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Miriam Domowicz

TitleResearch Associate Professor
InstitutionUniversity of Chicago
DepartmentPediatrics-Kennedy Center
AddressChicago IL 60637
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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 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.
    List All   |   Timeline
    1. Domowicz MS, Chan WC, Claudio-Vázquez P, Henry JG, Ware CB, Andrade J, Dawson G, Schwartz NB. Global Brain Transcriptome Analysis of a Tpp1 Neuronal Ceroid Lipofuscinoses Mouse Model. ASN Neuro. 2019 Jan-Dec; 11:1759091419843393. PMID: 31003587.
      View in: PubMed
    2. Schwartz NB, Domowicz MS. Proteoglycans in brain development and pathogenesis. FEBS Lett. 2018 12; 592(23):3791-3805. PMID: 29513405.
      View in: PubMed
    3. 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.
      View in: PubMed
    4. 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.
      View in: PubMed
    5. 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.
      View in: PubMed
    6. 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.
      View in: PubMed
    7. 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.
      View in: PubMed
    8. Schwartz NB, Domowicz MS. Chemistry and function of glycosaminoglycans in the nervous system. Adv Neurobiol. 2014; 9:89-115. PMID: 25151376.
      View in: PubMed
    9. 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.
      View in: PubMed
    10. 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.
      View in: PubMed
    11. Cortes M, Mensch JR, Domowicz M, Schwartz NB. Proteoglycans: gene cloning. Methods Mol Biol. 2012; 836:3-21. PMID: 22252624.
      View in: PubMed
    12. 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.
      View in: PubMed
    13. 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.
      View in: PubMed
    14. 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.
      View in: PubMed
    15. 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.
      View in: PubMed
    16. 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.
      View in: PubMed
    17. 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.
      View in: PubMed
    18. 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.
      View in: PubMed
    19. 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.
      View in: PubMed
    20. Schwartz NB, Domowicz M. Proteoglycans in brain development. Glycoconj J. 2004; 21(6):329-41. PMID: 15514481.
      View in: PubMed
    21. 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.
      View in: PubMed
    22. 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.
      View in: PubMed
    23. Schwartz NB, Domowicz M. Chondrodysplasias due to proteoglycan defects. Glycobiology. 2002 Apr; 12(4):57R-68R. PMID: 12042245.
      View in: PubMed
    24. 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.
      View in: PubMed
    25. 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.
      View in: PubMed
    26. 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.
      View in: PubMed
    27. 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.
      View in: PubMed
    28. 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.
      View in: PubMed
    29. 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.
      View in: PubMed
    30. 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.
      View in: PubMed
    31. 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.
      View in: PubMed
    32. Schwartz NB, Domowicz M, Krueger RC, Li H, Mangoura D. Brain aggrecan. Perspect Dev Neurobiol. 1996; 3(4):291-306. PMID: 9117261.
      View in: PubMed
    33. 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.
      View in: PubMed
    34. 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.
      View in: PubMed
    35. Domowicz MS, Kivatinitz SC, Caputto BL, Caputto R. Synthesis and translocation of gangliosides and glycoproteins during urethane anesthesia. J Neurochem. 1988 May; 50(5):1369-74. PMID: 2834510.
      View in: PubMed
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