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
- Acting Chair, Translational Dental Medicine, Boston University Henry M. Goldman School of Dental Medicine
- Research Assistant Professor, Biochemistry & Cell Biology, Boston University Chobanian & Avedisian School of Medicine
- Program Director of Predoctoral Research Program, Boston University Henry M. Goldman School of Dental Medicine
- Associate Director for Basic Sciences, BU-BMC Cancer Center, Boston University
- Member, Evans Center for Interdisciplinary Biomedical Research, Boston University
- Member, Genome Science Institute, Boston University
- Graduate Faculty (Primary Mentor of Grad Students), Boston University Chobanian & Avedisian School of Medicine, Graduate Medical Sciences
- Johns Hopkins University, PhD
- Bryn Mawr College, BA
- Published on 8/4/2023
Khan MM, Frustino J, Villa A, Nguyen BC, Woo SB, Johnson WE, Varelas X, Kukuruzinska M, Monti S. Total RNA sequencing reveals gene expression and microbial alterations shared by oral pre-malignant lesions and cancer. Hum Genomics. 2023 Aug 04; 17(1):72. PMID: 37542347.
- Published on 6/21/2023
Reed ER, Jankowski SA, Spinella AJ, Noonan V, Haddad R, Nomoto K, Matsui J, Bais MV, Varelas X, Kukuruzinska MA, Monti S. ß-catenin/CBP activation of mTORC1 signaling promotes partial epithelial-mesenchymal states in head and neck cancer. Transl Res. 2023 Oct; 260:46-60. PMID: 37353110.
- Published on 3/24/2023
Khan MM, Frustino J, Villa A, Nguyen BC, Woo SB, Johnson WE, Varelas X, Kukuruzinska M, Monti S. Total RNA sequencing reveals gene expression and microbial alterations shared by oral pre-malignant lesions and cancer. bioRxiv. 2023 Mar 24. PMID: 36993637.
- Published on 5/4/2022
Alhousami T, Diny M, Ali F, Shin J, Kumar G, Kumar V, Campbell JD, Noonan V, Hanna GJ, Denis GV, Monti S, Kukuruzinska MA, Varelas X, Bais MV. Inhibition of LSD1 Attenuates Oral Cancer Development and Promotes Therapeutic Efficacy of Immune Checkpoint Blockade and YAP/TAZ Inhibition. Mol Cancer Res. 2022 May 04; 20(5):712-721. PMID: 35105672.
- Published on 5/27/2021
Dela Cruz A, Kartha V, Tilston-Lunel A, Mi R, Reynolds TL, Mingueneau M, Monti S, Jensen JL, Skarstein K, Varelas X, Kukuruzinska MA. Gene expression alterations in salivary gland epithelia of Sjögren's syndrome patients are associated with clinical and histopathological manifestations. Sci Rep. 2021 05 27; 11(1):11154. PMID: 34045583.
- Published on 1/11/2021
Walker JL, Wang W, Lin E, Romisher A, Bouchie MP, Bleaken B, Menko AS, Kukuruzinska MA. Specification of the patterning of a ductal tree during branching morphogenesis of the submandibular gland. Sci Rep. 2021 01 11; 11(1):330. PMID: 33432003.
- Published on 3/23/2020
Chandler KB, Alamoud KA, Stahl VL, Nguyen BC, Kartha VK, Bais MV, Nomoto K, Owa T, Monti S, Kukuruzinska MA, Costello CE. ß-Catenin/CBP inhibition alters epidermal growth factor receptor fucosylation status in oral squamous cell carcinoma. Mol Omics. 2020 06 01; 16(3):195-209. PMID: 32203567.
- Published on 11/12/2018
Yost S, Stashenko P, Choi Y, Kukuruzinska M, Genco CA, Salama A, Weinberg EO, Kramer CD, Frias-Lopez J. Increased virulence of the oral microbiome in oral squamous cell carcinoma revealed by metatranscriptome analyses. Int J Oral Sci. 2018 11 12; 10(4):32. PMID: 30420594.
- Published on 7/20/2018
Kartha VK, Alamoud KA, Sadykov K, Nguyen BC, Laroche F, Feng H, Lee J, Pai SI, Varelas X, Egloff AM, Snyder-Cappione JE, Belkina AC, Bais MV, Monti S, Kukuruzinska MA. Functional and genomic analyses reveal therapeutic potential of targeting ß-catenin/CBP activity in head and neck cancer. Genome Med. 2018 07 20; 10(1):54. PMID: 30029671.
- Published on 6/1/2018
Alamoud KA, Kukuruzinska MA. Emerging Insights into Wnt/ß-catenin Signaling in Head and Neck Cancer. J Dent Res. 2018 06; 97(6):665-673. PMID: 29771197.
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