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Miriam Domowicz

TitleResearch Associate Professor
InstitutionUniversity of Chicago
DepartmentPediatrics-Kennedy Center
AddressChicago IL 60637
Phone+1 (773) 702-3780
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    Collapse Overview 
    Collapse 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.

    Collapse Biography 
    Collapse education and training
    Universidad Nacional de Córdoba, ArgentinaBS1983Biological Chemistry
    Universidad Nacional de Córdoba, ArgentinaPhD1989Neurochemistry
    Collapse awards and honors
    2015 - 2017Elected Treasurer, Chicago Chapter Society for Neuroscience
    2008 - 2010Elected Secretary, Chicago Chapter Society for Neuroscience
    2014Alan Berman Research Publication Award , Naval Research Laboratory
    1989 - 1990Postdoctoral Fellowship, Consejo Nacional de Investigaciones Científicas y Técnicas, Argentina
    1984 - 1988Fellowship, Consejo Nacional de Investigaciones Científicas y Técnicas, Argentina
    1983“Premio Universidad” First Mention, Universidad Nacional de Cordoba, Argentina

    Collapse Research 
    Collapse research activities and funding
    R03HD044677     (DOMOWICZ, MIRIAM)Jul 1, 2003 - Jun 30, 2006
    NIH
    Fate of Aggrecan-Expressing Progenitors in Gliogenesis
    Role: Principal Investigator

    Collapse Bibliographic 
    Collapse selected publications
    Publications listed below are automatically derived from MEDLINE/PubMed and other sources, which might result in incorrect or missing publications. Faculty can login to make corrections and additions.
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    PMC Citations indicate the number of times the publication was cited by articles in PubMed Central, and the Altmetric score represents citations in news articles and social media. (Note that publications are often cited in additional ways that are not shown here.) Fields are based on how the National Library of Medicine (NLM) classifies the publication's journal and might not represent the specific topic of the publication. Translation tags are based on the publication type and the MeSH terms NLM assigns to the publication. Some publications (especially newer ones and publications not in PubMed) might not yet be assigned Field or Translation tags.) Click a Field or Translation tag to filter the publications.
    1. Schwartz NB, Domowicz MS. Chemistry and Function of Glycosaminoglycans in the Nervous System. Adv Neurobiol. 2023; 29:117-162. PMID: 36255674.
      Citations: 2     Fields:    Translation:Humans
    2. Schwartz NB, Domowicz MS. Roles of Chondroitin Sulfate Proteoglycans as Regulators of Skeletal Development. Front Cell Dev Biol. 2022; 10:745372. PMID: 35465334; PMCID: PMC9026158.
      Citations: 1     
    3. Domowicz MS, Chan WC, Gonzalez T, Schwartz NB, Claudio-Vázquez P. Brain transcriptome analysis of a CLN2 mouse model as a function of disease progression. J Neuroinflammation. 2021 Nov 08; 18(1):262. PMID: 34749772; PMCID: PMC8576919.
      Citations: 4     Fields:    Translation:AnimalsCells
    4. Heller GJ, Marshall MS, Issa Y, Marshall JN, Nguyen D, Rue E, Pathmasiri KC, Domowicz MS, van Breemen RB, Tai LM, Cologna SM, Crocker SJ, Givogri MI, Sands MS, Bongarzone ER. Waning efficacy in a long-term AAV-mediated gene therapy study in the murine model of Krabbe disease. Mol Ther. 2021 05 05; 29(5):1883-1902. PMID: 33508430; PMCID: PMC8116612.
      Citations: 11     Fields:    Translation:AnimalsCells
    5. Nandadasa S, Szafron JM, Pathak V, Murtada SI, Kraft CM, O'Donnell A, Norvik C, Hughes C, Caterson B, Domowicz MS, Schwartz NB, Tran-Lundmark K, Veigl M, Sedwick D, Philipson EH, Humphrey JD, Apte SS. Vascular dimorphism ensured by regulated proteoglycan dynamics favors rapid umbilical artery closure at birth. Elife. 2020 09 10; 9. PMID: 32909945; PMCID: PMC7529456.
      Citations: 10     Fields:    Translation:HumansAnimalsCells
    6. Schwartz NB, Risner LE, Domowicz M, Freedman VH. Comparisons and Approaches of PREP Programs at Different Stages of Maturity: Challenges, Best Practices and Benefits. Ethn Dis. 2020; 30(1):55-64. PMID: 31969784; PMCID: PMC6970524.
