A5087308396- T-cell and B-cell Immunology
- Systemic Lupus Erythematosus Research
- Immune Cell Function and Interaction
- Immunotherapy and Immune Responses
- Receptor Mechanisms and Signaling
- Cytokine Signaling Pathways and Interactions
- Neuroscience and Neuropharmacology Research
- Monoclonal and Polyclonal Antibodies Research
- Neurotransmitter Receptor Influence on Behavior
- Immune Response and Inflammation
- Immunodeficiency and Autoimmune Disorders
- interferon and immune responses
- Diabetes and associated disorders
- Reproductive System and Pregnancy
- Tryptophan and brain disorders
- Nerve injury and regeneration
- S100 Proteins and Annexins
- Atherosclerosis and Cardiovascular Diseases
- Pancreatic function and diabetes
- Neurogenesis and neuroplasticity mechanisms
- Cellular transport and secretion
- RNA regulation and disease
- Microscopic Colitis
- Stress Responses and Cortisol
- Phagocytosis and Immune Regulation
Cleveland Clinic Lerner College of Medicine
2013-2025
Case Western Reserve University
2014-2025
University of Copenhagen
2010-2023
Cleveland Clinic
2010-2022
Sankt Hans Hospital
2018
Mental Health Services
2018
Lundbeck (Denmark)
2018
PharmacoGenetics (China)
2014
Lundbeck Foundation
2013
Cleveland State University
2012
The serotonin transporter (SERT) terminates neurotransmission by removing from the synaptic cleft. In addition, it is site of action antidepressants (which block transporter) and amphetamines induce substrate efflux). We explored functional importance N terminus in mediating focusing initially on highly conserved threonine residue at position 81, a candidate for phosphorylation protein kinase C. Molecular dynamics simulations wild type SERT, compared with its mutations SERT(T81A) SERT(T81D),...
Dopamine regulates reward, cognition, and locomotor functions. By mediating rapid reuptake of extracellular dopamine, the dopamine transporter is critical for spatiotemporal control dopaminergic neurotransmission. Here, we use super-resolution imaging to show that dynamically sequestrated into cholesterol-dependent nanodomains in plasma membrane presynaptic varicosities neuronal projections neurons. Stochastic optical reconstruction microscopy reveals irregular (∼70 nm mean diameter) were...
Abstract Objective To determine whether overexpression of BAFF can accelerate the development systemic lupus erythematosus–associated end‐organ disease in hosts with an underlying autoimmune diathesis. Methods We introduced a transgene (Tg) into autoimmune‐prone B6.Sle1 and B6.Nba2 mice evaluated these for serologic autoimmunity renal pathology. Results B6.Sle1.BAFF B6.Nba2.BAFF mice, but not non‐Tg littermates, frequently developed severe glomerular pathology by 3 months age. Age‐matched...
The dopamine transporter (DAT) mediates reuptake of released and is the target for psychostimulants, such as cocaine amphetamine. DAT undergoes marked constitutive endocytosis, but little known about fate sorting endocytosed transporter. To study in cells lines, we fused one-transmembrane segment protein Tac to DAT, thereby generating a (TacDAT) with an extracellular antibody epitope suited trafficking studies. TacDAT was functional constitutively HEK293 cells. According ELISA-based assay,...
Autoantibodies are of central importance in the pathogenesis Ab-mediated autoimmune disorders. The murine lupus susceptibility locus Nba2 on chromosome 1 and syntenic human associated with a loss immune tolerance that leads to antinuclear Ab production. To identify gene intervals within control development autoantibody-producing B cells determine cellular components through which genes accomplish this, we generated congenic mice expressing various where for FcgammaR, SLAM, IFN-inducible...
Objective Patients with systemic lupus erythematosus (SLE) often present elevated levels of interferon‐α (IFNα) in serum. Plasmacytoid dendritic cells (pDCs) have been suggested to be the primary source IFNα SLE due their capacity produce high IFNα. During viral infection, a subset pDCs expressing sialic acid–binding immunoglobulin‐type lectin H (Siglec H) produces majority pDC‐derived The aim this study was provide evidence that Siglec H–positive are pathogenic IFNα‐dependent B6.Nba2 mouse...
