Tatiana V Byzova Ph.D.

Staff

  • Department of Molecular Cardiology
  • Lerner Research Institute / NB50
  • 9500 Euclid Avenue
  • Cleveland, Ohio 44195
  • byzovat@ccf.org
  • (216) 445-4312
  • (216) 444-9263

The major objective of my research program is to fully integrate the mechanistic studies performed at the molecular and cellular levels with complex in vivo models of human diseases to yield a complete understanding of fundamental problems in physiology and pathophysiology. The major research focus of the lab is on the mechanisms governing the pathological and adaptive vasculature development, neoangiogenesis, in adult organisms. This process is crucial for the tissue recovery from ischemia, a response that is triggered in a variety of pathogenic settings including the complications of thrombosis, injury and wound healing, and cancer progression and tumor metastatic spread. At the cellular level, we are interested in endothelial cell biology, the role of inflammatory and other blood cells, including platelets, during neovascularization. To consider neoangiogenesis at a molecular level, my research has emphasized the regulatory functions of extracellular matrix, its cellular receptors, integrins and signaling pathways and the interrelationship between these processes. For our angiogenesis studies, we employ cutting edge animal models, including angiogenesis induced by various tumors, by ischemic conditions in hind limbs, wounds and skin transplants, and by gene transfer of the growth factor of interest. We have established a number of other valuable in vivo models that include wound healing, tumor progression, metastasis and tumor-induced bone remodeling in transgenic/knockout mice, angiogenesis and blood flow analysis, atherosclerosis and thrombosis models.

CLEVELAND CLINIC COLLABORATORS

Jihad Kaouk, M.D., Urology
Eric Klein, M.D., Urology                                                   
Brian Rini, M.D., Solid Tumor Oncology
Andrew Stephenson, M.D., Urology

In other words ...

The Byzova Lab's aim is to understand how blood vessels function in adulthood and development, how normal and healthy vasculature is preserved, and what methods control vascular growth in adults.

  • Bethany Kerr Ph.D.
  • Project Staff
  • Location:NB5-69
  • Phone:(216) 445-8237
  • kerrb2@ccf.org
  • Young-Woong Kim Ph.D.
  • Postdoctoral Fellow
  • Location:NB5-107
  • Phone:(216) 445-8237
  • kimy3@ccf.org
  • Julia Meller Ph.D.
  • Postdoctoral Fellow
  • Location:NB5-107
  • Phone:(216) 445-8237
  • mellerj@ccf.org
  • Miroslava Tischenko B.A.
  • Senior Research Technologist
  • Location:NB5-107
  • Phone:(216) 444-8179
  • tischem@ccf.org
  • Valentin Yakubenko Ph.D.
  • Staff Scientist
  • Location:NB5-48
  • Phone:(216) 445-8211
  • Fax:(216) 445-8204
  • yakubv@ccf.org

HIGHLIGHTED PUBLICATIONS

  1. Kim Y and Byzova TV. “Oxidative stress in angiogenesis and vascular disease.” Blood (2013): in press.
  2. Kerr BA, ...Byzova TV. “Interference with Akt signaling protects against myocardial infarction and death by limiting the consequences of oxidative stress.” Science Signaling (2013): 6(287):ra67.
  3. Zhao Y, ...Byzova TV. “Regulation of cell adhesion and migration by Kindlin-3 cleavage by calpain.” JBiolChem (2012): 287(47):40012-20.
  4. West XZ, and Malinin NL, ..., Byzova TV. “Oxidative stress induces angiogenesis by activating TLR2 with novel endogenous ligands.” Nature 467(7318) (2010): 972-976.
  5. Malinin NL, ...Shurin SB, Plow EF, Byzova TV. “A point mutation in KINDLIN-3 ablates activation of three integrin subfamilies in humans.” Nature Medicine 15(3) (2009): 313-318.
  6. Chen J, and Somanath PR, ..., Byzova TV. “Akt1 regulates pathological angiogenesis, vascular maturation and permeability in vivo.” Nature Medicine 11(11) (2005): 1188-1196.

