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One or more keywords matched the following properties of Domowicz, Miriam
keywords Extracellular Matrix, Proteoglycans, Pediatric Neurodegeneration, Perinatal brain injury, Neuroglia,
overview Our research aims to understand the function of proteoglycans during brain and cartilage development. In collaboration with Dr. Schwartz, we have studied several proteoglycan mutant models which indicate that the proteoglycan aggrecan plays a key role in establishing appropriate gradients of growth factors during cartilage development and that it is involved as instructive signaling that controls astrocyte differentiation during avian brain development. More recently, we have developed a novel embryonic model for brain injury in the avian which allows analysis of glial precursor response to injury and modifications of matrix biosynthesis. This work led us to develop a novel multifactorial model of perinatal injury in mice in which we demonstrated that perinatal brain injury followed by exposure to lipopolysaccharide (as an analog of remote pathogen exposure), particularly affects maturation markers in oligodendrocytes, initiates a neuroinflammatory process and activates a neural stem cell response. These models will aid in our understanding of complex human diseases such as periventricular leukomalacia and cerebral palsy. Another line of research aims to understand the involvement of astrocytes and microglia and the integrity of blood-CSF and the blood brain barrier in a mouse model of a Neuronal Ceroid Lipofuscinoses (NCLs, also known as Batten disease). NCLs are among the most common neurodegenerative diseases in the pediatric population, with an incidence estimated at 2-4 per 100,000 live births. Different forms of the diseases were originally classified based on the time of onset: infantile, late infantile (LINCL), juvenile and adult. Over 13 gene mutations have been found to be linked to NCLs. In particular, the classical late-infantile NCL (cLINCL) in humans is caused by mutations in the CLN2/TPP1 gene. The mouse model lacks expression of TPP1 and develops a lethal neurodegeneration in the first 5 month of life. We have addressed the evolution of the disease using RNAseq and have identified inflammation pathways in which microglia and astrocyte activation potentiate neuronal dysfunction, possibly by oxidative stress and damage of the blood–brain barrier integrity. Our long-term goal is to establish novel parameters for early disease detection which may lead to novel therapies.
One or more keywords matched the following items that are connected to Domowicz, Miriam
Item TypeName
Concept Proteoglycans
Concept Heparan Sulfate Proteoglycans
Concept Chondroitin Sulfate Proteoglycans
Academic Article S103L reactive chondroitin sulfate proteoglycan (aggrecan) mRNA expressed in developing chick brain and cartilage is encoded by a single gene.
Academic Article Age-dependent inhibition of neural crest migration by the notochord correlates with alterations in the S103L chondroitin sulfate proteoglycan.
Academic Article Viral and cellular requirements for entry of herpes simplex virus type 1 into primary neuronal cells.
Academic Article Domain organization, genomic structure, evolution, and regulation of expression of the aggrecan gene family.
Academic Article Role of the C-terminal G3 domain in sorting and secretion of aggrecan core protein and ubiquitin-mediated degradation of accumulated mutant precursors.
Academic Article Developmental expression of the HNK-1 carbohydrate epitope on aggrecan during chondrogenesis.
Academic Article Aggrecan regulates telencephalic neuronal aggregation in culture.
Academic Article NOVOcan: a molecular link among selected glial cells.
Academic Article Chondrodysplasias due to proteoglycan defects.
Academic Article APBP-1, a DNA/RNA-binding protein, interacts with the chick aggrecan regulatory region.
Academic Article Proteoglycans in brain development.
Academic Article The biochemically and immunologically distinct CSPG of notochord is a product of the aggrecan gene.
Academic Article Proteoglycans: gene cloning.
Academic Article Brain aggrecan.
Academic Article Cell specific-chondroitin sulfate proteoglycan expression during CNS morphogenesis in the chick embryo.
Academic Article Proteoglycans in brain development and pathogenesis.
Academic Article Vascular dimorphism ensured by regulated proteoglycan dynamics favors rapid umbilical artery closure at birth.
Academic Article Roles of Chondroitin Sulfate Proteoglycans as Regulators of Skeletal Development.
Academic Article Chemistry and Function of Glycosaminoglycans in the Nervous System.
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  • Proteoglycans