A5089540054- Virus-based gene therapy research
- Herpesvirus Infections and Treatments
- Cancer, Hypoxia, and Metabolism
- Eosinophilic Esophagitis
- Viral Infections and Immunology Research
- Eosinophilic Disorders and Syndromes
- Viral gastroenteritis research and epidemiology
- Protease and Inhibitor Mechanisms
- Cardiac electrophysiology and arrhythmias
- Virology and Viral Diseases
- Liver Disease Diagnosis and Treatment
- Viral Infections and Vectors
- interferon and immune responses
- Alcohol Consumption and Health Effects
- Cardiovascular Effects of Exercise
- Mosquito-borne diseases and control
- HIV Research and Treatment
- Respiratory viral infections research
- Muscle Physiology and Disorders
- Adipose Tissue and Metabolism
- PARP inhibition in cancer therapy
- Food Allergy and Anaphylaxis Research
- Mast cells and histamine
- Cardiomyopathy and Myosin Studies
- Nuclear Receptors and Signaling
Cornell University
2016-2024
Albert Einstein College of Medicine
2011-2016
University of Pennsylvania
2008-2010
Pathogenic variants in PKP2 (plakophilin-2) cause arrhythmogenic right ventricular cardiomyopathy, a disease characterized by life-threatening arrhythmias and progressive cardiomyopathy leading to heart failure. No effective medical therapy is available prevent or arrest the disease. We tested hypothesis that adeno-associated virus vector-mediated delivery of human
ABSTRACT Hantaviruses cause hemorrhagic fever with renal syndrome (HFRS) in the Old World and a highly fatal hantavirus cardiopulmonary (HCPS) New World. No vaccines or antiviral therapies are currently available to prevent treat disease, gaps our understanding of how hantaviruses enter cells challenge search for therapeutics. We performed haploid genetic screen human identify host factors required entry by Andes virus, virulent hantavirus. found that multiple genes involved cholesterol...
The enveloped alphaviruses include important and emerging human pathogens such as Chikungunya virus Eastern equine encephalitis virus. Alphaviruses enter cells by clathrin-mediated endocytosis, exit budding from the plasma membrane. While there has been considerable progress in defining structure function of viral proteins, relatively little is known about host factors involved alphavirus infection. We used a genome-wide siRNA screen to identify that promote or inhibit infection cells. Fuzzy...
ABSTRACT To initiate membrane fusion and virus entry, herpes simplex (HSV) gD binds to a cellular receptor such as herpesvirus entry mediator (HVEM). HVEM is tumor necrosis factor (TNF) family member with four natural ligands that either stimulate (LIGHT LTα) or inhibit (BTLA CD160) T cell function. We hypothesized the interaction of affects binding ligands, thereby modulating immune response during infection. Here, we investigated effect has on its ligands. First, HSV virions cells...
Friedreich's ataxia (FA), an autosomal recessive disorder caused by a deficiency in the expression of frataxin (FXN), is characterized progressive and hypertrophic cardiomyopathy. Although cardiac dysfunction most common cause mortality FA, disease remains subclinical for clinical course because neurologic limits muscle oxygen demands. Previous FXN knockout mouse models exhibit fatal cardiomyopathy similar to human but contrast condition, untreated mice become moribund 2 months age, unlike...
Aldehyde dehydrogenase 2 (ALDH2) deficiency causes "Asian flush syndrome," presenting as alcohol-induced facial flushing, tachycardia, nausea, and headaches. One of the most common hereditary enzyme deficiencies, it affects 35%–40% East Asians 8% world population. ALDH2 is key in ethanol metabolism; with challenge, ALDH2*2 (E487K) mutation results accumulation toxic acetaldehyde. heterozygotes have increased risk for upper digestive tract cancers, compounded by smoking drinking alcohol. We...
ABSTRACT Background Pathogenic variants in plakophilin-2 (PKP2) cause arrhythmogenic right ventricular cardiomyopathy (ARVC), a disease characterized by life-threatening arrhythmias and progressive leading to heart failure. No effective medical therapy is available prevent and/or arrest the disease. We tested hypothesis that AAV-mediated delivery of human PKP2 gene an adult mammalian deficient can progression significantly prolong survival. Methods Experiments were carried out using...
Alphaviruses are small enveloped RNA viruses that infect cells via clathrin-mediated endocytosis and low-pH-triggered fusion in the early endosome. Using a interfering (siRNA) screen human cells, we previously identified TSPAN9 as host factor promotes infection by alphaviruses Sindbis virus (SINV), Semliki Forest (SFV), chikungunya (CHIKV). Depletion of specifically decreases SFV membrane endosomes. is member tetraspanin family multipass proteins, but its cellular function currently unknown....
