A5078686725- RNA Interference and Gene Delivery
- Skin and Cellular Biology Research
- RNA and protein synthesis mechanisms
- Silk-based biomaterials and applications
- RNA Research and Splicing
- Advancements in Transdermal Drug Delivery
- RNA modifications and cancer
- Advanced biosensing and bioanalysis techniques
- Cellular Mechanics and Interactions
- Viral Infections and Immunology Research
- Advanced Fluorescence Microscopy Techniques
- Virus-based gene therapy research
- Nail Diseases and Treatments
- Lipid Membrane Structure and Behavior
- Photoacoustic and Ultrasonic Imaging
- Plant Reproductive Biology
- MicroRNA in disease regulation
- bioluminescence and chemiluminescence research
- Dermatological and Skeletal Disorders
- Viral Infectious Diseases and Gene Expression in Insects
- Wnt/β-catenin signaling in development and cancer
- Immunotherapy and Immune Responses
- Optical Coherence Tomography Applications
- Transgenic Plants and Applications
- Polyamine Metabolism and Applications
Stanford University
2008-2013
Stanford Medicine
2011-2013
SomaGenics (United States)
2005-2008
University of Utah
2005
Brigham Young University
1987-2003
University of Alberta
2001
McGill University
1996
Molecular Oncology (United States)
1996
Harvard–MIT Division of Health Sciences and Technology
1994-1995
Massachusetts Institute of Technology
1994
Significance Extracellular vesicle (EV)-mediated transfer of macromolecules may play a key role in cellular communication and have utility directed molecular therapies. In addition, the EV packaged biomolecules serum potential for diagnosing cancer determining its likelihood metastasis. EVs are heterogeneous there many outstanding questions associated with biogenesis, uptake, fate transferred molecules recipient cells. fact, function, characterization, even nomenclature being refined. Here...
The structure of m7GpppN (where N is any nucleotide), termed cap, present at the 5' end all eukaryotic cellular mRNAs (except organellar). initiation factor 4E (eIF-4E) binds to cap and facilitates formation translation complexes. eIF-4E implicated in control cell growth, as its overexpression causes malignant transformation rodent cells deregulates HeLa growth. It was suggested that results enhanced poorly translated encode growth-promoting proteins. Indeed, expression several proteins,...
Regulation of the cell cycle is orchestrated by cyclins and cyclin-dependent kinases. We have demonstrated previously that overexpression eukaryotic translation initiation factor 4E (eIF-4E) in NIH 3T3 cells growing 10% fetal calf serum leads to highly elevated levels cyclin D1 protein without significant increase mRNA levels, suggesting a post-transcriptional mechanism involved. (Rosenwald, I. B., Lazaris-Karatzas, A., Sonenberg, N., Schmidt, E. V.(1993) Mol. Cell. Biol. 13, 7358-7363). In...
Significance Here we report that keratin 16 (Krt16), a type I intermediate filament cytoskeletal protein, is an integral and functionally important component of genetic network regulating danger signals, innate immunity, barrier function in skin epidermis. Our findings help explain the pathogenesis conspicuous lesions arising disorders caused by mutations Krt16, such as pachyonychia congenita focal palmoplantar keratoderma, diseases which Krt16 induced misregulated, psoriasis cancer.
Small interfering RNA (siRNA) is a highly potent drug in gene-based therapy with challenge of being delivered sustained manner. Nanoparticle delivery systems allow for incorporating and controlled release therapeutic payloads. We demonstrate that solid lipid nanoparticles can incorporate provide siRNA. Tristearin nanoparticles, made by nanoprecipitation, were loaded siRNA (4.4-5.5 wt % loading ratio) using hydrophobic ion pairing approach employs the cationic DOTAP. Intradermal injection...
The polyanionic nature of oligonucleotides and their enzymatic degradation present challenges for the use siRNA in research therapy; among most notable these is clinically relevant delivery into cells. To address this problem, we designed synthesized first members a new class guanidinium-rich amphipathic oligocarbonates that noncovalently complex, deliver, release cells, resulting robust knockdown target protein synthesis vitro as determined using dual-reporter system. organocatalytic...
Ribosomal protein L32 mRNA moved from messenger ribonucleoprotein particles into polysomes following serum activation of quiescent Swiss 3T3 cells. This redistribution the a translationally active state began by 1 h and was complete 3 after activation. In contrast, actin showed no translational control, being found predominantly in both activated cultures. The phosphorylation eukaryotic initiation factor (eIF) 4E, which binds caps, examined parallel. eIF-4E elevated reached peak 3-5 h....
RNA interference offers enormous potential to develop therapeutic agents for a variety of diseases. To assess the stability siRNAs under conditions relevant clinical use with particular emphasis on topical delivery considerations, study three different unmodified was performed. The results indicate that neither repeated freeze/thaw cycles, extended incubations (over 1 year at 21 degrees C), nor shorter high temperatures (up 95 C) have any effect siRNA integrity as measured by nondenaturing...
The mRNA encoding ribosomal protein L32 redistributes from untranslated subribosomal particles into polysomes after mitogenic activation of quiescent T-lymphocytes and fibroblasts. To identify the regions which are important in regulating its cytoplasmic location we constructed a plasmid containing murine cDNA under control Rous sarcoma virus (RSV) long terminal repeat promoter introduced this construct 3T3 transcribed RSV-L32 redistributed response to manner similar endogenous mRNA. A...
Despite rapid progress in the development of potent and selective small interfering RNA (siRNA) agents for skin disorders, translation to clinic has been hampered by lack effective, patient-friendly delivery technologies. The stratum corneum poses a formidable barrier efficient large and/or charged macromolecules including siRNAs. Intradermal siRNA injection results effective knockdown targeted gene expression but is painful effects are localized site. use microneedle arrays represents less...
Palmoplantar keratoderma (PPK) are debilitating lesions that arise in individuals with pachyonychia congenita (PC) and feature upregulation of danger-associated molecular patterns skin barrier regulators. The defining features PC-associated PPK reproduced mice null for keratin 16 (Krt16), which is commonly mutated PC patients. Here, we have shown onset preceded by oxidative stress footpad Krt16–/– correlates an inability keratinocytes to sustain nuclear factor erythroid–derived 2 related...
Treatment and prevention of hepatitis C virus (HCV) infections remain a major challenge for controlling this worldwide health problem; existing therapies are only partially effective no vaccine is currently available. RNA interference offers the potential novel therapeutic approach treating HCV infections. Toward end, we evaluated small hairpin interfering RNAs (shRNAs) targeting conserved internal ribosome entry site (IRES) element genome their ability to control gene expression in human...
Abstract Recent reports suggest that regulation of IL-1 beta gene expression in human monocytes may include translation level as well transcription control mechanisms. We studied PBMC stimulated with recombinant complement protein C5a or LPS. mRNA was expressed by C5a-treated PBMC, but very little no could be detected ELISA Western blot analysis using a polyclonal Ab reacts equally pro-IL-1 and processed mature beta. LPS-treated cells produced both protein. Velocity sedimentation revealed,...
Hepatitis C virus (HCV) is a leading cause of liver cirrhosis and hepatocellular carcinoma worldwide. Currently available treatment options are limited efficacy, there an urgent need for development alternative therapies. RNA interference (RNAi) natural mechanism by which small interfering (siRNA) or short hairpin (shRNA) can mediate degradation target molecule in sequence-specific manner. In this study, we screened vitro-transcribed 25-bp shRNAs targeting the internal ribosome entry site...