A5044442671- MicroRNA in disease regulation
- Liver physiology and pathology
- Cancer Mechanisms and Therapy
- Cancer-related molecular mechanisms research
- Circular RNAs in diseases
- Glioma Diagnosis and Treatment
- Cancer, Hypoxia, and Metabolism
- RNA modifications and cancer
- Mitochondrial Function and Pathology
- PI3K/AKT/mTOR signaling in cancer
- Cancer Cells and Metastasis
- Microtubule and mitosis dynamics
- RNA Research and Splicing
- Cell Adhesion Molecules Research
- Advanced Breast Cancer Therapies
- Multiple Myeloma Research and Treatments
- Ion channel regulation and function
- Neuropeptides and Animal Physiology
- Neuroblastoma Research and Treatments
- ATP Synthase and ATPases Research
- Autophagy in Disease and Therapy
- Cancer-related Molecular Pathways
- Hedgehog Signaling Pathway Studies
- RNA regulation and disease
- HER2/EGFR in Cancer Research
University of Virginia
2016-2025
Johns Hopkins University
1999-2024
Johns Hopkins Medicine
1999-2024
National Cancer Institute
2023-2024
University of Virginia Cancer Center
2011-2024
University of Maryland, Baltimore
2024
Dow University of Health Sciences
2024
National Institutes of Health
2024
University of Virginia Health System
2008-2016
Brigham and Women's Hospital
2014
microRNAs are noncoding RNAs inhibiting expression of numerous target genes, and a few have been shown to act as oncogenes or tumor suppressors. We show that microRNA-7 (miR-7) is potential suppressor in glioblastoma targeting critical cancer pathways. miR-7 potently suppressed epidermal growth factor receptor expression, furthermore it independently inhibited the Akt pathway via upstream regulators. was down-regulated versus surrounding brain, with mechanism involving impaired processing....
Abstract MicroRNA-34a (miR-34a) is a transcriptional target of p53 that down-regulated in some cancer cell lines. We studied the expression, targets, and functional effects miR-34a brain tumor cells human gliomas. Transfection c-Met glioma medulloblastoma Notch-1, Notch-2, CDK6 protein expressions cells. expression inhibited reporter activities Notch-1 Notch-2 3′-untranslated region stem Analysis specimens showed glioblastoma tissues as compared with normal mutant gliomas wild-type levels...
We recently found that microRNA-34a (miR-34a) is downregulated in human glioma tumors as compared to normal brain, and miR-34a levels mutant-p53 gliomas were lower than wildtype-p53 tumors. showed expression medulloblastoma cells inhibits cell proliferation, G1/S cycle progression, survival, migration invasion, but astrocytes does not affect survival cycle. uncovered the oncogenes c-Met, Notch-1 Notch-2 direct targets of are inhibited by transfection. c-Met specimens inversely correlate with...
Little is known of microRNA interactions with cellular pathways. Few reports have associated microRNAs the Notch pathway, which plays key roles in nervous system development and brain tumors. We previously implicated pathway gliomas, most common aggressive While investigating mediators, we noted microRNA-326 was upregulated following Notch-1 knockdown. This neuronally expressed not only suppressed by but also inhibited proteins activity, indicating a feedback loop. MicroRNA-326 downregulated...
DMT1 (divalent metal transporter 1) is a hydrogen-coupled divalent with substrate preference for iron, although the protein when expressed in frog oocytes transports broad range of metals, including toxic metals cadmium and lead. Wild-type Caco-2 cells displayed saturable transport lead iron that was stimulated by acid. Cadmium manganese inhibited but zinc did not. The involvement examined establishing clonal knockdown control cell lines. Knockdown lines much lower levels mRNA smaller V max...
Great interest persists in useful prognostic and therapeutic targets glioblastoma. In this study, we report the definition of miRNA (miR)-148a as a novel oncomiR miR-148a expression was elevated human glioblastoma specimens, cell lines, stem cells (GSC) compared with normal brain astrocytes. High levels were risk indicator for patient survival. Functionally, increased growth, survival, migration, invasion GSCs promoted GSC neurosphere formation. Two direct identified, EGF receptor (EGFR)...
Abstract Although diacylglycerol kinase α (DGKα) has been linked to several signaling pathways related cancer cell biology, it neglected as a target for therapy. The attenuation of DGKα activity via DGKα-targeting siRNA and small-molecule inhibitors R59022 R59949 induced caspase-mediated apoptosis in glioblastoma cells other cancers, but lacked toxicity noncancerous cells. We determined that mTOR hypoxia-inducible factor-1α (HIF-1α) are key targets inhibition, addition its regulation...
Abstract Glioblastoma (GBM) stem-like cells (GSC) promote tumor initiation, progression, and therapeutic resistance. Here, we show how GSCs can be targeted by the FDA-approved drug mibefradil, which inhibits T-type calcium channel Cav3.2. This was highly expressed in human GBM specimens enriched GSCs. Analyses of The Cancer Genome Atlas REMBRANDT databases confirmed upregulation Cav3.2 a subset tumors showed that overexpression associated with worse prognosis. Mibefradil treatment or...
