Keywords
Last Name

Maria A. Kukuruzinska, PhD

TitleProfessor of Molecular & Cell Biology
InstitutionBoston University Henry M. Goldman School of Dental Medicine
DepartmentMolecular & Cell Biology
Address75 E. Newton St Evans Building
Boston MA 02118
Phone(617) 638-4859
ORCID ORCID Icon0000-0001-5314-1454
Other Positions
TitleAssociate Dean of Research
InstitutionBoston University Henry M. Goldman School of Dental Medicine
DepartmentDean’s Office

TitleResearch Assistant Professor of Biochemistry
InstitutionBoston University School of Medicine
DepartmentBiochemistry

TitleMentor for Graduate Medical Students
InstitutionBoston University School of Medicine, Division of Graduate Medical Sciences

TitleProgram Director of Predoctoral Research Program
InstitutionBoston University Henry M. Goldman School of Dental Medicine

 Research Expertise & Professional Interests
The long term goal of my work is to elucidate the regulatory mechanisms underlying the interactions between the metabolic pathway of protein N-glycosylation and intercellular adhesion in tissue development and disease.

Cross Talk Between Protein N-glycosylation, E-cadherin-mediated Cell-Cell Adhesion and Canonical Wnt Signaling. Studies in my laboratory have unveiled a critical role for N-glycosylation in the function of E-cadherin, a major epithelial cell-cell adhesion receptor that forms adherens junctions (AJs). They have shown that N-glycosylation affects the maturity of AJs and the assembly of tight junctions (TJs), as well as cytoskeletal dynamics. On a molecular level, the N-glycosylation status of E-cadherin is controlled by the DPAGT1 gene, the first gene in the N-glycosylation pathway and its key regulator. At the same time, E-cadherin junctions regulate DPAGT1 expression, indicating the existence of a bidirectional feedback loop between the metabolic pathway of protein N-glycosylation and cell-cell adhesion. Current studies in my laboratory are aimed at elucidating the molecular mechanism via which AJs regulate N-glycosylation.

Mechanisms Underlying Salivary Gland Development. Another major project in my laboratory focuses on the key mechanisms that drive submandibular gland (SMG) development. We have shown that E-cadherin regulates major events during SMG morphogenesis, including proliferation of acinar and ductal progenitors, formation of new buds and survival of ductal progenitors during tubulogenesis. E-cadherin also plays an important role in the planar cell polarity pathway that drives ductal axis extension during SMG morphogenesis. These developmental functions of E-cadherin are regulated by N-glycosylation. Our ongoing studies focus on the molecular characterization of how N-glycosylation and E-cadherin impact acinar and ductal cell fate specification and drive the formation of mature SMG structures.

Molecular Basis of Oral Cancer. The conceptual framework of our mechanistic studies is being applied to investigation of the development and progression of oral cancer. Our recent work has shown that aberrant activation of cellular N-glycosylation promotes the development and progression of oral squamous cell carcinoma (OSCC). Partial inhibition of cellular N-glycosylation in oral cancer cell lines leads to the stabilization of intercellular adhesion, which then drives the mesenchymal to epithelial transition. Current studies examine the molecular basis of over-expression of DPAGT1 in OSCC and its relationship to the downstream signaling pathways that impact E-cadherin’s tumor suppressive function.

Molecular Basis of Sjogren’s Syndrome. Recently, we have initiated studies on Sjogren’s Syndrome (SS), an autoimmune disease that affects salivary and lacrimal glands. Although Sjogren’s disease has long been thought to be caused by lymphocytic infiltration, our recent work has suggested that defective intercellular adhesion is one of the underlying causes of this disease. To expedite the deciphering of the molecular basis of SS and to promote the development of new diagnostics, I co-founded an international collaboration, the Norwegian-United States Initiative on Sjogren’s Syndrome (NUSSIS), that brings together basic researchers and clinicians from the University of Oslo, the University at Albany - SUNY, University of Florida and from the Boston University School of Dental Medicine.

