A5054419089- RNA Interference and Gene Delivery
- Advanced biosensing and bioanalysis techniques
- Cytokine Signaling Pathways and Interactions
- Cardiac Fibrosis and Remodeling
- Immune Cell Function and Interaction
- Virus-based gene therapy research
- T-cell and B-cell Immunology
- Biochemical effects in animals
- Animal Nutrition and Physiology
- Viral Infections and Immunology Research
- Infrared Thermography in Medicine
- Nerve injury and regeneration
- Lipid Membrane Structure and Behavior
- DNA and Nucleic Acid Chemistry
- Immunotherapy and Immune Responses
- Eosinophilic Esophagitis
- Nanoparticle-Based Drug Delivery
- Signaling Pathways in Disease
- Immune Response and Inflammation
- Autoimmune and Inflammatory Disorders
- Inflammatory Bowel Disease
- Nuclear Receptors and Signaling
Center for Systems Biology
2017-2019
Harvard University
2017-2019
Massachusetts General Hospital
2017-2019
University of Washington
2013-2015
Seattle University
2014
Scripps Research Institute
2014
New England College of Optometry
2012-2013
Cedars-Sinai Medical Center
2009
Myocardial infarction (MI) elicits massive inflammatory leukocyte recruitment to the heart. Here, we hypothesized that excessive invasion leads heart failure and death during acute myocardial ischemia. We found shortly transiently after onset of ischemia, human mouse cardiac fibroblasts produce granulocyte/macrophage colony-stimulating factor (GM-CSF) acts locally distally generate recruit proteolytic cells. In heart, fibroblast-derived GM-CSF alerts its neighboring myeloid cells attract...
Nanoparticle morphology has been shown to affect cellular uptake, but there are few studies investigating the impact of particle shape on biologic drug delivery. Recently, our group synthesized a series N-(2-hydroxypropyl) methacrylamide (HPMA)-oligolysine brush polymers for nucleic acid delivery that varied in oligolysine peptide length and polymer molecular weight. Interestingly, 50% longer (K15) transfected very poorly compared optimized comprised K10 despite similar chemical composition...
One of the major intracellular barriers to nonviral gene delivery is efficient endosomal escape. The incorporation histidine residues into polymeric constructs has been found increase escape via proton sponge effect. Statistical and diblock copolymers N-(2-hydroxypropyl)methacrylamide (HPMA), oligolysine, oligohistidine were synthesized reversible-addition fragmentation chain transfer (RAFT) polymerization tested for in vitro transfection efficiency, buffering ability, polyplex uptake...
Acquisition of self-reactive effector CD4+ T cells is a major component the autoimmune response that can occur during myocarditis, an inflammatory form cardiomyopathy. Although processes by which gain function have received considerable attention, how these contribute to organ inflammation and damage less clear. Here, we identified IL-3–dependent amplification loop exacerbates inflammation. In experimental show organ–accumulating autoreactive IL-3+ stimulate IL-3R+ tissue macrophages produce...
Cocaine abuse is problematic, directly and indirectly impacting the lives of millions, yet existing therapies are inadequate usually ineffective. A cocaine vaccine would be a promising alternative therapeutic option, but efficacy hampered by variable production anticocaine antibodies. Thus, new tactics strategies for boosting immunogenicity must explored. Flagellin bacterial protein that stimulates innate immune response via binding to extracellular Toll-like receptor 5 (TLR5) also...
Quantitative analysis of the intracellular trafficking nonviral vectors provides critical information that can guide rational design improved cationic systems for gene delivery. Subcellular fractionation methods, combined with radiolabeling, produce quantitative measurements and therapeutic payload. In this work, differential density-gradient centrifugation techniques were used to determine distribution radiolabeled 25 kDa branched polyethylenimine (bPEI)/plasmid DNA complexes ("polyplexes")...
Mutations in the nucleotide oligomerization domain-2 (NOD2) gene and positive antibodies to microbial antigens have been found be associated with Crohn's disease (CD) phenotype, fibrostenosis. The aim of this study was confirm these relationships a large cohort CD patients determine correlation between presence NOD2 variants oligomannan, CBir, outer membrane porin-C (OmpC), I2 fibrostenosis.Sera DNA from 731 unrelated were tested for (SNP 8, 12, 13) antibodies. results correlated phenotypes,...
Polycations have been successfully used as gene transfer vehicles both in vitro and vivo; however, their cytotoxicity has associated with increasing molecular weight. Polymers that can be rapidly degraded after internalization are typically better tolerated by mammalian cells compared to non-degradable counterparts. Here, we report the use of a dibromomaleimide-alkyne (DBM-alkyne) linking agent reversibly bridge cationic polymer segments for delivery provide site-specific functionalization...