Abstract Brain metastasis (BM) is the most common type of brain tumor and frequently foreshadows disease progression poor overall survival with patients having a median 6 months. 70,000 new cases BM are diagnosed each year in United States (US) incidence rate for increasing improved detection. MicroRNAs (miRNAs) small non-coding RNAs that serve as critical regulators gene expression can act powerful oncogenes suppressors. MiRNAs have been heavily implicated cancer proposed biomarkers or...
The multifunctional growth factor scatter factor/hepatocyte (SF/HGF) and its receptor c-met have been implicated in the genesis, malignant progression, chemo/radioresistance of multiple human malignancies, including gliomas. We examined antitumor effects targeting SF/HGF expression pre-established glioma xenografts by using novel chimeric U1snRNA/ribozymes. Transient anti-SF/HGF anti-c-met U1snRNA/ribozymes inhibited expression, activation, tumor cell migration, anchorage-independent colony...
BACKGROUND: Expression of scatter factor (SF), also known as hepatocyte growth (HGF), and its receptor, c-met, is often associated with malignant progression human tumors, including gliomas. Overexpression SF/HGF in experimental gliomas enhances tumorigenicity tumor-associated angiogenesis (i.e., new blood vessels). However, the role endogenous or c-met expression has not been examined directly. In this study, we tested hypothesis that glioblastomas can be SF/HGF–c-met dependent a reduction...
Abstract Purpose: Resistance to current cytotoxic therapies limits the treatment of most solid malignancies. This results, in part, from overactivation receptor tyrosine kinases and their downstream pathways tumor cells associated vasculature. In this report, we ask if targeting multifunctional mitogenic, cytoprotective, angiogenic scatter factor/hepatocyte growth factor (SF/HGF)/c-Met pathway potentiates antitumor responses γ-radiation. Experimental Design: Endogenous expression SF/HGF...
Glioblastoma is the most common and lethal primary brain tumor. Tumor initiation recurrence are likely caused by a sub-population of glioblastoma stem cells, which may derive from mutated neural precursor cells. Since CD133 cell marker for both normal glioblastoma, to better understand formation recurrence, we looked dys-regulated microRNAs in human CD133+ cells as opposed isolated brain. Using FACS sorting low-passage samples followed microRNA microarray analysis, found 43 that were three...
Chordomas are rare malignant tumors that originate from the notochord remnants and occur in skull base, spine sacrum. Due to a very limited understanding of molecular pathogenesis chordoma, there no adjuvant therapies besides surgical resection radiation therapy. microRNAs (miRNAs) small noncoding regulatory RNA molecules with critical roles cancer. The role miRNAs chordomas is mostly unknown. We uncover microRNA-608 (miR-608) microRNA-34a (miR-34a) as novel tumor suppressive regulate...
Long noncoding RNAs (lncRNAs) have emerged as a major regulator of cell physiology, but many which no known function. CDKN1A/p21 is an important inhibitor the cell-cycle, DNA damage response and effector tumor suppressor p53, playing crucial role in development prevention. In order to identify for progression, we performed siRNA screen human lncRNAs required proliferation, identified novel lncRNA, APTR, that acts trans repress promoter independent p53 promote proliferation. APTR associates...
Abstract Purpose: Glioblastoma (GBM) is a deadly brain tumor marked by dysregulated signaling and aberrant cell-cycle control. Molecular analyses have identified that the CDK4/6-Rb-E2F axis in about 80% of GBMs. Single-agent CDK4/6 inhibitors failed to provide durable responses GBM, suggesting need combine them with other agents. We investigate efficacy combination inhibition mTOR against GBM. Experimental Design: Preclinical vitro vivo assays using primary GBM cell lines were performed....
Background Each year, over 16,000 patients die from malignant brain cancer in the US. Long noncoding RNAs (lncRNAs) have recently been shown to play critical roles regulating neurogenesis and tumor progression. To better understand role of lncRNAs cancer, we performed a global analysis identify characterize all annotated novel both grade II III gliomas as well IV glioblastomas (glioblastoma multiforme [GBM]). Methods Findings We determined expression 650 70 normal tissue RNA sequencing...
Abstract Cancer cells rely on mitochondrial functions to regulate key survival and death signals. How cancer autophagy (mitophagy) in the tumor microenvironment as well utilize mitophagy a signal is still not understood. Here, we elucidate mechanism of NIX-mediated within hypoxic region glioblastoma, most malignant brain tumor. NIX was overexpressed pseudopalisading that envelop hypoxic–necrotic regions, expression robust patient-derived glioblastoma tissues stem cells. required for hypoxia...
Abstract Glioblastoma is a deadly cancer, with no effective therapies. Better understanding and identification of selective targets are urgently needed. We found that advillin (AVIL) overexpressed in all the glioblastomas we tested including glioblastoma stem/initiating cells, but hardly detectable non-neoplastic astrocytes, neural stem cells or normal brain. Glioma patients increased AVIL expression have worse prognosis. Silencing nearly eradicated culture, dramatically inhibited vivo...