mediated by an mTOR–c-MYC–dependent pathway,...
This study was designed to elucidate the mechanisms leading down-regulation of Akt/protein kinase B (PKB) survival pathway during H2O2-induced cell death. H2O2 produced early activation Akt/PKB and also DNA damage that followed by stabilization p53 levels, formation reactive oxygen species (ROS), generation ceramide through a glutathione-sensitive neutral sphingomyelinase. These events correlated with long term dephosphorylation subsequent degradation Akt. A membrane-targeted active Akt...
The phosphatidylinositol 3 kinase (PI3K)‐Akt/PKB pathway protects neurons from apoptosis caused by diverse stress stimuli. However, its protective role against the amyloid beta peptide (Aβ), a major constituent of Alzheimer's disease plaques, has not been studied. We investigated effect Aβ‐derived Aβ(25–35) on and Akt survival in PC12 cells. Cells submitted to micromolar concentrations exhibited increased production reactive oxygen species (ROS) morphological alterations consistent with...
The CXC chemokine stromal cell-derived factor-1alpha (SDF-1) binds to CXCR4, a seven-transmembrane G protein-coupled receptor that plays critical role in many physiological processes involve cell migration and fate decisions, ranging from stem homing, angiogenesis, neuronal development immune trafficking. CXCR4 is also implicated various pathological conditions, including metastatic spread human immunodeficiency virus infection. Although SDF-1-induced CXCR4-expressing cells sensitive...
Abstract Purpose: We studied the impact of mTOR signaling inhibition with rapamycin in head and neck squamous cell carcinoma (HNSCC) neoadjuvant setting. The goals were to evaluate pathway as a therapeutic target for patients advanced HNSCC, clinical safety, antitumor, molecular activity administration on HNSCC. Patients Methods: untreated stage II–IVA HNSCC received 21 days (day 1, 15 mg; 2–12, 5 mg) prior definitive treatment surgery or chemoradiation. Treatment responses assessed...
Multiple human malignancies rely on C-X-C motif chemokine receptor type 4 (CXCR4) and its ligand, SDF-1/CXCL12 (stroma cell-derived factor 1/C-X-C 12), to metastasize. CXCR4 inhibitors promote the mobilization of bone marrow stem cells, limiting their clinical application for metastasis prevention. We investigated CXCR4-initiated signaling circuitry identify new potential therapeutic targets. used HeLa cancer cells expressing high levels endogenously. found that CXCL12 promotes migration in...