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 , Dean’s Office, Boston University Henry M. Goldman School of Dental Medicine
- Research Assistant Professor of Biochemistry , 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
- Johns Hopkins University, PhD
- Bryn Mawr College, BA
- Published on 7/27/2017
Alsaqer SF, Tashkandi MM, Kartha VK, Yang YT, Alkheriji Y, Salama A, Varelas X, Kukuruzinska M, Monti S, Bais MV. Inhibition of LSD1 epigenetically attenuates oral cancer growth and metastasis. Oncotarget. 2017 Sep 26; 8(43):73372-73386. PMID: 29088714.
- Published on 7/22/2017
Bais MV, Kukuruzinska M, Trackman PC. Corrigendum to "Orthotopic non-metastatic and metastatic oral cancer mouse models" [Oral Oncol. 51(5) (2015) 476-482]. Oral Oncol. 2017 Sep; 72:201. PMID: 28743466.
- Published on 5/11/2017
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. PMID: 28492365.
- Published on 7/18/2016
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.
- Published on 4/29/2016
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.
- Published on 4/29/2016
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.
- Published on 3/16/2016
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.
- Published on 3/20/2015
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.
- Published on 2/11/2015
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.
- Published on 12/1/2014
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.
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