A5086145770- Chromatin Remodeling and Cancer
- Ovarian cancer diagnosis and treatment
- Cancer Mechanisms and Therapy
- Cancer Cells and Metastasis
- Peptidase Inhibition and Analysis
- Cancer-related gene regulation
- Virus-based gene therapy research
- Signaling Pathways in Disease
- MicroRNA in disease regulation
- Cancer, Hypoxia, and Metabolism
- Neuroblastoma Research and Treatments
- Cytokine Signaling Pathways and Interactions
- Pregnancy and preeclampsia studies
- Extracellular vesicles in disease
- FOXO transcription factor regulation
- Sarcoma Diagnosis and Treatment
- Digestive system and related health
- Inflammatory Bowel Disease
- Thermal Regulation in Medicine
- Mechanisms of cancer metastasis
- Skin Diseases and Diabetes
- Circular RNAs in diseases
- Infant Nutrition and Health
- Fungal Infections and Studies
- Zebrafish Biomedical Research Applications
Gundersen Health System
2020-2024
AstraZeneca (Sweden)
2024
Indiana University – Purdue University Indianapolis
2012-2020
Indiana University School of Medicine
2012-2020
University of Notre Dame
2012-2020
Indiana University Health
2012-2020
Indiana University South Bend
2012-2020
Mike and Josie Harper Cancer Research Institute
2015-2020
Indiana University
2012-2020
Cancer Research Institute
2004-2017
Placental development initially occurs in a low-oxygen (O2) or hypoxic environment. In this report we show that two hypoxia-inducible factors (HIFs), HIF1α and HIF2α, are essential for determining murine placental cell fates. HIF is heterodimer composed of HIFα HIFβ (ARNT) subunits. Placentas from Arnt−/− Hif1α−/− Hif2α−/− embryos exhibit defective vascularization aberrant fate adoption. regulation Mash2 promotes spongiotrophoblast differentiation, prerequisite trophoblast giant...
Abstract Epidermal growth factor (EGF) receptor (EGFR) is frequently elevated in epithelial ovarian cancer, and E-cadherin expression often reduced advanced disease. In this study, we investigated a mechanism by which EGFR activation promotes disruption of adherens junctions through induction matrix metalloproteinase 9 (MMP-9). We show that down-modulates E-cadherin, broad spectrum MMP inhibition ameliorates EGF-stimulated junctional loss protein. MMP-9 involvement EGF-dependent...
The epithelial-to-mesenchymal transition (EMT) that occurs during embryonic development is recapitulated tumor metastasis. Important regulators of this process include growth factors, transcription and adhesion molecules. New evidence suggests microRNA (miRNA) activity contributes to metastatic progression EMT; however, the mechanisms leading altered miRNA expression cancer remain poorly understood. Importantly, overexpression epidermal factor receptor (EGFR) in ovarian correlates with poor...
Hypoxia Inducible Factor (HIF), consisting of HIF1alpha and ARNT (HIF1beta) subunits, activates multiple genes in response to oxygen (O(2)) deprivation. Arnt(-/-) mice exhibit substantial defects blood cell vessel development. We demonstrate that hypoxia accelerates the expression Brachyury (a mesoderm-specific transcription factor), BMP4 mesoderm-promoting growth factor) FLK1 marker hemangioblasts, bipotential progenitor endothelial hematopoietic cells) differentiating ES cultures....
Hypoxia-inducible factor (HIF)-deficient placentas exhibit a number of defects, including changes in cell fate adoption, lack fetal angiogenesis, hypocellularity, and poor invasion into maternal tissue. HIF is heterodimeric transcription consisting alpha beta aryl hydrocarbon receptor nuclear translocator or ARNT) subunits. We used undifferentiated trophoblast stem (TS) cells to characterize HIF-dependent adhesion, migration, invasion. Arnt(-/-) Hifalpha(-/-) TS reduced adhesion migration...
Cancer stem cells (CSCs) are an attractive therapeutic target due to their predicted role in both metastasis and chemoresistance. One of the most commonly agreed on markers for ovarian CSCs is cell surface protein CD133. CD133+ have increased tumorigenicity, resistance chemotherapy, metastasis. Therefore, we were interested defining how CD133 regulated whether it has a tumor Previously found that overexpression transcription factor, ARID3B, expression PROM1 (CD133 gene) cancer vitro...
Elevated expression of the epidermal growth factor (EGF) receptor (EGFR) is detected in human ovarian tumors and associated with decreased recurrence-free overall survival. EGFR activation affects tumor progression part by promoting invasion through induction prometastatic matrix metalloproteinases (MMP). PEA3, an ETS family transcription factor, elevated advanced metastatic cancer regulates MMPs various cell types, therefore, we investigated whether PEA3 required for EGFR-dependent MMP...
The DNA-binding protein AT-Rich Interactive Domain 3B (ARID3B) is elevated in ovarian cancer and increases tumor growth a xenograft model of cancer. However, relatively little known about ARID3B's function. In this study we perform the first genome wide screen for ARID3B direct target genes regulated pathways. We identified confirmed numerous by chromatin immunoprecipitation (ChIP) followed microarray quantitative RT-PCR. Using motif-finding algorithms, characterized binding site ARID3B,...