 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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  1. Vargas DA, Sun M, Sadykov K, Kukuruzinska MA, Zaman MH. The Integrated Role of Wnt/ß-Catenin, N-Glycosylation, and E-Cadherin-Mediated Adhesion in Network Dynamics. PLoS Comput Biol. 2016 Jul; 12(7):e1005007. PMID: 27427963.
    View in: PubMed
  2. Stanford EA, Ramirez-Cardenas A, Wang Z, Novikov O, Alamoud K, Koutrakis P, Mizgerd JP, Genco CA, Kukuruzinska M, Monti S, Bais MV, Sherr DH. Role for the Aryl Hydrocarbon Receptor and Diverse Ligands in Oral Squamous Cell Carcinoma Migration and Tumorigenesis. Mol Cancer Res. 2016 Aug; 14(8):696-706. PMID: 27130942.
    View in: PubMed
  3. Kartha VK, Stawski L, Han R, Haines P, Gallagher G, Noonan V, Kukuruzinska M, Monti S, Trojanowska M. PDGFRß Is a Novel Marker of Stromal Activation in Oral Squamous Cell Carcinomas. PLoS One. 2016; 11(4):e0154645. PMID: 27128408.
    View in: PubMed
  4. Rebustini IT, Vlahos M, Packer T, Kukuruzinska MA, Maas RL. An integrated miRNA functional screening and target validation method for organ morphogenesis. Sci Rep. 2016 Mar 16; 6:23215. PMID: 26980315.
    View in: PubMed
  5. Hiemer SE, Zhang L, Kartha VK, Packer TS, Almershed M, Noonan V, Kukuruzinska M, Bais MV, Monti S, Varelas X. A YAP/TAZ-Regulated Molecular Signature Is Associated with Oral Squamous Cell Carcinoma. Mol Cancer Res. 2015 Jun; 13(6):957-68. PMID: 25794680.
    View in: PubMed
  6. Bais MV, Kukuruzinska M, Trackman PC. Orthotopic non-metastatic and metastatic oral cancer mouse models. Oral Oncol. 2015 May; 51(5):476-82. PMID: 25682387.
    View in: PubMed
  7. Varelas X, Kukuruzinska MA. Head and neck cancer: from research to therapy and cure. Ann N Y Acad Sci. 2014 Dec; 1333:1-32. PMID: 25532687.
    View in: PubMed
  8. Varelas X, Bouchie MP, Kukuruzinska MA. Protein N-glycosylation in oral cancer: dysregulated cellular networks among DPAGT1, E-cadherin adhesion and canonical Wnt signaling. Glycobiology. 2014 Jul; 24(7):579-91. PMID: 24742667.
    View in: PubMed
  9. Enger TB, Samad-Zadeh A, Bouchie MP, Skarstein K, Galtung HK, Mera T, Walker J, Menko AS, Varelas X, Faustman DL, Jensen JL, Kukuruzinska MA. The Hippo signaling pathway is required for salivary gland development and its dysregulation is associated with Sjogren's syndrome. Lab Invest. 2013 Nov; 93(11):1203-18. PMID: 24080911.
    View in: PubMed
  10. Liu G, Sengupta PK, Jamal B, Yang HY, Bouchie MP, Lindner V, Varelas X, Kukuruzinska MA. N-glycosylation induces the CTHRC1 protein and drives oral cancer cell migration. J Biol Chem. 2013 Jul 12; 288(28):20217-27. PMID: 23703614.
    View in: PubMed
  11. Liu G, Kukuruzinska MA, Xu X. Ror2 may be downregulated in oral squamous cell carcinoma. Oral Surg Oral Med Oral Pathol Oral Radiol. 2013 Jul; 116(1):120. PMID: 23465658.
    View in: PubMed
  12. Sengupta PK, Bouchie MP, Nita-Lazar M, Yang HY, Kukuruzinska MA. Coordinate regulation of N-glycosylation gene DPAGT1, canonical Wnt signaling and E-cadherin adhesion. J Cell Sci. 2013 Jan 15; 126(Pt 2):484-96. PMID: 23178939.
    View in: PubMed
