Research Interests

Dr. Usatyuk’s investigations include work in the area of oxidative stress and role of oxidants in endothelial barrier function involving calcium signaling, cytoskeletal reorganization, focal adhesions and adherens junction proteins and protein tyrosine kinases. Additionally, current research includes hyperoxia-induced endothelial cell barrier function and cytoskeletal regulation of NADPH oxidase with the involvement of PLD/Rac1/IQGAP1 signaling pathway. The future studies will focus on the cytoskeleton regulation of caveolin-enriched microdomains (CEM) and CEM-mediated NADPH oxidase regulation and ROS production in endothelial cells to better understand the pathophysiology of vascular leak and lung injury.

• He D, Su Y, Usatyuk PV, Spannhake EW, Kogut P, Solway J, Natarajan V, Zhao Y. Lysophosphatidic acid enhances pulmonary epithelial barrier integrity and protects endotoxin-induced epithelial barrier disruption and lung injury. J Biol Chem. 2009. 284(36). - 24123-24132.
• Usatyuk PV, Gorshkova IA, He D, Zhao Y, Kalari SK, Garcia JGN, Natarajan V. Phospholipase D- Mediated Activation of IQGAP1 through Rac1 Regulates Hyperoxia-Induced p47phox Translocation and Reactive Oxygen Species Generation in Lung Endothelial Cells. J Biol Chem, 2009. 284, 22. – 15339-15352.
• Nagababu E, Usatyuk PV, Enika D, Natarajan V, Rifkind JM. Vascular Endothelial Barrier Dysfunction Mediated by Amyloid Proteins. J Alzheimer's Dis. 2009. 17. – 845-854.
• Pendyala S, Usatyuk PV, Gorshkova IA, Garcia GJN, Natarajan V. Regulation of NADPH Oxidase in Vascular Endothelium: The Role of Phospholipases, Protein Kinases, and Cytoskeletal Proteins. Antiox Redox Signal, 2009. (In press).
• Zhao Y, Usatyuk PV, Gorshkova IA, He D, Wang T, Moreno-Vinasco L, Geyh AS, Breysse PN, Samet JM Spannhake E, Garcia JGN, Natarajan V. Regulation of COX-2 Expression and IL-6 Release by Particulate Matter in Airway Epithelial Cells. Am J Respir Cell Mol Biol, 2009. 40(1):19-30.
• Pendyala S, Gorshkova IA, Usatyuk PV, He D, Pennathur A, Lambeth D, Tannickal VJ, Natarajan V. Role of NOX4 in Hyperoxia-induced Reactive Oxygen Species Generation and Migration of Human Lung Endothelial Cells. Antiox Redox Signal, 2009. 11:746-764.
• Chiang ET, Camp SM, Dudek SM, Brown ME, Usatyuk PV, Zaborina O, Alverdy JC, Garcia JGN. Protective Effects of High-Molecular Weight Polyethylene Glycol (PEG) in Human Lung Endothelial Cell Barrier Regulation: Role of Actin Cytoskeletal           Rearrangement. Microvascular Research. 2009. 77(2):174-86.
• Gorshkova I, He D.H., Berdyshev E, Usatuyk P, Burns M, Kalari S, Zhao Y, Pendyala S, Garcia J.G.N, Pyne N.J, Brindley D.N. and Natarajan V. Protein Kinase C-ε Regulates sphingosine 1-phosphate-mediated migration of human lung endothelial cells through activation of phospholipase D2, protein kinase C-ζ, and Rac1. J Biol Chem, 2008, 283(17):11794-06.
• Zhao Y, He D, Stern R, Usatyuk PV, Spannhake EW, Salgia R, Natarajan V. Lysophosphatidic acid modulates c-Met redistribution and hepatocyte growth factor/c-Met signaling in human bronchial epithelial cells through PKC delta and E-cadherin. Cell Signal. 2007;(11):2329-38.