ADDITIONAL PUBLICATIONS

  1. Kerr BA, McCabe NP, Feng W, Byzova TV. “Platelets govern pre-metastatic tumor communication to bone.” Oncogene (2013): 32(36):4319-24.
  2. Kim Y, West XZ, Byzova TV. “Inflammation and oxidative stress in angiogenesis and vascular disease.” Journal of Molecular Medicine (2013): 91(3):323-8.
  3. Panigrahi S, Ma Y, Hong L, Gao D, West XZ, Salomon RG, Byzova TV, Podrez EA. “Engagement of Platelet Toll-Like Receptor 9 by Novel Endogenous Ligands Promotes Platelet Hyper-Reactivity and Thrombosis.” Circulation Research (2012): 112(1):103-12.
  4. Ding L,Biswas S, Morton RE, Smith JD, Hay N, Byzova TV, Febbraio M, Podrez EA. “Akt3 deficiency in macrophages promotes foam cell formation and atherosclerosis in mice.” Cell Metabolism (2012): 15(6):861-72.
  5. Goc A, Liu J, Byzova TV, Somanath PR. “Akt 1 mediates prostate cancer cell microinvasion and chemotaxis to metastatic stimuli via integrin β(3) affinity modulation.” British Journal of Cancer (2012): Aug 7;107(4):713-23.
  6. Kerr BA and Byzova TV, “The dark side of the oxidative force in angiogenesis.” Nature Medicine (2012): 18(8):1184-5.
  7. Meller J, Malinin NL, Panigrahi S, Kerr BA, Patil A, Ma Y, Venkateswaran L, Rogozin IB, Mohandas N, Ehlayel M, Podrez EA, Chinen J, Byzova TV, “Novel aspects of Kindlin-3 function in humans based on a new case of LAD-III deficiency.” Journal of Thrombosis and Haemostasis, (2012): 10(7):1397-408.
  8. Malinin NL, Pluskota E, Byzova TV, “Integrin signaling in vascular function.” Current Opinion in Hematology, 19(3) (2012): 206-11.
  9. West XZ, Meller N, Malinin NL, DeshmukhL, MellerJ, Mahabeleshwar GH, WeberME, KerrBA, Vinogradova O, Byzova TV, “Integrin β3 crosstalk with VEGFR accommodating tyrosine phosphorylation as a regulatory switch.” PLoS One, 7(2) (2012): e31071.
  10. Murphy EA, Zarpellon A, Hofmann JJ, Merkulova A, Shields DJ, Weis SM, Byzova TV, Ruggeri ZM, Iruela-Arispe ML, Cheresh DA, “Notch promotes vascular maturation by inducing integrin-mediated smooth muscle cell adhesion to the endothelial basement membrane.” Blood, 119(9) (2012):2149-58.
  11. Malinin NL, and West XZ, Byzova TV, “Oxidation as ‘the stress of life.’ ” Aging3(9)(2011): 906-10.
  12. Deshmukh L, and Meller N, Alder N, Byzova T, Vinogradova O. “Tyrosine phosphorylation as a conformational switch: A case study of integrin Beta3 cytoplasmic tail.” J Biol Chem. 286(47) (2011): 40943-53.
  13. Pluskota E, and JJ Dowling, N Gordon, JA Golden, D Szpak, XZ West, C Nestor, YQ Ma, K Bialkowska, TV Byzova, EF Plow. “The integrin co-activator Kindlin-2 plays a critical role in angiogenesis in mice and zebrafish.” Blood 117(18) (2011):4978-4987.
  14. Feng W, and M Madajka, BA Kerr, GH Mahabeleshwar, SW Whiteheart, TV Byzova. “A novel role for platelet secretion in angiogenesis: Mediating bone marrow-derived cell mobilization and homing.” Blood 117(14) (2011): 3893-3902. Editorial and cover.
  15. Goc A, and M Chaudhary, TV Byzova, SR Somanath. “TGFβ- and bleomycin-induced extracellular matrix synthesis is mediated through Akt and mammalian target of rapamycin (mTOR).” Journal of Cell Physiology 226(11) (2011): 3004-13
  16. McCabe, NP, and BA Kerr, M Madajka,A Vasanji, TV Byzova. “Augmented osteolysis in SPARC deficient mice with bone residing prostate cancer.” Neoplasia 13(1) (2011): 31-39.
