Maria A. Kukuruzinska, PhD
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Title Professor
Institution Boston University Goldman School of Dental Medicine
Department Molecular & Cell Biology
Address 75 E. Newton St
 Boston, MA 02118
Telephone (617) 638-4859
Email
Other Positions
Title Research Assistant Professor
Institution Boston University School of Medicine
Department Biochemistry
 
Title Associate Dean for Research
Institution Boston University Goldman School of Dental Medicine
Department Dean’s Office
 
Title Graduate Faculty (Primary Mentor of Grad Students)
Institution Boston University School of Medicine
Department Graduate Medical Sciences, Division of
 
Title Program Director of Predoctoral Research Program
Institution Boston University 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
1. 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.
  View in: PubMed
 
2. 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.
  View in: PubMed
 
3. 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.
  View in: PubMed
 
4. 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.
  View in: PubMed
 
5. 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.
  View in: PubMed
 
6. 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.
  View in: PubMed
 
7. 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.
  View in: PubMed
 
8. 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.
  View in: PubMed
 
9. 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.
  View in: PubMed
 
10. 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.
  View in: PubMed
 
11. 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.
  View in: PubMed
 
12. 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.
  View in: PubMed
 
13. 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.
  View in: PubMed
 
14. 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.
  View in: PubMed
 
15. 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.
  View in: PubMed
 
16. Kukuruzinska MA, Lennon-Hopkins K. ALG gene expression and cell cycle progression. Biochim Biophys Acta. 1999 Jan 6; 1426(2):359-72.
  View in: PubMed
 
17. 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.
  View in: PubMed
 
18. 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.
  View in: PubMed
 
19. 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.
  View in: PubMed
 
20. Kukuruzinska MA, Lennon K. Protein N-glycosylation: molecular genetics and functional significance. Crit Rev Oral Biol Med. 1998; 9(4):415-48.
  View in: PubMed
 
21. 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.
  View in: PubMed
 
22. 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.
  View in: PubMed
 
23. 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.
  View in: PubMed
 
24. 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.
  View in: PubMed
 
25. 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.
  View in: PubMed
 
26. 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.
  View in: PubMed
 
27. Kukuruzinska MA, Lennon K. Growth-related coordinate regulation of the early N-glycosylation genes in yeast. Glycobiology. 1994 Aug; 4(4):437-43.
  View in: PubMed
 
28. 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.
  View in: PubMed
 
29. Jackson BJ, Kukuruzinska MA, Robbins P. Biosynthesis of asparagine-linked oligosaccharides in Saccharomyces cerevisiae: the alg2 mutation. Glycobiology. 1993 Aug; 3(4):357-64.
  View in: PubMed
 
30. Kukuruzinska, M.A . Enzymes at work (RE: Regulation of Enzyme Activity, J.H. Ottaway). IRL Press. 1989; 39(10):738-740 .
  View in: External Web Site
 
31. 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.
  View in: PubMed
 
32. Kukuruzinska MA, Bergh ML, Jackson BJ. Protein glycosylation in yeast. Annu Rev Biochem. 1987; 56:915-44.
  View in: PubMed
 
33. Meadow, N.D., Kukuruzinska, M.A. and Roseman, S. The Bacterial Phosphoenolpyruvate:Sugar Phosphotransferase System. The Enzymes if Biological Membranes. New York:Plenum Press. 1985; 523-559.
 
34. 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.
  View in: PubMed
 
35. 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.
  View in: PubMed
 
36. 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.
  View in: PubMed
 
37. 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.
  View in: PubMed
 
38. 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.
  View in: PubMed
 
39. Roseman S, Meadow ND, Kukuruzinska MA. Phosphoenolpyruvate:glycose phosphotransferase system. General description and assay principles. Methods Enzymol. 1982; 90 Pt E:417-23.
  View in: PubMed
 
40. Kukuruzinska MA, Weigel N, Waygood EB. Enzyme I from salmonella typhimurium. Methods Enzymol. 1982; 90 Pt E:431-6.
  View in: PubMed
 
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Co-Authors  
Cardoso, Wellington
Chen, Felicia
Helmerhorst, Eva
Lu, Jining
Schiano, Frank
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