• Usatyuk PV, Romer LH, He D.H., Parinandi NL, Kleinberg ME, Zhan S, Jacobson JR, Dudek S, Garcia JGN and Natarajan V. Regulation of Hyperoxia-induced NADPH Oxidase Activation in Human Lung Endothelial Cells by the Actin Cytoskeleton and Cortactin. J Biol Chem, 2007,282(32):23284-95.
• Dudek SM, Camp SM, Chiang ET, Singleton PA, Usatyuk PV, Zhao Y, Natarajan V, Garcia JG. Pulmonary endothelial cells barrier enhancement by FTY720 does not require the S1P(1) receptor. Cell Signal. 2007;(8):1754-64.
• Zhao Y, Kalari SK, Usatyuk PV,  Gorshkova IA, He DH, Watkins T, Brindley DN, Sun C, Bittman R, Garcia JG, Berdyshev EV, Natarajan V. Regulation of Intracellular Generation of Sphingosine-1-Phosphate by Lipid Phosphate Phosphatase-1 and Sphingosine kinase1 in Lung Endothelial Cells. J Biol Chem. 2007,11;282(19):14165-14177
• Georas SN, Berdyshev E, Hubbard W, Gorshkova IA, Usatyuk PV, Saatian B, Myers AC, Williams MA, Xiao HQ, Liu M, Natarajan V. Lysophosphatidic acid is detectable in human bronchoalveolar lavage fluids at baseline and increased after segmental allergen challenge. Clin Exp Allergy. 2007, 37(3):311-322.
• Zhu X, Learoyd J, Butt S,  Zhu L,  Usatyuk PV, Natarajan V, Munoz NM, Leff AR.Regulation of Eosinophil Adhesion by Lysophosphatidylcholine via a Non-store Operated Ca2+ Channel. Am J Respir Cell Mol Biol. 2007, 36(5):585-593.
• Usatyuk PV., Parinandi NL., Natarajan V. Redox Regulation of 4-HNE-mediated Endothelial Barrier Dysfunction by Focal Adhesion, Adherens and Tight Junction Proteins. J Biol Chem. 2006,281(46):35554-35566.
• Mirzapoiazova T., Kolosova I., Usatyuk P., Natarajan V, Verin A. Diverse effects of Vascular Endothelial Growth Factor on pulmonary endothelial barrier. Am J Physiol. 2006, 291(4):L718-724.
• Berdyshev EV, Gorshkova IA, Usatyuk PV, Zhao Y, Saatian B, Hubbard W, and Natarajan V. De Novo Biosynthesis of Dihydrosphingosine-1-Phosphate by Sphingosine Kinase 1 in Mammalian Cells. Cell Signal. 2006, 18(10):1779-1792
• Ye S.Q., Zhang L.Q., Adyshev D., Usatyuk P.V., Garcia A.N., Lavoie T.L., Verin A.D., Natarajan  V. and Garcia J.G.N. Pre-B-cell colony-enhancing factor is critically involved in thrombin-induced lung endothelial cell barrier dysregulation. Microvasc Res. 2005 Nov;70(3):142-51
• Usatyuk P.V., Natarajan V. Regulation of Reactive Oxygen Species-Induced Endothelial Cell-Cell and Cell-Matrix Contacts by Focal Adhesion Kinase and Adherens Junction Proteins. Am J Physiol. 2005, 289: L999-L1010.
• Birukova AA, Birukov KG, Adyshev D, Usatyuk P, Natarajan V, Garcia JG, Verin AD. Involvement of microtubules and Rho pathway in TGF-beta1-induced lung vascular barrier dysfunction. J Cell Physiol. 2005 Sep; 204(3):934-47
•  Kolosova I., Mirzapoiazova T., Adyshev D., Usatyuk P, Romer R, Jakobson J., Natarajan V.,. Garcia J. G. N. and Verin A. Mechanisms of ATP-induced endothelial cell barrier enhancement. / Circ Res. 2005 Jul 22;97(2):115-24.