  13. Jamal B, Sengupta PK, Gao ZN, Nita-Lazar M, Amin B, Jalisi S, Bouchie MP, Kukuruzinska MA. Aberrant amplification of the crosstalk between canonical Wnt signaling and N-glycosylation gene DPAGT1 promotes oral cancer. Oral Oncol. 2012 Jun; 48(6):523-9. PMID: 22341307.
    View in: PubMed
  14. Sengupta PK, Bouchie MP, Kukuruzinska MA. N-glycosylation gene DPAGT1 is a target of the Wnt/beta-catenin signaling pathway. J Biol Chem. 2010 Oct 8; 285(41):31164-73. PMID: 20693288.
    View in: PubMed
  15. Nita-Lazar M, Rebustini I, Walker J, Kukuruzinska MA. Hypoglycosylated E-cadherin promotes the assembly of tight junctions through the recruitment of PP2A to adherens junctions. Exp Cell Res. 2010 Jul 1; 316(11):1871-84. PMID: 20156436.
    View in: PubMed
  16. Jamal BT, Nita-Lazar M, Gao Z, Amin B, Walker J, Kukuruzinska MA. N-glycosylation status of E-cadherin controls cytoskeletal dynamics through the organization of distinct ß-catenin- and ?-catenin-containing AJs. Cell Health Cytoskelet. 2009 Sep 16; 2009(1):67-80. PMID: 20502620.
    View in: PubMed
  17. Nita-Lazar M, Noonan V, Rebustini I, Walker J, Menko AS, Kukuruzinska MA. Overexpression of DPAGT1 leads to aberrant N-glycosylation of E-cadherin and cellular discohesion in oral cancer. Cancer Res. 2009 Jul 15; 69(14):5673-80. PMID: 19549906.
    View in: PubMed
  18. Walker JL, Menko AS, Khalil S, Rebustini I, Hoffman MP, Kreidberg JA, Kukuruzinska MA. Diverse roles of E-cadherin in the morphogenesis of the submandibular gland: insights into the formation of acinar and ductal structures. Dev Dyn. 2008 Nov; 237(11):3128-41. PMID: 18816447.
    View in: PubMed
  19. Tsao PN, Chen F, Izvolsky KI, Walker J, Kukuruzinska MA, Lu J, Cardoso WV. Gamma-secretase activation of notch signaling regulates the balance of proximal and distal fates in progenitor cells of the developing lung. J Biol Chem. 2008 Oct 24; 283(43):29532-44. PMID: 18694942.
    View in: PubMed
  20. Liwosz A, Lei T, Kukuruzinska MA. N-glycosylation affects the molecular organization and stability of E-cadherin junctions. J Biol Chem. 2006 Aug 11; 281(32):23138-49. PMID: 16682414.
    View in: PubMed
  21. Mendelsohn RD, Helmerhorst EJ, Cipollo JF, Kukuruzinska MA. A hypomorphic allele of the first N-glycosylation gene, ALG7, causes mitochondrial defects in yeast. Biochim Biophys Acta. 2005 May 25; 1723(1-3):33-44. PMID: 15794922.
    View in: PubMed
  22. Rex S, Kukuruzinska MA, Istfan NW. Inhibition of DNA replication by fish oil-treated cytoplasm is counteracted by fish oil-treated nuclear extract. Am J Physiol Cell Physiol. 2002 Nov; 283(5):C1365-75. PMID: 12372797.
    View in: PubMed
  23. Menko AS, Zhang L, Schiano F, Kreidberg JA, Kukuruzinska MA. Regulation of cadherin junctions during mouse submandibular gland development. Dev Dyn. 2002 Jul; 224(3):321-33. PMID: 12112462.
    View in: PubMed
  24. Klebl B, Kozian D, Leberer E, Kukuruzinska MA. A comprehensive analysis of gene expression profiles in a yeast N-glycosylation mutant. Biochem Biophys Res Commun. 2001 Aug 31; 286(4):714-20. PMID: 11520056.
    View in: PubMed
