Dr. John Kolega Pathology And Anatomical Sciences Department of Pathology & Anatomical Sciences 206A Farber Hall 3435 Main Street Buffalo NY, 14214 Phone: (716) 829-3527 Fax: (716) 829-2911 Email: kolega@buffalo.edu View map

OFFICE LOCATIONS

Dept. of Pathology & Anatomical Sciences 206A Farber Hall State University of New York at Buffalo 3435 Main Street Buffalo NY, 14214 Phone: 716 829-3527 Fax: 716 829-2911 Email: kolega@buffalo.edu View map

DESCRIPTION OF INTERESTS

My primary research interest is the behavior of endothelial cells, which form the inner lining of blood vessels and are key players in the remodeling events that occur during wound healing, aneurysm formation, tumor growth, and a wide variety of disease conditions. There are two questions about endothelial behavior that drive most of the research in my laboratory: (1) How does an endothelial cell migrate during wound healing and blood-vessel remodeling? We are particularly interested in the motor protein, myosin II, and how it exerts force within the cytoskeleton to push or pull the cell as it moves. In order to study the organization and movements of cytoskeletal proteins - and not just there biochemical properties - we use a variety of light microscopic methods to examine the dynamics and biochemistry of cytoskeletal proteins in living migrating endothelial cells. We also use conventional biochemical, genetic, and pharmacological manipulations to investigate the regulatory events that control myosin II behavior in situ. (2) How do endothelial cells sense and respond to their mechanical environment? Blood vessels remodel to accommodate long-term changes in blood flow. Certain flow environments can cause destructive remodeling that leads to cerebral aneurysms (local “ballooning” of vessels). Working with biomedical engineers in the laboratory of Dr. Hui Meng at the Toshiba Stroke Research Center, we use cell culture and whole animal systems to examine how endothelial cells respond to specific hemodynamic micro-environments in order to understand the mechanism and regulation of flow-induced remodeling, especially as it relates to cerebral aneurysms. A third interest is understanding the response of cultured endothelial cells to electrical fields, which have been shown to orient endothelial migration in vitro and to suppress edema in vivo by enhancing the endothelial permeability barrier.

SPECIALTIES

Cardiovascular Disease Cytoskeleton and cell motility Molecular and Cellular Biology

EDUCATION

1984	Doctor of Philosophy, Cell Biology Yale University
1981	Master of Philosophy, Biology Yale University
1978	Bachelor of Arts, Life Sciences Massachusetts Institute of Technology
1978	Bachelor of Science, Chemistry Massachusetts Institute of Technology

EXPERTISE

Cell Biology Cytoskeletal regulation and mechanism in cell migration. Endothelial cell biology.

Cell Biology Cytoskeleton and Cell Motility

Gross Anatomy back and extremeties

Vascular Biology endothelial signaling, vessel wall remodeling

PUBLICATIONS

Ionita CN, Paciorek AM, Hoffmann KR, Bednarek DR, Yamamoto J, Kolega J, Levy EI, Hopkins LN, Rudin S, Mocco J, Kolega JP; Asymmetric vascular stent: feasibility study of a new low-porosity patch-containing stent.; Stroke; 2008 Jul; 39(7); 2105-2113

Szymanski MICHAEL, Metaxa E, Meng H, Kolega J, Kolega JP; Endothelial Cell Layer Subjected to Impinging Flow Mimicking the Apex of an Arterial Bifurcation.; Ann Biomed Eng; 2008 Jul;

Gao L, Hoi Y, Swartz DD, Kolega J, Siddiqui A, Meng H, Kolega JP; Nascent aneurysm formation at the basilar terminus induced by hemodynamics.; Stroke; 2008 Jul; 39(7); 2085-2090

Metaxa E, Meng H, Kaluvala SR, Szymanski MP, Paluch RA, Kolega J, Kolega JP; Nitric oxide-dependent stimulation of endothelial cell proliferation by sustained high flow.; Am J Physiol Heart Circ Physiol; 2008 Jun;

Meng H, Wang Z, Hoi Y, Gao L, Metaxa E, Swartz DD, Kolega J, Kolega JP; Complex hemodynamics at the apex of an arterial bifurcation induces vascular remodeling resembling cerebral aneurysm initiation.; Stroke; 2007 Jun; 38(6); 1924-1931

Meng H, Swartz DD, Wang Z, Hoi Y, Kolega J, Metaxa EM, Szymanski MP, Yamamoto J, Sauvageau E, Levy EI, Kolega JP; A model system for mapping vascular responses to complex hemodynamics at arterial bifurcations in vivo.; Neurosurgery; 2006 Nov; 59(5); 1094-1100

Kolega J, Kolega JP; The role of myosin II motor activity in distributing myosin asymmetrically and coupling protrusive activity to cell translocation.; Mol Biol Cell; 2006 Oct; 17(10); 4435-4445