• Chowdhury A.K., Watkins T., Parinandi N. L., Saatian B., Kleinberg M. A., Usatyuk P.V. and Natarajan V. Src Mediated Tyrosine Phosphorylation of  p47phox  in Hyperoxia-Induced Activation of NADPH Oxidase and Generation of Oxidants in Lung Endothelial Cells. /J Biol Chem – 2005, 280 (21):20700-20711
• Zhao Y., Usatyuk P.V., Cummings R., Saatian B., Morris A., Brindley D.N., Natarajan V. Role of lipid phosphate phosphatase in the regulation of lysophosphatidic acid-induced IL-8 secretion through calcium and NFkB in human bronchial epithelial cells. / Biochemical J. – 2005, 385(Pt 2): 493-502.
• Natarajan V., Usatyuk P.V. and Patterson C. E. Membrane and Cellular Signaling of Integrity and Acute Activation /In: “Advances in Molecular and Cell Biology”. - Hardbound, ISBN: 0-444-51834-7. – 2004, Vol. 35, Chapter 4. - 105-138.
• Ravi LB, Mohanty JG, Chrest FJ, Jayakumar R, Nagababu E, Usatyuk PV, Natarajan V, Rifkind JM. Influence of amyloid-beta fibrils on the interactions between red blood cells and endothelial cells/Neurological Research. -2004, 26(5): 579-585
• Usatyuk PV, Natarajan V. Role of Mitogen-Activated Protein Kinases in 4-Hydroxynonenal-Induced Actin Remodeling and Barrier Function in Endothelial Cells J Biol Chem. - 2004. – 279 (12):11789-11797.
• Birukova AA, Smurova K, Birukov KG, Usatyuk PV, Liu F, Kaibuchi K, Ricks-Cord A,  Natarajan V,  Alieva I, Garcia J GN, Verin A D. Microtubule disassembly induces cytoskeletal remodeling and lung vascular barrier dysfunction: role of Rho-dependent  mechanisms. J Cell Physiol. - 2004. -9999: 1-17.
• Usatyuk PV, Vepa S, Watkins T, He D.H, Parinandi N.L, Natarajan V. Redox Regulation of Reactive Oxygen Species-Induced p38 MAP Kinase Activation and Barrier Dysfunction in Lung Microvascular Endothelial Cells. Antiox Redox Signal 2003, 5(6). - 723-730.
• Usatyuk PV., Fomin V, Shu Shi, J. G. Garcia, K. Schaphorst, V.  Natarajan. Role of Ca2+ in diperoxovanadate-induced cytoskeletal rearrangement and barrier function in endothelial cell. Am J Physiol 2003. -285(1): L1006-1017.
• N.L.Parinandi, M.A.Kleinberg, P.V.Usatyuk, R.J.Cummings, Pennathur, A.J.Cardounel, J.L.Zweier, J. G. Garcia, V.  Natarajan. Hyperoxia-induced NAD[P]H oxidase activation and regulation by MAP kinases in human lung endothelial cells. Am J Physiol.- 2003,  284(1): L26-38.
• R.J.Cummings, N.L.Parinandi, A. Zaiman, L.Wang, P.V.Usatyuk, J. G. Garcia, V.  Natarajan. Phospholipase D activation by Sphingosine-1-Phosphate regulates interleukin-8-secretion in human bronchial epithelial cells. J Biol Chem.-2002, 277(33). - 30227-35.
• Lixin Wang, R.J.Cummings, P.V.Usatyuk, A.Morris, K.Irani, V.  Natarajan. Involvement of phospholipase D1 and D2 in sphingosine 1-phosphate-induced ERK activation and interleukin-8 secretion in human bronchial epithelial cells. Biochem J. - 2002, 367(3):751-760.
• R.J.Cummings, N.L.Parinandi, Lixin Wang, P.V.Usatyuk, V.  Natarajan. Phospholipase D/phosphatidic acid signal transduction: role and physiological significance in lung. Mol Cell Biochem. - 2002, 234-235 (1-2): 99-109.