  25. Menko AS, Kreidberg JA, Ryan TT, Van Bockstaele E, Kukuruzinska MA. Loss of alpha3beta1 integrin function results in an altered differentiation program in the mouse submandibular gland. Dev Dyn. 2001 Apr; 220(4):337-49. PMID: 11307167.
    View in: PubMed
  26. Fernandes RP, Cotanche DA, Lennon-Hopkins K, Erkan F, Menko AS, Kukuruzinska MA. Differential expression of proliferative, cytoskeletal, and adhesive proteins during postnatal development of the hamster submandibular gland. Histochem Cell Biol. 1999 Feb; 111(2):153-62. PMID: 10090576.
    View in: PubMed
  27. Kukuruzinska MA, Lennon-Hopkins K. ALG gene expression and cell cycle progression. Biochim Biophys Acta. 1999 Jan 6; 1426(2):359-72. PMID: 9878828.
    View in: PubMed
  28. Fernandes R, Fox M, Cotanche D, Lennon K, Kukuruzinska MA. Confocal imaging of gene expression during hamster submandibular gland biogenesis. Ann N Y Acad Sci. 1998 Apr 15; 842:212-6. PMID: 9599314.
    View in: PubMed
  29. Lennon K, Bird A, Kukuruzinska MA. Molecular dissection of the genetic targets of ALG7 in the serpentine receptor-mediated signal transduction pathway in yeast. Ann N Y Acad Sci. 1998 Apr 15; 842:195-8. PMID: 9599310.
    View in: PubMed
  30. Huang GT, Lennon K, Kukuruzinska MA. Characterization of multiple transcripts of the hamster dolichol-P-dependent N-acetylglucosamine-1-P transferase suggests functionally complex expression. Mol Cell Biochem. 1998 Apr; 181(1-2):97-106. PMID: 9562246.
    View in: PubMed
  31. Kukuruzinska MA, Lennon K. Protein N-glycosylation: molecular genetics and functional significance. Crit Rev Oral Biol Med. 1998; 9(4):415-48. PMID: 9825220.
    View in: PubMed
  32. Lennon K, Bird A, Kukuruzinska MA. Deregulation of the first N-glycosylation gene, ALG7, perturbs the expression of G1 cyclins and cell cycle arrest in Saccharomyces cerevisiae. Biochem Biophys Res Commun. 1997 Aug 28; 237(3):562-5. PMID: 9299404.
    View in: PubMed
  33. Lennon K, Bird A, Chen YF, Pretel R, Kukuruzinska MA. The dual role of mRNA half-lives in the expression of the yeast ALG7 gene. Mol Cell Biochem. 1997 Apr; 169(1-2):95-106. PMID: 9089636.
    View in: PubMed
  34. Lennon K, Pretel R, Kesselheim J, te Heesen S, Kukuruzinska MA. Proliferation-dependent differential regulation of the dolichol pathway genes in Saccharomyces cerevisiae. Glycobiology. 1995 Sep; 5(6):633-42. PMID: 8563151.
    View in: PubMed
  35. Pretel R, Lennon K, Bird A, Kukuruzinska MA. Expression of the first N-glycosylation gene in the dolichol pathway, ALG7, is regulated at two major control points in the G1 phase of the Saccharomyces cerevisiae cell cycle. Exp Cell Res. 1995 Aug; 219(2):477-86. PMID: 7641800.
    View in: PubMed
  36. Kukuruzinska MA, Lennon K. Diminished activity of the first N-glycosylation enzyme, dolichol-P-dependent N-acetylglucosamine-1-P transferase (GPT), gives rise to mutant phenotypes in yeast. Biochim Biophys Acta. 1995 Feb 22; 1247(1):51-9. PMID: 7873591.
    View in: PubMed
  37. Mota OM, Huang GT, Kukuruzinska MA. Developmental regulation and tissue-specific expression of hamster dolichol-P-dependent N-acetylglucosamine-1-P transferase (GPT). Biochem Biophys Res Commun. 1994 Oct 14; 204(1):284-91. PMID: 7945372.
    View in: PubMed
