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Institute of Molecular Medicine

Laboratory of Andrei Ivanov, Ph.D.

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Research projects

Dr. Ivanov’s laboratory studies mechanisms that regulate structure and functions of epithelial apical junctions. Apical junctions are the most recognizable morphological entities of different epithelia that mediate tissue integrity and barrier properties as well as epithelial cell differentiation and motility.

Dr. Ivanov’s research has two major directions that are funded by two NIH RO1 grants. One direction is to dissect the roles of vesicle exocytosis in biogenesis and dysfunctions of epithelial junctions during mucosal inflammation and tumor progression. Current projects focus on the involvement of different SNARE proteins as well as a key SNARE adaptor, aSNAP, in assembly and maintenance of epithelial junctions. These studies have been recently expanded to dissect the roles of aSNAP in apoptosis, autophagy and cell-matrix adhesions. Dr. Ivanov is collaborating with Dr. Paul B. Fisher in studying mechanisms of epithelial cell apoptosis.

The other direction of Dr. Ivanov’s laboratory is to elucidate molecular mechanism by which the cellular cytoskeleton regulates epithelial junctions. Specifically, Dr. Ivanov targets the roles of different actin isoforms as well as proteins that regulate F-actin turnover such as cofilin, ADF, WDR1, LIM kinase and Arp2/3 complex. Previous studies from Dr. Ivanov’s lab have established a key role of the non-muscle myosin II motor in regulating the dynamics of epithelial junctions in vitro. These studies have been expanded in vivo by creating a conditional knockout of myosin IIA isoform in the intestinal epithelium. This project is a collaborative effort between Dr. Ivanov and Dr. Robert Adelstein from NIH and it will address involvement of myosin II in the development of intestinal inflammation and colon cancer.

From the translational perspectives, Dr. Ivanov’s work is aimed to develop novel strategies to prevent breakdown of epithelial barriers and accelerate their recovery during mucosal damage and restitution. Another translational goal is to inhibit disruption of cell-cell junctions during cancer cell dissemination, which is a promising therapeutic approach to prevent tumor metastasis.

Laboratory members

Susana Lechuga, Ph.D.
Postdoctoral Fellow

Nayden G. Naydenov, Ph.
Instructor

Dongdong Wang, Ph.D.
Postdoctoral Fellow

Key publications

Baranwal S, Naydenov NG, Harris G, Dugina V, Morgan K, Champonnier C and Ivanov AI. Non-redundant roles for cytoplasmic b- and g-actin isoforms in regulation of epithelial junctions. Mol Biol Cell (in press).

Naydenov NG, Brown B, Harris G, Dohn MR, Morales VM, Reynolds AB and Ivanov AI. A membrane fusion protein aSNAP is a novel regulator of epithelial apical junctions. PLoS One 7: e343320, 2012.

Naydenov NG, Harris G, Brown B, Schaefer KL, Das SK, Fisher PB and Ivanov AI. Loss of aSNAP induces epithelial cell apoptosis via downregulation of Bcl-2 expression and disruption of the Golgi. J Biol Chem 2012,287: 5928-5941.

Rezaeel F, Emo JA, Meedhu N, Saatian B, Chapman TJ, Naydenov NG, DeBenedetto A, Beck LA, Ivanov AI, and Georas SN. PolyI:C induces protein kinase D-dependent disassembly of apical junctions and barrier dysfunction in airway epithelial cells. J Allergy Clin Immunol 2011, 128: 1216-1224.

Naydenov NG and Ivanov AI. Adducins regulate remodeling of apical junctions in human epithelia. Mol Biol Cell 2010, 21: 3506-3517.

Naydenov NG, Hopkins AM and Ivanov AI. c-Jun N-terminal kinase mediates disassembly of apical junctions in model intestinal epithelia. Cell Cycle 2009, 8: 2110-2121.

Ivanov AI, Young S, Den Beste K, Capaldo C, Humbert PO, Brennwald P, Parkos CA and Nusrat A. Tumor suppressor Scribble regulates assembly of tight junctions in the intestinal epithelium. Am J Pathol2010, 176: 134-145.

Ivanov AI, Parkos CA and Nusrat A. Cytoskeletal regulation of epithelial barrier function during inflammation. Am J Path 2010, 177: 512-524.

Babbin BA, Koch S, Bachar M, Conti M-A, Parkos CA, Adelstein RS, Nusrat A, and Ivanov AI. Non-muscle myosin IIA differentially regulates intestinal epithelial cell restitution and matrix invasion. Am J Pathol 2009, 174: 436-448.

Ivanov AI. Pharmacological inhibitors of different endocytic pathways: are they specific enough to be useful? Methods Mol Biol2008, 440: 15-33.

Ivanov AI, Hopkins AM, Brown GT, Gerner-Smidt K, Babbin BA, Parkos CA and Nusrat A. Myosin II regulates the shape of three-dimensional epithelial cysts. J Cell Sci 2008, 121: 1803-1814.

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