A5039418200- Nerve injury and regeneration
- Neurogenesis and neuroplasticity mechanisms
- Spinal Cord Injury Research
- Gene expression and cancer classification
- Axon Guidance and Neuronal Signaling
- Neuroinflammation and Neurodegeneration Mechanisms
- Extracellular vesicles in disease
- Single-cell and spatial transcriptomics
- Immune cells in cancer
- Nerve Injury and Rehabilitation
- Bioinformatics and Genomic Networks
- MicroRNA in disease regulation
- Gene Regulatory Network Analysis
- Spinal Dysraphism and Malformations
- Virus-based gene therapy research
- Molecular Biology Techniques and Applications
- Cell Image Analysis Techniques
- Protein Degradation and Inhibitors
- Cancer Genomics and Diagnostics
- Histone Deacetylase Inhibitors Research
- Colorectal Cancer Treatments and Studies
- Graphene and Nanomaterials Applications
- Multiple Myeloma Research and Treatments
- Signaling Pathways in Disease
- Cholangiocarcinoma and Gallbladder Cancer Studies
University of Miami
2015-2024
Neurological Surgery
2015-2024
Foundation Medicine (United States)
2023
Bristol-Myers Squibb (United States)
2023
University of Central Florida
2022
University of Virginia
2001-2019
Moffitt Cancer Center
2015-2016
University of California, San Diego
2006-2015
University of California San Diego Medical Center
2005
United States Department of Veterans Affairs
2005
Injury to the CNS leads formation of scar tissue, which is important in sealing lesion and inhibiting axon regeneration. The fibrotic that comprises a dense extracellular matrix thought originate from meningeal cells surrounding CNS. However, using transgenic mice, we demonstrate perivascular collagen1α1 are main source cellular composition after contusive spinal cord injury dura remains intact. Using genetic lineage tracing, light sheet fluorescent microscopy, antigenic profiling, identify...
Axon regeneration in the central nervous system normally fails, part because of a developmental decline intrinsic ability CNS projection neurons to extend axons. Members KLF family transcription factors regulate regenerative potential developing neurons. Expression one member, KLF7, is down-regulated developmentally, and overexpression KLF7 cortical vitro promotes axonal growth. To circumvent difficulties achieving high neuronal expression exogenous we created chimera with VP16...
Abstract The cystic cavity that develops following injuries to brain or spinal cord is a major obstacle for tissue repair in central nervous system (CNS). Here we report injection of imidazole-poly(organophosphazenes) (I-5), hydrogel with thermosensitive sol–gel transition behavior, almost completely eliminates cavities clinically relevant rat injury model. Cystic are bridged by fibronectin-rich extracellular matrix. fibrotic matrix remodeling mediated metalloproteinase-9 expressed...
The wound healing process that occurs after spinal cord injury is critical for maintaining tissue homeostasis and limiting damage, but eventually results in a scar-like environment not conducive to regeneration repair. A better understanding of this dichotomy developing effective therapeutics target the appropriate pathobiology, major challenge has been large cellular heterogeneity immensely complex interactions. In study, we used single-cell RNA sequencing assess virtually all cell types...
Although infiltrating macrophages influence many pathological processes after spinal cord injury (SCI), the intrinsic molecular mechanisms that regulate their function are poorly understood. A major hurdle has been dissecting macrophage-specific functions from those in other cell types as well understanding how change over time. Therefore, we used RiboTag method to obtain mRNA directly injured mice and performed RNA sequencing investigate transcriptional profile. Our data show at 7 d SCI,...
After spinal cord injury (SCI), a fibrotic scar forms at the site that is best characterized by accumulation of perivascular fibroblasts and deposition extracellular matrix protein fibronectin. While fibronectin growth-permissive substrate for axons, inhibitory to axon regeneration. The mechanism behind how contributes environment assembled in unknown. By deleting myeloid cells, we demonstrate are most likely major source scar. In addition, initially present soluble form into 7 d post-SCI....
Changes in the molecular and cellular composition of CNS after injury or disease result formation an inhibitory environment that inhibits regeneration adult mammalian neurons. Although a dramatic change traumatic is hemorrhage because vascular rupture leakage blood-brain barrier, potential role for blood proteins repair processes remains unknown. Here we show protein fibrinogen inhibitor neurite outgrowth massively deposited spinal cord injury. We acts as ligand beta3 integrin induces...
Central nervous system (CNS) injuries are often debilitating, and most currently have no cure. This is due to the formation of a neuroinhibitory microenvironment at injury sites, which includes neuroinflammatory signaling non-permissive extracellular matrix (ECM) components. To address this challenge, viscous interfacial self-assembly approach, generate bioinspired hybrid 3D porous nanoscaffold platform for delivering anti-inflammatory molecules establish favorable 3D-ECM environment...
After CNS injuries, axon growth inhibitors from the myelin and scar tissue at injury site are considered major impediments to regeneration. The presence of several classes with multiple members in each class suggests functional redundancy inhibition. To test within inhibitory pathway, we analyzed raphe spinal serotonergic (5-HT) regeneration mice deficient two inhibitors, Nogo MAG, their common receptor NgR1 (or NgR). a complete transection cord injury, there was no significant enhancement...
The histological assessment of spinal cord tissue in three dimensions has previously been very time consuming and prone to errors interpretation. Advances clearing have significantly improved visualization fluorescently labelled axons. While recent proof-of-concept studies performed with transgenic mice which axons were prelabeled GFP, investigating axonal regeneration requires stringent tracing methods as well the use animal models labeling is not available. Using rodent injury, we labeled...
Mammalian target of rapamycin (mTOR) functions as a master sensor nutrients and energy, controls protein translation cell growth. Deletion phosphatase tensin homolog (PTEN) in adult CNS neurons promotes regeneration injured axons an mTOR-dependent manner. However, others have demonstrated mTOR-independent axon different types, raising the question how broadly mTOR regulates axonal regrowth across systems. Here we define role promoting collateral sprouting spared axons, key remodeling...
Abstract Astrocytes are a morphologically and functionally heterogeneous population of cells that play critical roles in neurodevelopment the regulation central nervous system homeostasis. Studies human astrocytes have been hampered by lack specific molecular markers difficulties associated with purifying culturing from adult brains. Human neural progenitor (NPCs) self‐renewal multipotent properties represent an appealing model to gain insight into developmental genetics function astrocytes,...