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

PhD, Johns Hopkins University
BA, Bryn Mawr College



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.

Diversity, Equity, Inclusion and Accessibility

My research focuses on molecular mechanisms underlying head and neck cancer development and progression to advanced disease. This malignancy disproportionately affects underserved communities and addressing health disparities is an integral part of my work aimed to create a more equitable world.

As a woman, I am personally familiar with some of the challenges of structural inequity. Actively supporting others’ professional development and careers through mentoring is crucial to making scientific research more inclusive. Most of the students, postdoctoral fellows, and junior faculty that I have mentored have been women and/or people of color, and I am committed to making basic science and translational science research more diverse.

Mentoring future generations of scientists and researchers has been an interest of mine throughout my career. I strive to cultivate a respectful and supportive environment for all of my students, residents, and junior faculty. In addition, I have mentored undergraduates and high school students with a goal to enhance an early interest science and its application to healthcare. I have served as a mentor to over twenty students through Research Science Institute, Center for Excellence in Education. Additionally, I mentored several students through the CityLab at Boston University School of Medicine, a scientific training program for inner city high school students.

Embracing inclusion and promoting a diverse workforce is vital to strengthening biomedical research and advancing healthcare on local, national, and international levels. I recognize that DEIA work is an ongoing commitment, and I strive to continue supporting DEIA efforts within my own laboratory, at GSDM and Boston University.

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


Acting Chair
Boston University Henry M. Goldman School of Dental Medicine
Translational Dental Medicine


Research Assistant Professor
Boston University Chobanian & Avedisian School of Medicine
Biochemistry & Cell Biology


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


Associate Director for Basic Sciences
Boston University
BU-BMC Cancer Center


Member
Boston University
Evans Center for Interdisciplinary Biomedical Research


Member
Boston University
Genome Science Institute


Graduate Faculty (Primary Mentor of Grad Students)
Boston University Chobanian & Avedisian School of Medicine, Graduate Medical Sciences




Defining the Beta-catenin/CBP axis in head and neck cancer
12/07/2020 - 11/30/2025 (Multi-PI)
PI: Maria A. Kukuruzinska, PhD
NIH/National Institute of Dental & Craniofacial Research
5R01DE030350-03

Defining the impact of E7386 alone and in combination with anti-PD-1 antibody on tumor intrinsic immunity in head and neck cancer of the oral cavity
02/24/2022 - 02/24/2025 (PI)
Eisai, Inc.


Protocol # VIG-001, Clinical Evaluation of the OncAlert Rapid in Subjects Presenting for Evaluation and/or Initial Biopsy; Impact on Decision-Making.
12/18/2017 - 12/17/2021 (Multi-PI)
PI: Maria A. Kukuruzinska, PhD
Vigilant Biosciences, Inc.


Effects of E7386 monotherapy and combination therapies on head and neck cancer devleopment and progression in pre-clincial mouse models
06/06/2019 - 06/06/2020 (PI)
Eisai, Inc.


Repair, Regeneration and Fibrosis of the Salivary Gland
07/01/2015 - 06/30/2018 (PI)
NIH/National Institute of Dental & Craniofacial Research
5R21DE024954-02

Head and Neck Cancer Symposium: From Pathways to Therapies
08/01/2015 - 07/31/2016 (PI)
NIH/National Institute of Dental & Craniofacial Research
1R13DE025552-01

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 Foundation


Regulation of SMG Development by Adhesion Receptors
05/01/2002 - 04/30/2014 (PI)
NIH/National Institute of Dental & Craniofacial Research
5R01DE014437-08

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

Showing 10 of 12 results. Show All Results


Title


Yr Title Project-Sub Proj Pubs
2023 Defining the ß-catenin/CBP-catenin/CBP axis in head and neck cancer 5R01DE030350-03
2022 Defining the ß-catenin/CBP-catenin/CBP axis in head and neck cancer 5R01DE030350-02
2021 Enhancement and Cloud Deployment of CaDrA, a software tool for Candidate Driver Analysis of Multiomics Data 3R01DE030350-01A1S1
2021 Defining the ß-catenin/CBP-catenin/CBP axis in head and neck cancer 1R01DE030350-01A1
2016 Repair, Regeneration and Fibrosis of the Salivary Gland 5R21DE024954-02 1
2015 Head and Neck Cancer Symposium: From Pathways to Therapies 1R13DE025552-01
2015 Repair, Regeneration and Fibrosis of the Salivary Gland 1R21DE024954-01A1 1
2013 2013 Salivary Glands and Exocrine Biology Gordon Research Conference 1R13DE023467-01
2012 Regulation of SMG Development by Adhesion Receptors 5R01DE014437-08 5
2011 Regulation of SMG Development by Adhesion Receptors 5R01DE014437-07 5
Showing 10 of 62 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.

iCite Analysis       Copy PMIDs To Clipboard

  1. 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.View Related Profiles. PMID: 37353110
     
  2. 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.View Related Profiles. PMID: 36993637; PMCID: PMC10055367; DOI: 10.1101/2023.03.24.534064;
     
  3. 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.View Related Profiles. PMID: 35105672; PMCID: PMC9081163; DOI: 10.1158/1541-7786.MCR-21-0310;
     
  4. 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.View Related Profiles. PMID: 34045583; PMCID: PMC8159963; DOI: 10.1038/s41598-021-90569-w;
     
  5. 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; PMCID: PMC7801450; DOI: 10.1038/s41598-020-79650-y;
     
  6. 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.View Related Profiles. PMID: 32203567; PMCID: PMC7299767; DOI: 10.1039/d0mo00009d;
     
  7. 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.View Related Profiles. PMID: 30420594; PMCID: PMC6232154; DOI: 10.1038/s41368-018-0037-7;
     
  8. 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.View Related Profiles. PMID: 30029671; PMCID: PMC6053793; DOI: 10.1186/s13073-018-0569-7;
     
  9. 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
     
  10. 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.View Related Profiles. PMID: 29088714; PMCID: PMC5650269; DOI: 10.18632/oncotarget.19637;
     
Showing 10 of 148 results. Show More

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

Bar chart showing 148 publications over 37 distinct years, with a maximum of 10 publications in 1999

YearPublications
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Could Blocking Or Deleting A Protein Help Prevent Common Oral Cancers?

Medical Dialogues 6/2/2022

Could blocking or deleting a protein help prevent common oral cancers?

Medical Xpress 4/26/2022
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