A5006801377- Neuroinflammation and Neurodegeneration Mechanisms
- Epigenetics and DNA Methylation
- Multiple Sclerosis Research Studies
- Amino Acid Enzymes and Metabolism
- Immune cells in cancer
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Metabolism and Genetic Disorders
- Mitochondrial Function and Pathology
- Immune Response and Inflammation
- Adenosine and Purinergic Signaling
- Endoplasmic Reticulum Stress and Disease
- Immune Cell Function and Interaction
- RNA Interference and Gene Delivery
- Neurogenesis and neuroplasticity mechanisms
- Molecular Biology Techniques and Applications
- Autophagy in Disease and Therapy
- Signaling Pathways in Disease
- Peripheral Neuropathies and Disorders
- Metabolomics and Mass Spectrometry Studies
- Cancer-related Molecular Pathways
- Ocular Diseases and Behçet’s Syndrome
- Cardiac Ischemia and Reperfusion
- Genetics, Aging, and Longevity in Model Organisms
- Dietary Effects on Health
- Tryptophan and brain disorders
Johns Hopkins Medicine
2008-2025
Johns Hopkins University
2010-2025
University of Baltimore
2022-2023
Johns Hopkins Hospital
2017-2021
Nationwide Children's Hospital
2021
Mayo Clinic
2021
National Institutes of Health
2021
American Academy of Neurology
2021
University of Miami
2021
University of Virginia Medical Center
2021
Immunometabolism as therapeutic target Dimethyl fumarate (DMF) is an immunomodulatory compound used to treat multiple sclerosis and psoriasis whose mechanisms of action remain only partially understood. Kornberg et al. found that DMF its metabolite, monomethyl fumarate, succinate the glycolytic enzyme GAPDH (see Perspective by Matsushita Pearce). After treatment, was inactivated, aerobic glycolysis down-regulated in both myeloid lymphoid cells. This resulted down-modulated immune responses...
BackgroundIntermittent fasting or calorie restriction (CR) diets provide anti-inflammatory and neuroprotective advantages in models of multiple sclerosis (MS); data humans are sparse.MethodsWe conducted a randomised-controlled feeding study different CR 36 people with MS over 8 weeks. Participants were randomised to 1 3 diets: 1) control diet, which the participant received 100% his her needs 7 days per week, 2) daily 78% 3) an intermittent on 5 week 25% 2 (i.e., "5:2" style diet)....
In multiple sclerosis (MS), microglia and macrophages within the central nervous system (CNS) play an important role in determining balance among demyelination, neurodegeneration, myelin repair. Phagocytic regenerative functions of these CNS innate immune cells support remyelination, whereas chronic maladaptive inflammatory activation promotes lesion expansion disability, particularly progressive forms MS. No currently approved drugs convincingly target CNS, contributing to lack therapies...
Significance d -amino acids are increasingly recognized as important signaling molecules in the mammalian central nervous system. Cysteine is amino acid with fastest vitro spontaneous racemization rate, but its -stereoisomer has not been examined. Here, we establish presence of endogenous -cysteine brain. Using sensitive and specific assays, delineate actions a negative regulator growth factor during cortical development identify putative binding partner mediating these effects. By...
The circulating metabolome provides unique insights into multiple sclerosis (MS) pathophysiology, but existing studies are relatively small or characterized limited metabolites. We test for differences in the between people with MS (PwMS; n = 637 samples) and healthy controls (HC; 317 assess association metabolomic profiles disability PwMS. then whether metabolic correlate changes cellular gene expression using publicly available scRNA-seq data identified metabolites affect human immune cell...
Significance Multiple sclerosis (MS) is an inflammatory disease that targets the central nervous system and leads to severe neurologic disability. Bryostatin-1 a naturally occurring, brain-penetrant compound has undergone human testing in cancer Alzheimer’s disease, but also immunomodulatory properties might provide benefit MS. Here, we show bryostatin-1 potently prevents reverses deficits major mouse model of MS, experimental autoimmune encephalomyelitis (EAE). Its even late-stage EAE...
