A5034859462- Multiple Sclerosis Research Studies
- Immunotherapy and Immune Responses
- Cytokine Signaling Pathways and Interactions
- T-cell and B-cell Immunology
- Psoriasis: Treatment and Pathogenesis
- Systemic Lupus Erythematosus Research
- Immune Response and Inflammation
- Monoclonal and Polyclonal Antibodies Research
- interferon and immune responses
- Peripheral Neuropathies and Disorders
- Neuroinflammation and Neurodegeneration Mechanisms
- Inflammasome and immune disorders
- vaccines and immunoinformatics approaches
- Immune Cell Function and Interaction
- NF-κB Signaling Pathways
- RNA regulation and disease
- Ultrasound and Hyperthermia Applications
- Mycobacterium research and diagnosis
- Chemokine receptors and signaling
- Immunodeficiency and Autoimmune Disorders
- RNA Research and Splicing
- HIV Research and Treatment
- HIV-related health complications and treatments
- Neurogenesis and neuroplasticity mechanisms
- Virus-based gene therapy research
Thomas Jefferson University
2019-2024
University of North Carolina at Chapel Hill
2012-2022
University at Buffalo, State University of New York
2015
Ono Pharmaceutical (United States)
2015
Bipar
2010
Indiana University School of Medicine
2010
Yale University
2006
National Institute of Neurological Disorders and Stroke
2000-2005
National Institutes of Health
2000-2005
National Cancer Institute
2004
Equal numbers of CD4+ T cells recognizing myelin basic protein (MBP) and proteolipid (PLP) are found in the circulation normal individuals multiple sclerosis (MS) patients. We hypothesized that if myelin-reactive critical for pathogenesis MS, they would exist a different state activation as compared with cloned from blood individuals. This was investigated total 62 subjects definitive MS. While there were no differences frequencies MBP- PLP-reactive after primary antigen stimulation,...
The objective of this study is to examine IL-11-induced mechanisms inflammatory cell migration the central nervous system (CNS). We report that IL-11 produced at highest frequency by myeloid cells among peripheral blood mononuclear (PBMC) subsets. Patients with relapsing–remitting multiple sclerosis (RRMS) have an increased + monocytes, and IL-11R CD4 lymphocytes, neutrophils in comparison matched healthy controls. granulocyte-macrophage colony-stimulating factor (GM-CSF) accumulate...
Identifying effective treatment combinations for MS patients failing standard therapy is an important goal. We report the results of a phase II open label baseline-to-treatment trial humanized monoclonal antibody against CD25 (daclizumab) in 10 multiple sclerosis with incomplete response to IFN-beta and high brain inflammatory clinical disease activity. Daclizumab was very well tolerated led 78% reduction new contrast-enhancing lesions significant improvement several outcome measures.
IFN-beta-1a has been used over the past 15 years as a primary therapy for relapsing-remitting multiple sclerosis (MS). However, immunomodulatory mechanisms that provide therapeutic effect against this CNS inflammatory disease are not yet completely elucidated. The of on Th17 cells, which play critical role in development autoimmune response, extensively studied humans. We have investigated dendritic cells (DCs) and naive CD4(+)CD45RA(+) T derived from untreated MS patients healthy controls...
Multiple lines of evidence suggest that CD4+ lymphocytes initiate autoimmune responses against myelin antigens in multiple sclerosis (MS). The increased frequency activated myelin-specific cells MS patients indicates the activation autoreactive represents a central event pathogenesis disease. We identified subpopulation is characterized phenotypically by persistent absence surface CD28 expression and functionally CD28-independent Th1 cytokine secretion. Owing to their...
Multiple lines of evidence suggest that CD4+ lymphocytes initiate autoimmune responses against myelin antigens in multiple sclerosis (MS). The increased frequency activated myelin-specific cells MS patients indicates the activation autoreactive represents a central event pathogenesis disease. We identified subpopulation is characterized phenotypically by persistent absence surface CD28 expression and functionally CD28-independent Th1 cytokine secretion. Owing to their...
Statins, extensively used as cholesterol-lowering agents, have recently been identified immunomodulatory agents. This study investigated the statins' mechanisms that target autoimmune response in humans, and evaluated their therapeutic potential multiple sclerosis. Our results demonstrated statin-mediated increases suppressor of cytokine secretion (SOCS) 3 7, which negatively regulate STAT/JAK signal transduction pathway IL-6 IL-23 gene expression monocytes. Simvastatin also induced...
Abstract Alemtuzumab (anti-CD52 mAb) provides long-lasting disease activity suppression in relapsing–remitting multiple sclerosis (RRMS). The objective of this study was to characterize the immunological reconstitution T cell subsets and its contribution prolonged RRMS following alemtuzumab-induced lymphocyte depletion. performed on blood samples from patients enrolled CARE-MS II clinical trial, which recently completed led submission alemtuzumab for U.S. Food Drug Administration approval as...
