A5006241712- Developmental Biology and Gene Regulation
- Virus-based gene therapy research
- Neonatal Respiratory Health Research
- Cystic Fibrosis Research Advances
- RNA Interference and Gene Delivery
- Neurobiology and Insect Physiology Research
- Bacterial Genetics and Biotechnology
- Axon Guidance and Neuronal Signaling
- Herpesvirus Infections and Treatments
- Genetics, Aging, and Longevity in Model Organisms
- Cancer-related gene regulation
- RNA regulation and disease
- Click Chemistry and Applications
- Lipid Membrane Structure and Behavior
- Advanced biosensing and bioanalysis techniques
- Cytomegalovirus and herpesvirus research
- Monoclonal and Polyclonal Antibodies Research
- ATP Synthase and ATPases Research
- Genomics and Chromatin Dynamics
- Physiological and biochemical adaptations
- RNA and protein synthesis mechanisms
- Protein Kinase Regulation and GTPase Signaling
- CRISPR and Genetic Engineering
- Inhalation and Respiratory Drug Delivery
- Wnt/β-catenin signaling in development and cancer
Sanofi (United States)
2019-2020
University of Massachusetts Chan Medical School
2020
Framingham State University
2020
Université Paris Cité
2006-2009
Harvard University
2007-2009
Université Paris-Sud
2007-2009
Massachusetts General Hospital
2006-2007
Collège de France
2006
Liver-directed gene therapy with adeno-associated virus (AAV) vectors effectively treats mouse models of lysosomal storage diseases (LSDs). We asked whether these results were likely to translate patients. To understand what extent preexisting anti-AAV8 antibodies could impede AAV8-mediated liver transduction in primates, commonly preexposed AAV, we quantified the effects on and subsequent transgene expression nonhuman primate (NHP) models. Using highest viral dose previously reported a...
Abstract Notch signaling regulates multiple developmental processes and is implicated in various human diseases. Through use of the transcriptional co-activator mastermind, we conducted a screen for signal modifiers using Exelixis collection insertional mutations, which affects ∼50% Drosophila genome, recovering 160 genes never before associated with Notch, extending previous roster that interact functionally pathway mastermind. As molecular identity most recovered known, gene ontology (GO)...
In mice, liver-restricted expression of lysosomal enzymes from adeno-associated viral serotype 8 (AAV8) vectors results in reduced antibodies to the expressed proteins. To ask whether this result might translate patients, nonhuman primates (NHPs) were injected systemically with AAV8 encoding α-galactosidase A (α-gal). As sustained monkeys attenuated antibody responses α-gal. However, effect was not robust, and α-gal levels 1-2 logs lower than those achieved male mice at same vector dose....
Deregulation of energy metabolism by external interventions or mutations in metabolic genes can extend lifespan a wide range species. We describe Drosophila melanogaster that confer resistance to oxidative stress and display longevity phenotype. These phenotypes are associated with molecular lesions hitherto uncharacterized gene we named Enigma. show Enigma encodes mitochondrial protein homology enzymes the β-oxidation fatty acids this locus affect lipid homeostasis. Our analysis provides...
Metazoans use a handful of highly conserved signaling pathways to create backbone that governs development. How these few signals have such versatile action likely depends upon the larger-scale network they form through integration, as exemplified by cross-talk between Notch and receptor tyrosine kinase (RTK) pathways. We examined transcriptional output Notch-RTK during Drosophila development present in vivo data supporting role for selected mutually regulated genes signal integration....
Central nervous system (CNS)-directed gene therapy with recombinant adeno-associated virus (AAV) vectors has been used effectively to slow disease course in mouse models of several neurodegenerative diseases. However, these were typically tested mice without prior exposure the virus, an immunological scenario unlikely be duplicated human patients. Here, we examined impact pre-existing immunity on AAV-mediated delivery CNS normal and diseased mice. Antibody levels brain tissue determined 0.6%...
Cystic Fibrosis (CF), an inherited multi-system disease, is caused by mutations in the Transmembrane Conductance Regulator (CFTR) that disrupt its ability to secrete anions from epithelia. Recovery of functional anion secretion may be curative for CF, so different components ion transport machinery have become attractive therapeutic targets. Several members SLC26 transporter family been linked epithelial flux, some through putative interactions with CFTR. Using a small-scale qPCR screen, we...
Abstract Cystic fibrosis (CF) results from mutations within the gene encoding Fibrosis Transmembrane Conductance Regulator (CFTR), a transmembrane chloride channel found on apical surface of epithelial cells. The most common CF-causing mutation in deletion phenylalanine 508 (ΔF508-CFTR), residue normally NBD1 domain. Loss F508 causes to be less thermodynamically stable and prevents proper tertiary folding CFTR. As result, CFTR is not properly trafficked cell surface. Recently, progress has...