The differentiation and suppressive functions of regulatory CD4 T cells (Tregs) are supported by a broad array metabolic changes, providing potential therapeutic targets for immune modulation. In this study, we focused on the role glycolytic enzymes in Tregs identified phosphoglycerate mutase (PGAM) as being differentially overexpressed associated with highly phenotype. Pharmacologic or genetic inhibition PGAM reduced Treg function while reciprocally inducing markers pro-inflammatory, helper...
The differentiation and suppressive functions of regulatory CD4 T cells (Tregs) are supported by a broad array metabolic changes, providing potential therapeutic targets for immune modulation. In this study, we focused on the role glycolytic enzymes in Tregs identified phosphoglycerate mutase (PGAM) as being differentially overexpressed associated with highly phenotype. Pharmacologic or genetic inhibition PGAM reduced Treg function while reciprocally inducing markers pro-inflammatory, helper...
Abstract Objective Identify metabolic changes produced by dimethyl fumarate ( DMF ) treatment and link them to immunological effects. Methods We enrolled 18 MS patients obtained blood prior 6 months postinitiation. also healthy controls for comparison. performed global metabolomics on plasma used weighted correlation network analysis WGCNA identify modules of correlated metabolites. identified that changed with treatment, followed targeted corroborate in analyses. metabolite individual...
The COVID-19 pandemic caused by the SARS-CoV-2 virus has left many unanswered questions for patients with neurological disorders and providers caring them. Elderly immunocompromised are at increased risk severe symptoms due to COVID-19, may increase of underlying illness, particularly those significant bulbar respiratory weakness or other neurologic disability. Emerging vaccines offer substantial protection from symptomatic infection, but both have concerns regarding theoretical risks...
Significance Inositol pyrophosphates are versatile messenger molecules containing the energetic pyrophosphate bond. One of principal enzymes generating inositol IP 7 (5-diphosphoinositolpentakisphosphate) is hexakisphosphate kinase 2 (IP6K2). Previous work has shown that IP6K2 neuroprotective and maintains mitochondrial respiration. We now report loss leads to increased fission mitophagy. Regulation dynamics by depends on protein PINK1 and, interestingly, independent enzymatic activity....
Significance Inositol hexakisphosphate kinase 2 (IP6K2) regulates various cellular processes. Here we establish a role for IP6K2 in the brain. deletion leads to impaired mitochondrial function and repression of cytochrome c1 subunit electron transport chain, complex III. also elicits decreased creatine kinase-B, ATP, phosphocreatine levels as well enhanced oxidative stress. Restoring ATP abrogates deficits mitigates neuronal death. These observations reveal unique homeostasis associated with...
ABSTRACT The circulating metabolome is a product of interactions between the genome, epigenome, exposome and microbiome. may be altered in people with multiple sclerosis (MS); however, existing metabolomics studies were relatively small or characterized limited number metabolites. Herein, we performed multi-site study profiling to obtain relative abundances for 269 metabolites large cohort MS patients healthy controls. After adjusting batch effects extensive quality control, created an...
Protein kinase C (PKC) plays a key role in modulating the activities of innate immune cells central nervous system (CNS). A delicate balance between pro-inflammatory and regenerative by microglia CNS-associated macrophages is necessary for proper functioning CNS. Thus, maladaptive activation these CNS results neurodegeneration demyelination associated with various neurologic disorders, such as multiple sclerosis (MS) Alzheimer’s disease. Prior studies have demonstrated that modulation PKC...
Racial/ethnic disparities have a significant impact on bladder cancer outcomes with African American patients demonstrating inferior survival over European-American patients. We hypothesized that epigenetic difference in methylation of tumor DNA is an underlying cause this health disparity. analyzed tumors from and using reduced representation bisulfite sequencing (RRBS) to annotate differentially methylated regions. Liquid chromatography-mass spectrometry (LC-MS/MS) based metabolomics flux...
Multiple sclerosis (MS) is a neuroinflammatory disease of the central nervous system (CNS). Although classically considered demyelinating disease, neuroaxonal injury occurs in both acute and chronic phases represents pathologic substrate disability not targeted by current therapies. Nitric oxide (NO) generated CNS macrophages microglia contributes to all MS, but candidate therapies that prevent NO-mediated have been identified. Here, we demonstrate multifunctional protein...