Abstract Although Act1 (adaptor for IL-17 receptors) is necessary IL-17-mediated inflammatory responses, - (but not Il17ra- , Il17rc- or Il17rb -) deficient mice develop spontaneous SLE- and Sjögren’s-like diseases. Here, we show that functions as a negative regulator in T B cells via direct inhibition of STAT3. Mass spectrometry analysis detected an Act1–STAT3 complex, deficiency Il17ra -, ) results hyper IL-23- IL-21-induced STAT3 activation cells, respectively. IL-23R deletion blockade...
CD40L and B lymphocyte-activating factor (BAFF), members of the TNF superfamily, play critical roles in cell survival activation, regulation humoral immunity. We previously reported that adaptor molecule Act1 functions as a negative regulator CD40- BAFF-mediated survival. Here we demonstrated mice deficient developed systemic autoimmune disease with histological serological features human Sjögren's syndrome (SS), association lupus erythematosus-like nephritis. Analyses Act1(-/-)CD40(-/-)...
Background: Vitamin D deficiency is a known risk factor for Systemic Lupus Erythematosus (SLE), yet clinical trials have not demonstrated efficacy and few studies utilized lupus models to understand the mechanism underlying this relationship. The Act1-/- mouse spontaneous model of Sjögren’s syndrome, characterized by increased Th17 cells peripheral B cell expansion. D3 has anti-inflammatory properties, reduces impairs differentiation/activation. Therefore, we assessed how varying amounts...
The life and death of T cells is controlled to a large extent by the relative amounts Bcl-2-related proteins they contain. antiapoptotic protein Bcl-2 proapoptotic Bim are particularly important in this process with amount per cell dropping about one-half when prepare die. In study we show that each control expression other. Absence leads drop intracellular protein, while having no effect on mRNA for Bcl-2. Conversely, high allow Bim, although case involves increases mRNA. These mutual...
The serotonin transporter (SERT) plays a critical role in regulating signaling by mediating reuptake of from the extracellular space. molecular and cellular mechanisms controlling SERT levels membrane remain poorly understood. To study trafficking surface resident SERT, two functional epitope-tagged variants were generated. Fusion FLAG-tagged one-transmembrane segment protein Tac to N terminus generated with an epitope suited for studies (TacSERT). Likewise, construct antibody was...
To investigate the role of Toll-like Receptor 7 (TLR7) in development neuropsychiatric lupus (NPSLE) B6.Nba2 murine model SLE. TLR7-deficient mice were evaluated for NPSLE symptoms through behavioral testing with comparison groups wild-type NPSLE-prone and B6 controls. Behavioral results context biomarker data, including flow cytometry immune cell activation, enzyme-linked immunosorbent assays (ELISA) to measure serum cytokine autoantibody levels, autoantibodies targeted against double...
Summary In order to avoid autoimmunity and excessive tissue destruction, the action of certain immunoinhibitory substances are very important for negative regulation immune system. Interleukin‐10 (IL‐10) is an immunoregulatory cytokine which thought negatively affect both T cells antigen‐presenting in vivo . Adoptive transfer IL‐10‐treated bone‐marrow‐derived dendritic (BMDCs) may be one therapeutic avenue inhibit autoimmunity. this study we present a comprehensive analysis effects IL‐10 on...
Systemic lupus erythematosus (SLE) is a prototype autoimmune disease. In human SLE patients, as well in mouse models of SLE, the development disease associated with increased levels pro-inflammatory cytokines, such interleukin-6 (IL-6). However, IL-6 target genes contributing to remain be identified. Our previous studies one model identified an interferon-inducible gene, Ifi202, major contributor We now report that induces expression Ifi202 gene. found treatment splenocytes mRNA and p202...