• Usatiuk PV, Tsvilikhovsky MI, Aniiefiok A, Mel’nychuk DO. Dynamics of blood proteins spectra in normal and diarrheic newborn cattle during early ontogenesis. Fiziol Zh. - 2001. -47(6) 0:58-62 Ukrainian.
• Mel'nichuk DO, Tsvilikhovskii NI, Lyubetskaya TV, Usatiuk PV, Tomchuk VA, Yakimchuk OM. New evidence for the mechanism(s) of the colostrum immunity formation in new born calves and its significance for practice in veterinary medicine. Manual for milk farms of Ukraine. – 2001.-Kiev, National Agrarian University Print Center. – P.12 .
• Mel'nichuk DO., Tsvilikhovskii NI, Usatiuk PV, Zakharenko NA. Biochemistry of membrane digestion and metabolic processes in the tissues of new born calves at norm and under pathology. Nauk Visn Nat Agr Univ. 2000 (1): 31-38. Ukrainian.
• Tsvilikhovskii NI, Tomchuk VA, Yakimchuk OM, Usatiuk P.V, Mel'nichuk DO.  Action of  feeding components on functional activity of plasma membrane proteins of small intestine enterocytes. Nauk Visn Nat Agr Univ. 2000 (24): 10-18. Ukrainian.
• Usatiuk PV. Methodical aspects of obtaining isolated small intestine epithelial cells. Ukr Biokhim Zh. 1999 Mar-Apr; 71(2): Review. Ukrainian.
• Mel'nichuk DA, Usatiuk PV, Tsvilikhovsky MI. Biochemical mechanism of diarrhea development in newborn calves. Vet Med Ukr. 1999 January; 32-33. Ukrainian.
• Mel'nichuk DA, Usatiuk PV. The role of plasma membrane proteins of small intestine epithelium in colostral immunity formation of new born calves. Nauk Visn Nat Agr Univ. 1998 (6): 13-20. Ukrainian.
• Usatiuk PV, Melnychuk D.O. Preparation of apical and basolateral membranes from small intestinal epithelium. Methodologic aspects. Ukr Biokhim Zh. 1995 Sep-Oct; 67(5): 16-24. Review. Ukrainian. PMID: 8830431; UI: 96167758.
• Mel'nichuk DA, Tereshchenko MP, Tsvilikhovskii NI, Usatiuk PV. Protein differences of two parts of cattle epithelium plasma membrane. Dokl Nat Acad Sci Ukr. l995 (9): 104-106. Ukrainian.
• Usatiuk PV, Tomchuk VA, Mel'nichuk DO. Content of prostaglandins E2 and Fla in small intestine epithelium of cattle as a function of age and pathology in non-infectious diarrhea. Ukr Biokhim Zh. 1995 Mar-Apr; 67(2): 106-8. Ukrainian. PMID: 8592776; UI: 96060209.
• Tomchuk VA, Usatiuk PV, Tsvilikhovskii NI, Mel'nichuk DO. The obtaining of isolated epithelial cells from the small intestine of cattle. Fiziol Zh. 1994 Sep-Dec; 40(5-6): 45-51. Ukrainian. PMID: 8521990; UI: 96059891.
• Mel'nichuk DA, Aniefiok Ayaya, Usatiuk PV. The postnatal features of protein contents from blood plasma of cattle. Dokl Nat Acad Sci Ukr. 1992(8): 152-155. Ukrainian.
• Mel'nichuk DA. Usatiuk PV, Tomchuk VA. Carbohydrate and energetic exchange in the isolated small intestine cells of cattle at different age and under pathology. Dokl Nat Acad Sci Ukr.1991.137-140. Russian
• Usatiuk P.V, Tsvilikhovskii NI, Mel'nichuk DO. The age-related characteristics of the transport ATPase activity in the enterocyte plasma membranes of the small intestine. Biull Eksp Biol Med. 1991 Mar; 11, 1(3): 309-11. English. PMID: 1647236; Ul: 91274697. (Consultants Bureau, New York, USA).
