Maria A. Kukuruzinska, PhD
Professor of Molecular & Cell Biology
Boston University Henry M. Goldman School of Dental Medicine
Dept of Molecular & Cell Biology

PhD, Johns Hopkins University

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.

Associate Dean of Research
Boston University Henry M. Goldman School of Dental Medicine
Dean’s Office

Research Assistant Professor of Biochemistry
Boston University School of Medicine

Mentor for Graduate Medical Students
Boston University School of Medicine, Division of Graduate Medical Sciences

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

Repair, Regeneration and Fibrosis of the Salivary Gland
07/01/2015 - 06/30/2017 (PI)
NIH/National Institute of Dental & Craniofacial Research

Head and Neck Cancer Symposium: From Pathways to Therapies
08/01/2015 - 07/31/2016 (PI)
NIH/National Institute of Dental & Craniofacial Research

Defective Cell Polarity and Hippo Signalling in the Etiology of Sjogren's Syndrome
04/01/2014 - 03/31/2016 (PI)
Biogen Idec

Functional Role of the Hippo Pathway in Sjogren's Syndrome
07/01/2012 - 06/30/2014 (PI)
Sjogren's Syndrome Foundation

Regulation of SMG Development by Adhesion Receptors
05/01/2002 - 04/30/2014 (PI)
NIH/National Institute of Dental & Craniofacial Research

Developmental Expression of the Salivary ALG7 Gene
04/01/1998 - 03/31/2009 (PI)
NIH/National Institute of Dental & Craniofacial Research
5 R01 DE10183 13

Short Term Training: Students in Health Professional Schools
06/01/1998 - 05/31/2003 (PI)
NIH/National Institute of Dental & Craniofacial Research
5 T35 DE07257 05

Role of Cadherins in Salivary Gland Development
07/01/1998 - 06/30/2000 (PI)
Thomas Jefferson University NIH NIDCR

Yr Title Project-Sub Proj Pubs
2016 Repair, Regeneration and Fibrosis of the Salivary Gland 5R21DE024954-02
2015 Head and Neck Cancer Symposium: From Pathways to Therapies 1R13DE025552-01
2013 2013 Salivary Glands and Exocrine Biology Gordon Research Conference 1R13DE023467-01
2012 Regulation of SMG Development by Adhesion Receptors 5R01DE014437-08 3
2011 Regulation of SMG Development by Adhesion Receptors 5R01DE014437-07 3
2010 The Role of E-cadherin N-glycans in Oral Cancer 5R01DE015304-05 9
2010 Regulation of SMG Development by Adhesion Receptors 5R01DE014437-06 3
2009 The Role of E-cadherin N-glycans in Oral Cancer 5R01DE015304-04 9
Showing 10 of 57 results. Show All Results
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.

  1. Szymaniak AD, Mi R, McCarthy SE, Gower AC, Reynolds TL, Mingueneau M, Kukuruzinska M, Varelas X. The Hippo pathway effector YAP is an essential regulator of ductal progenitor patterning in the mouse submandibular gland. Elife. 2017 May 11; 6.View Related Profiles. PMID: 28492365.
  2. 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.View Related Profiles. PMID: 27427963; PMCID: PMC4948889; DOI: 10.1371/journal.pcbi.1005007;.
  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.View Related Profiles. PMID: 27128408; PMCID: PMC4851360; DOI: 10.1371/journal.pone.0154645;.
  4. 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.View Related Profiles. PMID: 27130942; PMCID: PMC4987205; DOI: 10.1158/1541-7786.MCR-16-0069;.
  5. 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; PMCID: PMC4793243; DOI: 10.1038/srep23215;.
  6. 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.View Related Profiles. PMID: 25794680; PMCID: PMC4470857; DOI: 10.1158/1541-7786.MCR-14-0580;.
  7. Bais MV, Kukuruzinska M, Trackman PC. Orthotopic non-metastatic and metastatic oral cancer mouse models. Oral Oncol. 2015 May; 51(5):476-82.View Related Profiles. PMID: 25682387; PMCID: PMC4427342; DOI: 10.1016/j.oraloncology.2015.01.012;.
  8. Varelas X, Kukuruzinska MA. Head and neck cancer: from research to therapy and cure. Ann N Y Acad Sci. 2014 Dec; 1333:1-32.View Related Profiles. PMID: 25532687; DOI: 10.1111/nyas.12613;.
  9. 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.View Related Profiles. PMID: 24742667; PMCID: PMC4038253; DOI: 10.1093/glycob/cwu031;.
  10. 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.View Related Profiles. PMID: 24080911; PMCID: PMC3864807; DOI: 10.1038/labinvest.2013.114;.
Showing 10 of 52 results. Show More

This graph shows the total number of publications by year, by first, middle/unknown, or last author.

Bar chart showing 52 publications over 24 distinct years, with a maximum of 5 publications in 1982

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75 E. Newton St Evans Building
Boston MA 02118
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