  38. Kukuruzinska MA, Lennon K. Growth-related coordinate regulation of the early N-glycosylation genes in yeast. Glycobiology. 1994 Aug; 4(4):437-43. PMID: 7827405.
    View in: PubMed
  39. Kukuruzinska MA, Apekin V, Lamkin MS, Hiltz A, Rodriguez A, Lin CC, Paz MA, Oppenheim FG. Antisense RNA to the first N-glycosylation gene, ALG7, inhibits protein N-glycosylation and secretion by Xenopus oocytes. Biochem Biophys Res Commun. 1994 Feb 15; 198(3):1248-54. PMID: 7509600.
    View in: PubMed
  40. Jackson BJ, Kukuruzinska MA, Robbins P. Biosynthesis of asparagine-linked oligosaccharides in Saccharomyces cerevisiae: the alg2 mutation. Glycobiology. 1993 Aug; 3(4):357-64. PMID: 8400550.
    View in: PubMed
  41. Kukuruzinska, M.A . Enzymes at work (RE: Regulation of Enzyme Activity, J.H. Ottaway). IRL Press. 1989; 39(10):738-740 .
    View in: External Website
  42. Kukuruzinska MA, Robbins PW. Protein glycosylation in yeast: transcript heterogeneity of the ALG7 gene. Proc Natl Acad Sci U S A. 1987 Apr; 84(8):2145-9. PMID: 3031666.
    View in: PubMed
  43. Kukuruzinska MA, Bergh ML, Jackson BJ. Protein glycosylation in yeast. Annu Rev Biochem. 1987; 56:915-44. PMID: 3304149.
    View in: PubMed
  44. Meadow, N.D., Kukuruzinska, M.A. and Roseman, S. . The Bacterial Phosphoenolpyruvate:Sugar Phosphotransferase System. The Enzymes if Biological Membranes. Plenum Press. New York. 1985; 523-559.
  45. Kukuruzinska MA, Turner BW, Ackers GK, Roseman S. Subunit association of enzyme I of the Salmonella typhimurium phosphoenolpyruvate: glycose phosphotransferase system. Temperature dependence and thermodynamic properties. J Biol Chem. 1984 Oct 10; 259(19):11679-81. PMID: 6384212.
    View in: PubMed
  46. Fox D, Kukuruzinska M, Liu KD, Meadow ND, Saffen D, Roseman S. Regulation of sugar transport by the bacterial phosphoenolpyruvate: glucose phosphotransferase system. Biochem Soc Trans. 1984 Apr; 12(2):155-7. PMID: 6373429.
    View in: PubMed
  47. Kukuruzinska MA, Harrington WF, Roseman S. Sugar transport by the bacterial phosphotransferase system. Studies on the molecular weight and association of enzyme I. J Biol Chem. 1982 Dec 10; 257(23):14470-6. PMID: 6754729.
    View in: PubMed
  48. Weigel N, Waygood EB, Kukuruzinska MA, Nakazawa A, Roseman S. Sugar transport by the bacterial phosphotransferase system. Isolation and characterization of enzyme I from Salmonella typhimurium. J Biol Chem. 1982 Dec 10; 257(23):14461-9. PMID: 6754728.
    View in: PubMed
  49. Weigel N, Kukuruzinska MA, Nakazawa A, Waygood EB, Roseman S. Sugar transport by the bacterial phosphotransferase system. Phosphoryl transfer reactions catalyzed by enzyme I of Salmonella typhimurium. J Biol Chem. 1982 Dec 10; 257(23):14477-91. PMID: 6754730.
    View in: PubMed
  50. Roseman S, Meadow ND, Kukuruzinska MA. Phosphoenolpyruvate:glycose phosphotransferase system. General description and assay principles. Methods Enzymol. 1982; 90 Pt E:417-23. PMID: 6759858.
    View in: PubMed
  51. Kukuruzinska MA, Weigel N, Waygood EB. Enzyme I from salmonella typhimurium. Methods Enzymol. 1982; 90 Pt E:431-6. PMID: 6759860.
    View in: PubMed
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