A5023054173- MicroRNA in disease regulation
- Cancer-related molecular mechanisms research
- RNA modifications and cancer
- Epigenetics and DNA Methylation
- Renal and related cancers
- Circular RNAs in diseases
- Muscle Physiology and Disorders
- Pancreatic and Hepatic Oncology Research
- Renal cell carcinoma treatment
- Galectins and Cancer Biology
- Pancreatitis Pathology and Treatment
- Virus-based gene therapy research
- Pancreatic function and diabetes
- Immune cells in cancer
- Cell Adhesion Molecules Research
- RNA Interference and Gene Delivery
- CAR-T cell therapy research
- Cancer Cells and Metastasis
- Autophagy in Disease and Therapy
- Neurogenetic and Muscular Disorders Research
- RNA Research and Splicing
- Ferroptosis and cancer prognosis
- Atherosclerosis and Cardiovascular Diseases
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Biotin and Related Studies
Ultragenyx Pharmaceutical (United States)
2023
Indiana University – Purdue University Indianapolis
2014-2021
Indiana University School of Medicine
2014-2021
Indiana University Health
2015-2021
Indiana University
2020
University School
2020
Nationwide Children's Hospital
2009-2014
The Ohio State University
2009-2013
UCLouvain
2008
de Duve Institute
2008
miR-122, an abundant liver-specific microRNA (miRNA), regulates cholesterol metabolism and promotes hepatitis C virus (HCV) replication. Reduced miR-122 expression in hepatocellular carcinoma (HCC) correlates with metastasis poor prognosis. Nevertheless, the consequences of sustained loss function vivo have not been determined. Here, we demonstrate that deletion mouse Mir122 resulted hepatosteatosis, hepatitis, development tumors resembling HCC. These pathologic manifestations were...
In prior open-label studies, eteplirsen, a phosphorodiamidate morpholino oligomer, enabled dystrophin production in Duchenne muscular dystrophy (DMD) with genetic mutations amenable to skipping exon 51. The present study used double-blind placebo-controlled protocol test eteplirsen's ability induce and improve distance walked on the 6-minute walk (6MWT).DMD boys aged 7 13 years, confirmed deletions correctable by 51 200 400 m 6 MWT, were randomized weekly intravenous infusions of 30 or 50...
The objective of this study was to establish the feasibility long-term gentamicin dosing achieve stop codon readthrough and produce full-length dystrophin. Mutation suppression codons, successfully achieved in mdx mouse using gentamicin, represents an important evolving treatment strategy Duchenne muscular dystrophy (DMD).Two DMD cohorts received 14-day (7.5mg/kg/day): Cohort 1 (n = 10) patients 2 8) frameshift controls. Two additional were treated (7.5mg/kg) for 6 months: 3 12) dosed weekly...
Abstract Objective: The aim of this study was to attain long‐lasting alpha‐sarcoglycan gene expression in limb‐girdle muscular dystrophy, type 2D (LGMD2D) subjects mediated by adeno‐associated virus (AAV) transfer under control a muscle specific promoter (tMCK). Methods: rAAV1.tMCK.hSGCA (3.25 × 10 11 vector genomes) delivered the extensor digitorum brevis 3 with documented SGCA mutations via double‐blind, randomized, placebo controlled trial. Control sides received saline. blind not broken...
Abstract Objective α‐Sarcoglycan deficiency results in a severe form of muscular dystrophy (limb‐girdle type 2D [LGMD2D]) without treatment. Gene replacement represents strategy for correcting the underlying defect. Questions related to this approach were addressed clinical trial, particularly need immunotherapy and persistence gene expression. Methods A double‐blind, randomized controlled trial using rAAV1.tMCK.hSGCA injected into extensor digitorum brevis muscle was conducted. Control...
A vector delivered into muscles of monkeys generates a natural regulatory molecule, which increases muscle size and strength may be useful therapeutically.
Acquired and intrinsic resistance to receptor tyrosine kinase inhibitors (RTKi) represents a major hurdle in improving the management of clear cell renal carcinoma (ccRCC). Recent reports suggest that drug is driven by tumor adaptation via epigenetic mechanisms activate alternative survival pathways. The histone methyl transferase EZH2 frequently altered many cancers, including ccRCC. To evaluate its role ccRCC RTKi, we established characterized spontaneously metastatic, patient-derived...
Abstract Dense fibrotic stroma associated with pancreatic ductal adenocarcinoma (PDAC) is a major obstacle for drug delivery to the tumor bed and plays crucial role in cancer progression. Current, anti-stromal therapies have failed improve response chemotherapy patient survival. Furthermore, recent studies show that impedes progression its complete ablation accelerates PDAC In an effort understand molecular mechanisms tumor-stromal interactions, using vitro vivo models biopsies, we loss of...