Homologous recombination (HR) is a mechanism for repairing DNA interstrand crosslinks and double-strand breaks. In mammals, HR requires the activities of RAD51 family (RAD51, RAD51B, RAD51C, RAD51D, XRCC2, XRCC3 DMC1), each which contains conserved ATP binding sequences (Walker Motifs A B). RAD51D DNA-stimulated ATPase that interacts directly with RAD51C XRCC2. To test hypothesis hydrolysis by are required repair crosslinks, site-directed mutations in Walker Motif were generated,...
Chronic traumatic encephalopathy (CTE) is a progressive neurodegenerative disorder caused by repetitive trauma to the central nervous system (CNS) suffered soldiers, contact sport athletes, and civilians following accident-related trauma. CTE CNS tauopathy, with trauma-induced inflammation leading accumulation of hyperphosphorylated forms microtubule-binding protein Tau (pTau), resulting in neurofibrillary tangles loss neurons. At present, there are no therapies treat CTE. We hypothesized...
Alpha-1 antitrypsin deficiency (AATD) manifests primarily as early-onset emphysema caused by the destruction of lung neutrophil elastase due to low amounts serine protease inhibitor alpha-1 (AAT). The current therapy involves weekly intravenous infusions AAT-derived from pooled human plasma that is efficacious, yet costly. Gene applications designed provide constant levels AAT protein are currently under development. challenge for gene sufficient normalize level and anti-neutrophil capacity...
Alpha 1-antitrypsin (AAT) deficiency, a hereditary disorder characterized by low serum levels of functional AAT, is associated with early development panacinar emphysema. AAT inhibits serine proteases, including neutrophil elastase, protecting the lung from proteolytic destruction. Cigarette smoke, pollution, and inflammatory cell-mediated oxidation methionine (M) 351 358 inactivates limiting protection. In vitro studies using amino acid substitutions demonstrated that replacing M351 valine...
Eosinophils are specialized granulocytic effector cells that store and release highly active mediators used in immune defense. also implicated the pathogenesis of allergic disorders, including eosinophilic esophagitis (EoE), a chronic disorder characterized by infiltration eosinophils into esophagus damage tissue, resulting gastrointestinal morbidity, food impaction, dysphagia. Treatment with elimination diets and/or topical corticosteroid therapy slow disease progression, but complicated...
Aldehyde dehydrogenase type 2 (ALDH2), a key enzyme in ethanol metabolism, processes toxic acetaldehyde to nontoxic acetate. ALDH2 deficiency affects 8% of the world population and 35–45% East Asians. The ALDH2*2 allele common genetic variant has glutamic acid-to-lysine substitution at position 487 (E487K) that reduces oxidizing ability resulting systemic accumulation with ingestion. With chronic ingestion, mutations are associated variety hematological, neurological, dermatological...
Intravenous (IV) administration of naturally occurring adeno-associated virus (AAV) vectors are liver tropic, with a significant proportion the total vector dose mediating gene expression in hepatocytes. AAV capsids that directed toward other organs such as lung may be useful for therapy nonliver-based diseases. Based on knowledge capillary endothelium is first bed encountered by an intravenously administered vector, and glycocalyx enriched negatively charged sialic acid, we hypothesized...
The homozygous Apolipoprotein E (APOE4) genotype is the major risk factor for development of early Alzheimer's disease. Genome engineering studies in mouse models human APOE4-dependent pathology have established that reduction APOE4 expression can rescue phenotype. We hypothesized could be suppressed CNS homozygotes using adeno-associated virus (AAV) microRNAs (miRNA) designed to hybridize APOE mRNA. screened nine different miRNAs targeting following transfection HEK293T and Huh7 cells....
Chronic hypereosinophilia, defined as persistent elevated blood levels of eosinophils ≥1,500/μL, is associated with tissue infiltration and consequent organ damage by eosinophil release toxic mediators. The current therapies for chronic hypereosinophilia have limited success, require repetitive administration, are a variety adverse effects. As novel approach to treat we hypothesized that adeno-associated virus (AAV)-mediated delivery an anti-human antibody would provide one-time therapy...
They may love the idea of a cute fluffy addition to their household, but how ready are they for pet rabbit? Pet charity Blue Cross reveals why rabbits one most misunderstood pets
Aldehyde dehydrogenase 2 (ALDH2) deficiency affects 35% to 45% of East Asians and 8% the world population. ALDH2 is second enzyme in ethanol metabolism pathway. The common genetic variant