      Citations: 1     Fields:    Translation:Humans
    7. Jo SY, Domowicz MS, Henry JG, Schwartz NB. The Role of Dot1l in Prenatal and Postnatal Murine Chondrocytes and Trabecular Bone. JBMR Plus. 2020 Feb; 4(2):e10254. PMID: 32083237; PMCID: PMC7017886.
      Citations: 8     
    8. Domowicz MS, Chan WC, Henry JG, Ware CB, Andrade J, Dawson G, Schwartz NB, Claudio-Vázquez P. Global Brain Transcriptome Analysis of a Tpp1 Neuronal Ceroid Lipofuscinoses Mouse Model. ASN Neuro. 2019 Jan-Dec; 11:1759091419843393. PMID: 31003587; PMCID: PMC6475859.
      Citations: 9     Fields:    Translation:AnimalsCells
    9. Schwartz NB, Domowicz MS. Proteoglycans in brain development and pathogenesis. FEBS Lett. 2018 12; 592(23):3791-3805. PMID: 29513405.
      Citations: 39     Fields:    Translation:HumansAnimals
    10. Domowicz M, Wadlington NL, Henry JG, Diaz K, Munoz MJ, Schwartz NB. Glial cell responses in a murine multifactorial perinatal brain injury model. Brain Res. 2018 02 15; 1681:52-63. PMID: 29274879; PMCID: PMC5780221.
      Citations: 6     Fields:    Translation:AnimalsCells
    11. Agarwal R, Domowicz MS, Schwartz NB, Henry J, Medintz I, Delehanty JB, Stewart MH, Susumu K, Huston AL, Deschamps JR, Dawson PE, Palomo V, Dawson G. Delivery and tracking of quantum dot peptide bioconjugates in an intact developing avian brain. ACS Chem Neurosci. 2015 Mar 18; 6(3):494-504. PMID: 25688887; PMCID: PMC5056627.
      Citations: 22     Fields:    Translation:Animals
    12. Foxley S, Domowicz M, Karczmar GS, Schwartz N. 3D high spectral and spatial resolution imaging of ex vivo mouse brain. Med Phys. 2015 Mar; 42(3):1463-72. PMID: 25735299; PMCID: PMC5148176.
      Citations: 6     Fields:    Translation:Animals
    13. Szuchet S, Nielsen LL, Domowicz MS, Austin JR, Arvanitis DL. CNS myelin sheath is stochastically built by homotypic fusion of myelin membranes within the bounds of an oligodendrocyte process. J Struct Biol. 2015 Apr; 190(1):56-72. PMID: 25682762.
      Citations: 7     Fields:    Translation:AnimalsCells
    14. In "Mimicking the Extracellular Matrix: The Intersection of Matrix Biology and Biomaterials" Ed. W. Murphy and G. Hudalla. Matrix Biology: Gradients and patterns within the extracellular matrix. 2015; 31-64.
    15. Lauing KL, Cortes M, Domowicz MS, Henry JG, Baria AT, Schwartz NB. Aggrecan is required for growth plate cytoarchitecture and differentiation. Dev Biol. 2014 Dec 15; 396(2):224-36. PMID: 25446537; PMCID: PMC4261049.
      Citations: 46     Fields:    Translation:AnimalsCells
    16. Schwartz NB, Domowicz MS. Chemistry and function of glycosaminoglycans in the nervous system. Adv Neurobiol. 2014; 9:89-115. PMID: 25151376.
      Citations: 10     Fields:    
    17. In: Encyclopedia of Endocrine Diseases. Chondrodysplasias. 2014. View Publication.
    18. Mis EK, Liem KF, Kong Y, Schwartz NB, Domowicz M, Weatherbee SD. Forward genetics defines Xylt1 as a key, conserved regulator of early chondrocyte maturation and skeletal length. Dev Biol. 2014 Jan 01; 385(1):67-82. PMID: 24161523; PMCID: PMC3895954.
      Citations: 26     Fields:    Translation:AnimalsCells
    19. Boeneman K, Delehanty JB, Blanco-Canosa JB, Susumu K, Stewart MH, Oh E, Huston AL, Dawson G, Ingale S, Walters R, Domowicz M, Deschamps JR, Algar WR, Dimaggio S, Manono J, Spillmann CM, Thompson D, Jennings TL, Dawson PE, Medintz IL. Selecting improved peptidyl motifs for cytosolic delivery of disparate protein and nanoparticle materials. ACS Nano. 2013 May 28; 7(5):3778-96. PMID: 23710591; PMCID: PMC3880025.