Pragmatic clinical research is part of five focus areas the Challenges in IBD document, which also includes preclinical human mechanisms, environmental triggers, novel technologies, and precision medicine. The document provides a comprehensive overview current gaps inflammatory bowel diseases (IBD) delivers actionable approaches to address them. It result multidisciplinary input from scientists, clinicians, patients, funders, represents valuable resource for patient centric prioritization....
// Lynn Roy 1 , Serene J. Samyesudhas Martin Carrasco Jun Li 2 Stancy Joseph Richard Dahl 3 and Karen D. Cowden 1,4,5 Department of Biochemistry Molecular Biology, Indiana University School Medicine, South Bend, Applied Computational Mathematics Statistics, Notre Dame, Microbiology Immunology, 4 Chemistry Eck Institute for Global Health, Dame University, 5 Melvin Bren Simon Cancer Center, Indianapolis, Correspondence: email: Keywords : Ovarian cancer, transcription factor, cancer stem cells,...
Ovarian cancer is the most lethal gynecological malignancy. Poor overall survival, particularly for patients with high grade serous (HGS) ovarian cancer, are often attributed to late stage at diagnosis and relapse following chemotherapy. HGS a heterogenous disease in that few genes consistently mutated between patients. Additionally, characterized by genomic instability. For these reasons personalized approaches may be necessary effective treatment cure. Understanding molecular mechanisms...
Abstract Macrophages are critical for regulating inflammatory responses. Environmental signals polarize macrophages to either a proinflammatory (M1) state or an anti-inflammatory (M2) state. We observed that the microRNA (miRNA) cluster mirn23a, coding miRs-23a, -27a, and -24-2, regulates mouse macrophage polarization. Gene expression analysis of mirn23a-deficient myeloid progenitors revealed decrease in TLR IFN signaling. Mirn23a−/− bone marrow–derived (BMDMs) have attenuated response LPS,...
Ovarian cancer (OC) cells survive in the peritoneal cavity a complex microenvironment composed of diverse cell types. The interaction between tumor and non-malignant is crucial to success metastatic process. Macrophages activate pro-metastatic signaling pathways ovarian (OCCs), induce angiogenesis, orchestrate suppressive immune response by releasing anti-inflammatory cytokines. Understanding will enhance our ability combat growth dissemination. When co-cultured with OCCs, macrophages...
Alternative splicing is a common occurrence in many cancers. linked with decreased apoptosis and chemoresistance cancer cells. We previously demonstrated that ARID3B, member of the AT-rich interactive domain (ARID) family DNA binding proteins, overexpressed ovarian cancer. Therefore we wanted to assess effect ARID3B splice forms on cell viability. identified novel form gene (designated as Sh), which lacks C-terminal exons 5–9 present full-length isoform (ARID3B Fl). Fl expressed variety...
Cancer stem cells (CSCs) are defined as a subset of slow cycling and undifferentiated that divide asymmetrically to generate highly proliferative, invasive, chemoresistant tumor cells. Therefore, CSCs an attractive population target therapeutically. predicted contribute number types malignancies including those in the blood, brain, lung, gastrointestinal tract, prostate, ovary. Isolating enriching cell for will enable researchers study properties, genetics, therapeutic response CSCs. We...
Uterine carcinosarcoma (UCS) is a rare but aggressive endometrial cancer. Survival outcomes for women diagnosed with UCS remain poor lower survival than those of endometrioid or high-grade serous uterine cancers. The histopathological hallmark the presence both sarcomatous and carcinomatous elements. rates have not improved over 40 years; therefore, there profound need to identify new treatments. To investigate novel chemotherapy treatment combinations UCS, we generated patient-derived...
Precision imaging is needed to realize precision medicine in cancer detection and treatment. Molecular offers the ability target identify tumors, associated abnormalities, specific cell populations with overexpressed receptors. Nuclear radionuclide probes provide high sensitivity but subject patient a radiation dose limited spatiotemporal information, requiring combined computed tomography (CT) for anatomic imaging. Therefore, nanoparticle contrast agents have been designed enable molecular...
Arid3a and Arid3b belong to a subfamily of ARID (AT-rich interaction domain) transcription factors. The Arid family is involved in regulating chromatin accessibility, proliferation, differentiation. are closely related share unique REKLES domain that mediates their homo- hetero-multimerization. was originally isolated as B cell factor binding the AT rich matrix attachment regions (MARS) immunoglobulin heavy chain intronic enhancer. Deletion results highly penetrant embryonic lethality with...
Feeding interrupts the migrating myoelectric complex in most mammals. This study aimed to assess whether resumption of human duodenum after eating was related gastrointestinal transit meal. Five healthy subjects participated study. After a radiolabelled test meal consisting mixed liquid and solids, duodenal activity were determined simultaneously. In spite considerable variation entire gastric emptying time between (range 2.5-5.0 hours), significant correlation found completion phase III...