• Usatiuk PV, Volkov GL, Tsvilikhovskii NI, Mel'nichuk DA.  Plasma membranes lipid composition of jejunum enterocytes in cattle of different age. Ukr Biokhim Zh. 1990 May-Jun; 62(3): 87-94. Russian. PMID: 2396325; UI: 90371652. English. (Allerton Press, N.Y.,USA)
• Usatiuk PV, Tsvilikhovskii NI, Mel'nichuk DO. Adenosine triphosphatases from plasma membranes of cattle intestinal epithelium. Biokhimiia. 1990; 55(4): 712-7. English. (Plenum Publishing Corporation).
• Mel'nichuk DA,Usatiuk PV, Tsvilikhovskii NI. Changes in the activity of alkaline phosphatase and Na K - ATPase in the membrane fractions of small-intestinal epithelium in the normal state and in diarrhea. Fhiziol Zh. 1989 May-Jun; 35(3): 99-102. Russian. PMID: 2544466; UI: 89290086.
• Tsvilikhovskii NI,Usatiuk PV, Mel'nichuk DO.  Isolation, purification and characteristics of brush border and basolateral membranes from cattle intestinal epithelium cells. Ukr Biokhim Zh. 1988 Nov-Dec; 60(6): 91-4. Russian. PMID: 2853473; UI: 89188067.
• Tugai VA, Dyadyusha GP, Usatyuk PV, Zemlyanaya NN. Influence of monovalent cation gradients on active Ca2+  transport in the sarcoplasmic reticulum and proteoliposomes. Ukr Biokhim Zh. 1988 Jan-Feb; 60( 1 ):69-74. PMID: 3363678; UI: 88205734. English. (Allerton Press, N.Y.,USA)
• Mel'nichuk DA, Zasekin DA, Zakharenko NA, Mel’nikova NN, Tishchenko GN, Shabelnik NM, Usatyuk PV.  Characteristics of blood electrolyte balance in newborn calves under normal conditions and in diarrhea. Ukr Biochim Zh. 1987 Vol. 59, No 6: 59-63 English. (Allerton Press, N.Y.,USA)
• Kurskii MD, Tugai VA, Usatyuk PV. Changes in intravesicular pH during Ca2+ transport in the sarcoplasmic reticulum. Ukr Biokhim Zh. 1986 Jan-Feb; 5 8(1): 56-62. Russian. PMID: 3946018; UI: 86124183.
• Usatiuk PV, Tugai VA. Changes in the intensity of the fluorescence of potential-sensitive fluorescent probes in the active transport of Ca2+ in the fragmented sarcoplasmic reticulum. Biofizika. 1985 May-Jun; 30(3): 450-4. Russian. PMID: 4027274; UI: 85280577.
• Tugai VA, Voizitskii VM, Kurskii MD, Kucherenko NE, Usatiuk PV. Membrane potential during Ca++ transport and AMP deamination in vesicles of the sarcoplasmic reticulum. Ukr Biokhim Zh. 1983 Jan-Feb; 55(l): 58-63. Russian. PMID: 6829080; UI: 83147397.
• Tugai VA, Usatiuk PV, Kurskii MD. Interaction of fluorescent probes with membranes of sarcoplasmic reticulum in AMP deamination. Ukr Biokhim Zh. 1982; 54(1): 61-5. Russian. PMID: 7058553; UI: 82130315.
• Kurskii MD, Tugai VA, Usatiuk PV, Didina SE. Effect of ammonium ions on calcium release from fragmented sarcoplasmic reticulum. Ukr Biochim Zh. 1980 Nov-Dec: 52(6): 737-41. PMID: 6789525
• Tugai VA, Usatiuk PV. Simultaneous recording of Ca2+ and pH when studying the processes of calcium transport in sarcoplasmic reticulum. Ukr Biokhim Zh. 1979 Sep-0ct; 51(5): 508-10. Russian. PMID: 42178; UI: 80082687.