      Citations: 31     Fields:    Translation:HumansAnimalsCells
    20. Cortes M, Mensch JR, Domowicz M, Schwartz NB. Proteoglycans: gene cloning. Methods Mol Biol. 2012; 836:3-21. PMID: 22252624.
      Citations: 1     Fields:    Translation:Animals
    21. Szuchet S, Nielsen JA, Lovas G, Domowicz MS, de Velasco JM, Maric D, Hudson LD. The genetic signature of perineuronal oligodendrocytes reveals their unique phenotype. Eur J Neurosci. 2011 Dec; 34(12):1906-22. PMID: 22132705; PMCID: PMC4286392.
      Citations: 14     Fields:    Translation:AnimalsCells
    22. Domowicz MS, Henry JG, Wadlington N, Navarro A, Kraig RP, Schwartz NB. Astrocyte precursor response to embryonic brain injury. Brain Res. 2011 May 10; 1389:35-49. PMID: 21396923; PMCID: PMC3097075.
      Citations: 14     Fields:    Translation:AnimalsCells
    23. Mitchell HM, White DM, Domowicz MS, Kraig RP. Cold pre-conditioning neuroprotection depends on TNF-a and is enhanced by blockade of interleukin-11. J Neurochem. 2011 Apr; 117(2):187-96. PMID: 21070241; PMCID: PMC3635118.
      Citations: 16     Fields:    Translation:AnimalsCells
    24. In: Encyclopedia of Life Sciences (ELS). Oligodendrocytes. 2010. View Publication.
    25. Domowicz MS, Cortes M, Henry JG, Schwartz NB. Aggrecan modulation of growth plate morphogenesis. Dev Biol. 2009 May 15; 329(2):242-57. PMID: 19268444; PMCID: PMC2810547.
      Citations: 45     Fields:    Translation:AnimalsCells
    26. King LA, Schwartz NB, Domowicz MS. Glial migratory streams in the developing hindbrain: a slice culture approach. J Neurosci Methods. 2009 Feb 15; 177(1):30-43. PMID: 18948137; PMCID: PMC2677068.
      Citations: 2     Fields:    Translation:AnimalsCells
    27. Domowicz MS, Sanders TA, Ragsdale CW, Schwartz NB. Aggrecan is expressed by embryonic brain glia and regulates astrocyte development. Dev Biol. 2008 Mar 01; 315(1):114-24. PMID: 18207138; PMCID: PMC2408532.
      Citations: 30     Fields:    Translation:AnimalsCells
    28. Pirok EW, Domowicz MS, Henry J, Wang Y, Santore M, Mueller MM, Schwartz NB. APBP-1, a DNA/RNA-binding protein, interacts with the chick aggrecan regulatory region. J Biol Chem. 2005 Oct 21; 280(42):35606-16. PMID: 16100116.
      Citations: 2     Fields:    Translation:AnimalsCells
    29. Szuchet S, Plachetzki DC, Seeger MA, Domowicz MS, Szele FG. NOVOcan: a molecular link among selected glial cells. Biophys Chem. 2004 Mar 01; 108(1-3):245-58. PMID: 15043933.
      Citations:    Fields:    Translation:HumansAnimalsCells
    30. Schwartz NB, Domowicz M. Proteoglycans in brain development. Glycoconj J. 2004; 21(6):329-41. PMID: 15514481.
      Citations: 26     Fields:    Translation:Animals
    31. Domowicz MS, Mangoura D, Schwartz NB. Aggrecan regulates telencephalic neuronal aggregation in culture. Brain Res Dev Brain Res. 2003 Jul 12; 143(2):207-16. PMID: 12855192.
      Citations: 4     Fields:    Translation:AnimalsCells
    32. Domowicz MS, Mueller MM, Novak TE, Schwartz LE, Schwartz NB. Developmental expression of the HNK-1 carbohydrate epitope on aggrecan during chondrogenesis. Dev Dyn. 2003 Jan; 226(1):42-50. PMID: 12508223.
      Citations: 7     Fields:    Translation:AnimalsCells
    33. Schwartz NB, Domowicz M. Chondrodysplasias due to proteoglycan defects. Glycobiology. 2002 Apr; 12(4):57R-68R. PMID: 12042245.