This paper describes the setup of a segmentation competition for automatic extraction Multiple Sclerosis (MS) lesions from brain Magnetic Resonance Imaging (MRI) data. is one three competitions that make up comparison workshop at 2008 Medical Image Computing and Computer Assisted Intervention (MICCAI) conference was modeled after successful on liver caudate 2007 MICCAI conference. In this paper, rationale organizing discussed, training test data sets both tasks are described scoring system...
IFN-beta, an effective therapy against relapsing-remitting multiple sclerosis, is naturally secreted during the innate immune response viral pathogens. The objective of this study was to characterize immunomodulatory mechanisms IFN-beta targeting and their effects on dendritic cell (DC)-mediated regulation T differentiation. We found that IFN-beta1a in vitro treatment human monocyte-derived DCs induced expression TLR7 members its downstream signaling pathway, including MyD88,...
Purpose.: AAV vectors produce stable transgene expression and elicit low immune response in many tissues. AAVs have been the of choice for gene therapy eye, particular retina. scAAVs are modified that bypass required second-strand DNA synthesis to achieve transcription transgene. The goal was investigate ability induce long-term, safe delivery transgenes trabecular meshwork living animals. Methods.: Single doses AAV2.GFP AAV2.RGD.GFP/Ad5.LacZ were injected intracamerally (IC) into rats (n =...
Although it is inarguable that conventional MRI (cMRI) has greatly contributed to the diagnosis and assessment of multiple sclerosis (MS), cMRI does not show close correlation with clinical findings or pathologic features, unable predict prognosis stratify disease severity. To this end, diffusion tensor imaging (DTI) tractography neuroconnectivity analysis may assist in MS. We, therefore, attempted pilot study for initial early relapsing‐remitting MS (RRMS). Neuroconnectivity was used...
IFN-β-1b is a first-line immunomodulatory therapy for relapsing-remitting multiple sclerosis (RR MS). However, its effects on B cells have not been characterized. In vitro studies of derived from RR MS patients revealed that decreases cells' stimulatory capacity, as detected by inhibition the Ag-specific T cell proliferative response upon Ag presentation IFN-β-1b-treated cells. Our study has identified inhibited capacity in and healthy controls through suppression CD40 CD80 expression,...
Abstract Objective: Neuromyelitis optica (NMO) and multiple sclerosis (MS) are considered inflammatory demyelinating diseases with distinguishing pathological characteristics. NMO pathology shows perivascular immunoglobulin G complement deposition, as well an astrocytopathy aquaporin‐4 (AQP4) loss. MS lesions reveal a profound, interindividual heterogeneity in immunopathological patterns of active demyelination, which has been challenged by the description stage‐dependent sequences features....
We investigated the immune response to proteolipid protein (PLP), most abundant central nervous system myelin in humans. A total of 8207 short-term T cell lines were generated from 49 individuals, 39 patients with multiple sclerosis and 10 control subjects. As we have reported previously, frequency PLP-reactive cells did not differ between two groups. To determine immunodominant PLP epitopes, proliferative responses 971 PLP-specific tested 27 overlapping 20-amino acid peptides encompassing...
Abstract Subsequent to the clinical trial of simvastatin in patients with relapsing remitting multiple sclerosis (RR MS), which demonstrated ability inhibit new inflammatory CNS lesion formation, current vitro study has characterized mechanisms through inhibits Th17 cell differentiation. The anti-inflammatory effects statins are mediated by inhibition isoprenylation, ensures proper membrane insertion and function proteins. Small GTPases, involved signal transduction pathways, key targets for...
Abstract Clinically isolated syndrome (CIS) suggestive of multiple sclerosis (MS) is the earliest clinically evident phase disease, which may provide valuable insight into molecular mechanisms initiation autoimmune response in MS. Our results introduce IL-11 as a new cytokine that plays role early disease. highest upregulated sera and cerebrospinal fluid from CIS patients, also increased patients with definitive relapsing-remitting MS comparison healthy control subjects. Serum levels are...
IL-11+CD4+ cells accumulate in the cerebrospinal fluid of patients with early relapsing-remitting multiple sclerosis (MS) and active brain MS lesions. Mouse studies have confirmed a causal role IL-11 exacerbation experimental autoimmune encephalomyelitis (RREAE). Administration at time clinical onset RREAE induced an acute increased scores, which persisted during entire course disease. numbers spinal cord inflammatory foci, as well peripheral CNS-infiltrating IL-17+CD4+ IL-17A serum levels....
Abstract The interaction of TCRs with MHC peptide ligands can be highly flexible, so that many different peptides are recognized by the same TCR in context a single restriction element. We provide quantitative description such interactions, which allows identification T cell epitopes and molecular mimics. response clones to positional scanning synthetic combinatorial libraries is analyzed mathematical approach based on model independent contribution individual amino acids Ag recognition....