Pancreatic Ductal Adenocarcinoma (PDAC) is a highly lethal malignancy that responds poorly to current therapeutic modalities. In an effort develop novel strategies, we found downregulation of miR-29 in pancreatic cancer cells, and overexpression miR-29a sensitized chemotherapeutic resistant cells gemcitabine, reduced cell viability, increased cytotoxicity. Furthermore, blocked autophagy flux, as evidenced by accumulation autophagosomes markers, LC3B p62, decrease autophagosome-lysosome...
MicroRNA-29 (miR-29) is a critical regulator of fibroinflammatory processes in human diseases. In this study, we found decrease miR-29a experimental and chronic pancreatitis, leading us to investigate the regulatory role miR-29a/b1 cluster acute pancreatitis (AP) utilizing conditional miR-29a/b1–KO mouse model. miR-29a/b1-sufficient (WT) -deficient (KO) mice were administered supramaximal caerulein induce AP characterized at different time points, an array IHC biochemical analyses for...
Pancreatic ductal adenocarcinoma (PDAC) is an intractable cancer with a dismal prognosis. miR-29a commonly downregulated in PDAC; however, mechanisms for its loss and role still remain unclear. Here, we show that PDAC, repression of directly mediated by MYC via promoter activity. RNA sequencing analysis, integrated miRNA target prediction, identified global downstream targets PDAC. Target enrichment coupled gene ontology survival correlation analyses the top five miR-29a-downregulated genes...
Recombinant adeno-associated virus (rAAV)-mediated gene delivery shows promise to transduce the pancreas, but safety/efficacy in a neoplastic context is not well established. To identify an ideal AAV serotype, route, and vector dose assess safety, we have investigated use of three serotypes (6, 8, 9) expressing GFP self-complementary (sc) under EF1α promoter (scAAV.GFP) following systemic or retrograde pancreatic intraductal delivery. Systemic scAAV9.GFP transduced pancreas with high...
Recent in vitro studies suggest that CAPN3 deficiency leads initially to accelerated myofiber formation followed by depletion of satellite cells (SC). In normal muscle, up-regulation miR-1 and miR-206 facilitates transition from proliferating SCs differentiating myogenic progenitors.We examined the histopathological stages, Pax7 SC content, muscle-specific microRNA expression biopsy specimens well-characterized LGMD 2A patients gain insight into disease pathogenesis.Three distinct stages...
Abstract Colorectal cancer (CRC) is the fourth leading cause of cancer-related deaths worldwide. Liver metastasis major CRC patient mortality, occurring in 60% patients with no effective therapies. Although studies have indicated role miRNAs CRC, an in-depth miRNA expression analysis essential to identify clinically relevant and understand their potential targeting liver metastasis. Here we analyzed expressions 405 tumors from publicly available colorectal genome sequencing project database....
Abstract MicroRNA (miRNA) are short non-coding RNA molecules that regulate multiple cellular processes, including development, cell differentiation, proliferation and death. Nevertheless, little is known on whether miRNA control the same gene networks in different tissues. miR-709 an abundant expressed ubiquitously. Through transcriptome analysis, we have identified targets of hepatocytes. represses genes implicated cytoskeleton organization, extracellular matrix attachment fatty acid...
Abstract Background Pancreatic ductal adenocarcinoma (PDAC) is one of the most aggressive forms malignancies with a nearly equal incidence and mortality rates in patients. stellate cells (PSCs) are critical players PDAC microenvironment to promote aggressiveness pathogenesis disease. Dysregulation microRNAs (miRNAs) have been shown play significant role progression PDAC. Earlier, we observed PSC-specific downregulation miR-29a pancreas, however, mechanism action molecule PSCs still be...
Background and Objectives Hepatocellular carcinoma (HCC) in patients with hepatitis B virus (HBV) exhibit lower tumor microRNA‐26a (miR‐26a) expression which is associated worse outcomes. It unknown if similar miR‐26a loss occurs HCC developed other liver diseases. We examined its impact on recurrence mortality a North American cohort. Methods MiR‐26a levels from surrounding nontumor tissue 186 subjects were collected. defined of as <1‐fold that the adjacent tissue. Results Viral (42%;...
MicroRNA-29a (miR-29a) is a well characterized fibro-inflammatory molecule and its aberrant expression linked to variety of pathological liver conditions. The long-term effects high-fat diet (HFD) in combination with different levels EtOH consumption on miR-29a pathobiology are unknown. Mice at 8 weeks age were divided into five groups (calorie-matched plus water (CMD) as control group, HFD disease 2% (HFD + E), 10% E, 20% E intervention groups) fed for 4, 13, 26, or 39 weeks. At each time...
Abstract Background Pancreatic ductal adenocarcinoma (PDAC) is one of the most aggressive forms malignancies with a nearly equal incidence and mortality rates in patients. stellate cells (PSCs) are critical players PDAC microenvironment to promote aggressiveness pathogenesis disease. Dysregulation microRNAs (miRNAs) have been shown play significant role progression PDAC. Earlier, we observed PSC-specific downregulation miR-29a pancreas, however, mechanism action molecule PSCs still be...