      Citations: 48     Fields:    Translation:Animals
    34. Domowicz MS, Pirok EW, Novak TE, Schwartz NB. Role of the C-terminal G3 domain in sorting and secretion of aggrecan core protein and ubiquitin-mediated degradation of accumulated mutant precursors. J Biol Chem. 2000 Nov 10; 275(45):35098-105. PMID: 11063750.
      Citations: 10     Fields:    Translation:AnimalsCells
    35. Domowicz M, Mangoura D, Schwartz NB. Cell specific-chondroitin sulfate proteoglycan expression during CNS morphogenesis in the chick embryo. Int J Dev Neurosci. 2000 Nov; 18(7):629-41. PMID: 10978841.
      Citations: 7     Fields:    Translation:AnimalsCells
    36. Schwartz NB, Pirok EW, Mensch JR, Domowicz MS. Domain organization, genomic structure, evolution, and regulation of expression of the aggrecan gene family. Prog Nucleic Acid Res Mol Biol. 1999; 62:177-225. PMID: 9932455.
      Citations: 15     Fields:    Translation:HumansAnimalsCells
    37. Kurima K, Warman ML, Krishnan S, Domowicz M, Krueger RC, Deyrup A, Schwartz NB. A member of a family of sulfate-activating enzymes causes murine brachymorphism. Proc Natl Acad Sci U S A. 1998 Jul 21; 95(15):8681-5. PMID: 9671738; PMCID: PMC21136.
      Citations: 37     Fields:    Translation:AnimalsCells
    38. Immergluck LC, Domowicz MS, Schwartz NB, Herold BC. Viral and cellular requirements for entry of herpes simplex virus type 1 into primary neuronal cells. J Gen Virol. 1998 Mar; 79 ( Pt 3):549-59. PMID: 9519833.
      Citations: 10     Fields:    Translation:HumansAnimalsCells
    39. Domowicz M, Krueger RC, Li H, Mangoura D, Vertel BM, Schwartz NB. The nanomelic mutation in the aggrecan gene is expressed in chick chondrocytes and neurons. Int J Dev Neurosci. 1996 Jun; 14(3):191-201. PMID: 8842798.
      Citations: 4     Fields:    Translation:AnimalsCells
    40. Pettway Z, Domowicz M, Schwartz NB, Bronner-Fraser M. Age-dependent inhibition of neural crest migration by the notochord correlates with alterations in the S103L chondroitin sulfate proteoglycan. Exp Cell Res. 1996 May 25; 225(1):195-206. PMID: 8635512.
      Citations: 12     Fields:    Translation:Animals
    41. Li H, Domowicz M, Hennig A, Schwartz NB. S103L reactive chondroitin sulfate proteoglycan (aggrecan) mRNA expressed in developing chick brain and cartilage is encoded by a single gene. Brain Res Mol Brain Res. 1996 Mar; 36(2):309-21. PMID: 8965652.
      Citations: 8     Fields:    Translation:Animals
    42. Schwartz NB, Domowicz M, Krueger RC, Li H, Mangoura D. Brain aggrecan. Perspect Dev Neurobiol. 1996; 3(4):291-306. PMID: 9117261.
      Citations: 11     Fields:    Translation:HumansAnimals
    43. Li H, Deyrup A, Mensch JR, Domowicz M, Konstantinidis AK, Schwartz NB. The isolation and characterization of cDNA encoding the mouse bifunctional ATP sulfurylase-adenosine 5'-phosphosulfate kinase. J Biol Chem. 1995 Dec 08; 270(49):29453-9. PMID: 7493984.
      Citations: 12     Fields:    Translation:HumansAnimalsCells
    44. Domowicz M, Li H, Hennig A, Henry J, Vertel BM, Schwartz NB. The biochemically and immunologically distinct CSPG of notochord is a product of the aggrecan gene. Dev Biol. 1995 Oct; 171(2):655-64. PMID: 7556944.
      Citations: 15     Fields:    Translation:AnimalsCells
    45. Kivatinitz SC, Caputto BL, Caputto R, Domowicz MS. Synthesis and translocation of gangliosides and glycoproteins during urethane anesthesia. J Neurochem. 1988 May; 50(5):1369-74. PMID: 2834510.
      Citations:    Fields:    Translation:AnimalsCells
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