A5102956688- Neurogenesis and neuroplasticity mechanisms
- Mesenchymal stem cell research
- Neuroinflammation and Neurodegeneration Mechanisms
- Multiple Sclerosis Research Studies
- Pluripotent Stem Cells Research
- Lysosomal Storage Disorders Research
- Immune cells in cancer
- RNA Interference and Gene Delivery
- Neonatal and fetal brain pathology
- Spinal Dysraphism and Malformations
- CAR-T cell therapy research
- Glycogen Storage Diseases and Myoclonus
- Pancreatic function and diabetes
- Metabolism and Genetic Disorders
- Anesthesia and Neurotoxicity Research
- Barrier Structure and Function Studies
- Erythrocyte Function and Pathophysiology
- Sphingolipid Metabolism and Signaling
- Alzheimer's disease research and treatments
- Neurological Disease Mechanisms and Treatments
- Nerve injury and regeneration
- Phagocytosis and Immune Regulation
- Spinal Cord Injury Research
- Neurological diseases and metabolism
- Receptor Mechanisms and Signaling
University of Oxford
2024
Marcus (United States)
2019-2024
Duke University
2012-2024
Eunice Kennedy Shriver National Institute of Child Health and Human Development
2007-2020
Duke Medical Center
2014-2019
Duke University Hospital
2017-2019
National Institutes of Health
2007-2012
Disruption of the blood-brain barrier (BBB) is a serious complication frequently encountered in neurodegenerative disorders.Infantile neuronal ceroid lipofuscinosis (INCL) devastating childhood lysosomal storage disorder caused by palmitoyl-protein thioesterase-1 (PPT1) deficiency.It remains unclear whether BBB disrupted INCL and if so, what might be molecular mechanism(s) this complication.We previously reported that Ppt1-knockout (Ppt1-KO) mice mimic manifest high levels oxidative stress...
In the majority of neurodegenerative storage disorders, neuronal death in brain is followed by infiltration phagocytic cells (e.g. activated microglia, astroglia and macrophages) for efficient removal cell corpses. However, it increasingly evident that these phagocytes may also cause adjoining viable neurons contributing to rapid progression neurodegeneration. Infantile ceroid lipofuscinosis (INCL) a devastating, neurodegenerative, lysosomal disorder caused inactivating mutations...
Microglia and monocytes play important roles in regulating brain remyelination. We developed DUOC-01, a cell therapy product intended for treatment of demyelinating diseases, from banked human umbilical cord blood (CB) mononuclear cells. Immunodepletion selection studies demonstrated that DUOC-01 cells are derived CB CD14+ monocytes. compared the ability freshly isolated to accelerate remyelination brains NOD/SCID/IL2Rγnull mice following cuprizone feeding-mediated demyelination. The corpus...
Cord blood (CB) mononuclear cells (MNC) are being tested in clinical trials to treat hypoxic-ischemic (HI) brain injuries. Although early results encouraging, mechanisms underlying potential benefits not well understood. To explore these further, we exposed mouse organotypic slice cultures oxygen and glucose deprivation (OGD) then treated the slices with from CB or adult peripheral (PB). We found that CB-MNCs protect neurons OGD-induced death reduced both microglial astrocyte activation....
Abstract Introduction The central nervous system (CNS) has a specialized barrier, the blood brain barrier (BBB), that tightly regulates entry of circulating cells and molecules. BBB is compromised in many neurodegenerative diseases, thus understanding dysfunction critical to treating like multiple sclerosis (MS). CNS macrophages regulate have potential for development as cell therapy. Objectives In this study, we tested if umbilical cord derived (DUOC-01) could prevent suppress progression...
Serotonin plays a prominent role in neurodevelopment, regulating processes from cell division to synaptic connectivity. Clinical studies suggest that alterations serotonin signalling such as genetic polymorphisms or antidepressant exposure during pregnancy are risk factors for neurodevelopmental disorders. However, an understanding of how dysfunctional neuromodulation alters systems level activity over neocortical development is lacking. Here, we use longitudinal imaging approach investigate...
We developed a cell therapy product, DUOC-01, derived from banked human umbilical cord blood, to treat demyelinating conditions in the central nervous system.Previously, we demonstrated that DUOC-01 increased myelination and decreased gliosis cellular infiltration corpus callosum of immune-incompetent mice treated with cuprizone.To investigate mechanism test whether will be efficacious other models demyelination, tested lysophosphatidylcholine (LPC) demyelinated murine organotypic cerebellar...
Abstract Cord blood (CB) mononuclear cells (MNC) are being tested in clinical trials to treat hypoxic-ischemic (HI) brain injuries. Although early results encouraging, mechanisms underlying potential benefits not well understood. To explore these further, we exposed mouse organotypic slice cultures oxygen and glucose deprivation (OGD) then treated the slices with from CB or adult peripheral (PB). We found that CB-MNCs protect neurons OGD-induced death reduced both microglial astrocyte...
Abstract Introduction DUOC-01 is a macrophage-like cell therapy product manufactured by culturing banked human umbilical cord blood cells under GMP conditions. Currently, the safety of being tested as bridging in children with demyelinating leukodystrophies undergoing unrelated donor transplantation after myeloablative conditioning. protects against loss function several preclinical models conditions central nervous system, making it an attractive for patients multiple sclerosis (MS) who...
Background: Unrelated donor umbilical cord blood transplantation (UCBT) is an established therapy for treatment of children with certain inherited metabolic diseases (IMDs), in whom it improves function and extends life. However, takes a few months sufficient numbers cells to engraft the brain following CBT. During this time, patients often experience progressive loss neurologic are left residual irreversible impairment. We previously described engraftment after UCBT developed DUOC-01,...