Martins GG, Kolega J, Kolega JP; Endothelial cell protrusion and migration in three-dimensional collagen matrices.; Cell Motil Cytoskeleton; 2006 Feb; 63(2); 101-115

Kolega J; Phototoxicity and photoinactivation of blebbistatin in UV and visible light.; Biochem Biophys Res Commun; 2004 Jul; 320(3); 1020-1025

Kolega J; Asymmetric distribution of myosin IIB in migrating endothelial cells is regulated by a rho-dependent kinase and contributes to tail retraction.; Mol Biol Cell; 2003 Dec; 14(12); 4745-4757

KOLEGA J Li X; Effects of direct current electric fields on cell migration and actin filament distribution in bovine vascular endothelial cells; Journal of Vascular Research; 2002; 39; 4745-4757

John Kolega; Turnover rates at regulatory phosphorylation sites on myosin II in endothelial cells.; J Cell Biochem; 1999 Dec; 75(4); 629-639

K. Hahn, John Kolega, J. Montibeller, R. DeBiasio, P. Post, J. Myers, D. L. Taylor; Fluorescent analogs: optical biosensors of the chemical and molecular dynamics of macromolecules in living cells.; Fluorescent and Luminescent Probes for Biological activity: A Practical Guide to Technology for Quantitative Real-Time Analysis (W.T. Mason, ed.); 1999 Jan;

John Kolega; Cytoplasmic dynamics of myosin IIA and IIB: spatial ‘sorting‘ of isoforms in locomoting cells.; J Cell Sci; 1998 Aug; 111 (; 2085-2095

John Kolega; Fluorescent analogues of myosin II for tracking the behavior of different myosin isoforms in living cells.; J Cell Biochem; 1998 Mar; 68(3); 389-401

John Kolega; Asymmetry in the distribution of free versus cytoskeletal myosin II in locomoting microcapillary endothelial cells.; Exp Cell Res; 1997 Feb; 231(1); 66-82

Taylor DL, DeBiasio R, LaRocca G, Pane D, Post P, John Kolega, Giuliano K, Burton K, Gough B, Dow A; Potential of machine-vision light microscopy in toxicologic pathology.; Toxicol Pathol; 1994; 22(2); 145-159

John Kolega, Taylor DL; Gradients in the concentration and assembly of myosin II in living fibroblasts during locomotion and fiber transport.; Mol Biol Cell; 1993 Aug; 4(8); 819-836

John Kolega, Nederlof, M. A., Taylor, D. L.; Quantitation of cytoskeletal fibers in fluorescence images: stress fiber disassembly accompanies dephosphorylation of the regulatory light chains of myosin II.; Bioimaging; 1993 Jan; 1; 136-150

Giuliano KA, John Kolega, DeBiasio RL, Taylor DL; Myosin II phosphorylation and the dynamics of stress fibers in serum-deprived and stimulated fibroblasts.; Mol Biol Cell; 1992 Sep; 3(9); 1037-1048

Loomis CA, John Kolega, Manabe M, Sun TT; Characterization of a keratinocyte-specific extracellular epitope of desmoglein. Implications for desmoglein heterogeneity and function.; J Biol Chem; 1992 Aug; 267(23); 16676-16684

Janson LW, John Kolega, Taylor DL; Modulation of contraction by gelation/solation in a reconstituted motile model.; J Cell Biol; 1991 Sep; 114(5); 1005-1015

John Kolega, Janson LW, Taylor DL; The role of solation-contraction coupling in regulating stress fiber dynamics in nonmuscle cells.; J Cell Biol; 1991 Sep; 114(5); 993-1003

John Kolega, Taylor, D. L.; Regulation of actin and myosin II dymamics in living cells.; Ordering the Membrane-Cytoskeleton Trilayer (J.S. Morrow and M.S. Mooseker, eds.); 1991 Jan;

John Kolega, Manabe M; Tissue-specific distribution of a novel component of epithelial basement membranes.; Exp Cell Res; 1990 Aug; 189(2); 213-221

John Kolega, Manabe M, Sun TT; Basement membrane heterogeneity and variation in corneal epithelial differentiation.; Differentiation; 1989 Oct; 42(1); 54-63

John Kolega; Effects of mechanical tension on protrusive activity and microfilament and intermediate filament organization in an epidermal epithelium moving in culture.; J Cell Biol; 1986 Apr; 102(4); 1400-1411

John Kolega; The cellular basis of epithelial morphogenesis.; Developemtnal Biology: An Ongoing Synthesis (L.W. Browder, ed.); 1986 Jan; 2; 103-143

John Kolega, Shure MS, Chen WT, Young ND; Rapid cellular translocation is related to close contacts formed between various cultured cells and their substrata.; J Cell Sci; 1982 Apr; 54; 23-34

John Kolega; The movement of cell clusters in vitro: morphology and directionality.; J Cell Sci; 1981 Jun; 49; 15-32