Education & Training
- Ph.D. in Biology from Massachusetts Institute of Technology, 2005
- B.S. in Biology from Cornell University, 1996
Research Interest Summary
The proper organization of cell-cell contacts is required for tissue formation and function in multicellular organisms. At cell-cell contacts, specialized protein complexes link opposing cell membranes to physically couple cells. The cadherin-catenin complex, the core component of the adherens junction, links the actin cytoskeleton to the plasma membrane to provide structural integrity and mechanical strength to the cell-cell contact. Disruptions in cadherin-catenin function are linked to a range of human disorders and diseases, from cardiomyopathies to cancer metastasis. However, cytoskeletal architecture at cell-cell contacts remains poorly defined, and cadherin-catenin functions in regulating cytoskeletal organization are not well understood.
The long-term objective of our work is to gain a deep mechanistic understanding of cadherin-catenin functions in cytoskeleton organization and cell-cell adhesion. Current research in the Kwiatkowski seeks to: 1) Define cadherin-catenin functions in cardiomyocyte adhesion and intercalated disc organization, and 2) Determine how the cadherin-catenin complex regulates cell-cell adhesion to guide neural tube morphogenesis. We use a combination of biochemistry, cell biology, super resolution microscopy and developmental biology to study cadherin and catenin functions at the molecular, cellular and organismal levels using primary cultured cells, mice and zebrafish as models.
Kwiatkowski AV*, Rubinson DA*, Dent EW, van Veen JE, Leslie JD, Zhang J, Mebane LM, Philippar U, Pinheiro EM, Burds AA, Bronson RT, Mori S, Fässler R, Gertler FB. Ena/VASP is required for neuritogenesis in the developing cortex. Neuron. 2007 Nov 8;56(3):441-455. PMID: 17988629
Furman C, Sieminski AL, Kwiatkowski AV, Rubinson DA, Vasile E, Bronson RT, Fässler R, Gertler FB. Ena/VASP is required for endothelial barrier function in vivo. J Cell Biol. 2007 Nov 19;179(4):761-775. PMID: 17998398
Dent EW, Kwiatkowski AV, Mebane L, Philippar U, Barzik M, Rubinson DA, Furman C, Burds AA, Alberts AS, Gertler FB. Filopodia are required for cortical neurite formation. Nat Cell Biol. 2007 Dec; 9(12):1347-1359. PMID: 18026093
Kwiatkowski AV, Garner CG, Nelson WJ, Gertler FB. Cell autonomous defects in cortical development revealed by two-color chimera analysis. Mol Cell Neurosci 2009 May;41(4):44 –50. PMID: 19386231
Benjamin JM*, Kwiatkowski AV*, Yang C, Korobova F, Pokutta S, Svitkina T, Weis WI, Nelson WJ. AlphaE-Catenin regulates actin dynamics independently of cadherin-mediated cell-cell adhesion. J Cell Biol. 2010 Apr 19;189(2):339-352. PMID: 20404114
Kwiatkowski AV*, Maiden SL*, Pokutta S, Choi HJ, Nelson WJ, Weis WI, Hardin J. In vitro and in vivo reconstitution of the cadherin-catenin-actin complex from Caenorhabditis elegans. Proc Natl Acad Sci USA. 2010 Aug 17;107(33):14591-14596. PMID: 20689042
Miller PW, Pokutta S, Ghosh A, Almo SC, Weis WI, Nelson WJ, Kwiatkowski AV. Danio rerio αE-catenin is a monomeric F-actin binding protein with distinct properties from Mus musculus αE-catenin. J Biol Chem. 2013 Aug 2;288(31):22324-22332. PMID: 23788645
Hansen SD*, Kwiatkowski AV*, Ouyang C, Liu H, Pokutta S, Volkmann N, Hanein D, Weis WI, Mullins RD, Nelson WJ. Alpha-catenin actin binding domain alters actin filament conformation and regulates binding of nucleation and disassembly factors. Mol Biol Cell. Dec;24(23):3710-20. PMID: 24068324