  17. Somanth PR, and EA Podrez, J Chen, Y Ma, K Marchant, M Antoch, TV Byzova. “Deficiency in core circadian protein Bmal1 is associated with a prothrombotic and vascular phenotype.” Journal of Cellular Physiology 226(1)(2011): 132-140.
  18. Bledzka K, and K Bialkowska, H Nie, J Qin, TV Byzova, C Wu, EF Plow, YQ Ma. “Tyrosine phosphorylation of {beta}3 integrin regulates kindlin-2 binding and integrin activation.” Journal of Biological Chemistry 285(40) (2010): 30370-30374.
  19. Bialkowska, K, and YQ Ma, K Bledzka, K Sossey-Alaoui, L Izem, X Zhang, NL Malinin, J Qin, TV Byzova, EF Plow. “The integrin co-activator kindlin-3 is expressed and functional in a non-hematopoietic cell, the endothelial cell.” Journal of Biological Chemistry 285(24) (2010): 18640-18649.
  20. Kerr, BA, and TV Byzova. “Integrin Alpha V.” UCSD-Nature Molecule Pages (2010): Epub.
  21. Malinin, NL, and EF Plow, TV Byzova. “Kindlins in FERM adhesion.” Blood 115(20) (2010): 4011-4017.
  22. Kerr, BA, and R Miocinovic, AKSmith, EA Klein, TV Byzova. “Comparison of tumor and microenvironment secretomes in plasma and in platelets during prostate cancer growth in a xenograft model.” Neoplasia 12(5) (2010): 388-396.
  23. Kerr, BA, and TV Byzova. “αβ-Crystallin: a novel VEGF chaperone.” Blood 115(16) (2010): 3181-3183.
  24. Ren, B, and Y Deng, A Mukhopadhyay, AA Lanahan, ZW Zhuang, KL Moodie, MJ Mulligan-Kehoe, TV Byzova, RT Peterson, M Simons. “ERK1/2-Akt1 crosstalk regulates arteriogenesis in mice and zebrafish.” Journal of Clinical Investigation 120(4) (2010): 1217-1228.
  25. Plow EF, Ma YQ, TV Byzova, Q Jun. “Platelet Aggregation: A Brief Historical and Molecular Perspective.” Journal of Thrombosis and Thrombolysis 26(1) (2009): 68-70
  26. Plow, EF, and J Qin, TV Byzova. “Kindling the flame of integrin activation and function with kindlins.” Current Option in Hematology 16(5) (2009): 323-328.
  27. Somanath, PR, and J Vijai, JV Kichina, TV Byzova, ES Kandel. “The role of PAK-1 in activation of MAP kinase cascade and oncogenic transformation by Akt.” Oncogene 28(25) (2009): 2365-2369.
  28. Somanath, PR, and NL Malinin, TV Byzova. “Cooperation between integrin aVb3 and VEGFR2 in angiogenesis.” Angiogenesis 12(2) (2009): 177-185.
  29. Malinin, NL, and L Zhang, J Choi, A Ciocea, OV Razorenova, Y Ma, EA Podrez, M Tosi, DP Lennon, AI Caplan, SB Shurin, EF Plow, TV Byzova. “A point mutation in KINDLIN-3 ablates activation of three integrin subfamilies in humans.” Nature Medicine 15(3) (2009): 313-318. Comment in Nature Medicine 15(3) (2009): 249-250. Comment in Science-Business eXchange at nature.com.
  30. Somanath, PR, and A Ciocea, TV Byzova. “Integrin and Growth Factor Receptor Alliance in Angiogenesis.” Cell Biochemistry and Biophysics 53(2) (2009): 53-64.
  31. Somanath, PR, and TV Byzova.“14-3-3β-Rac1-p21 activated kinase signaling regulates Akt1 mediated cytoskeletal organization, lamellipodia formation and fibronectin matrix assembly.” Journal of Cellular Physiology 218(2) (2009): 394-404.
  32. Feng, W, and NP McCabe, GH Mahabeleshwar, PR Somanath, DR Phillips, TV Byzova. “The angiogenic response is dictated by β3 integrin on bone marrow-derived cells.” Journal of Cell Biology183(6) (2008): 1145-1157.
  33. Malinin, NL, and TV Byzova. “CD40/TRAF6 switch in neointimal hyperplasia.” Blood 111(9) (May 1, 2008): 4424. Comment in Blood 111(9) (2008): 4596-4604.
  34. Mahabaleshwar, GH, and TV Byzova. “Vascular integrin signaling.” Methods of Enzymology 443 (2008): 199-226.
  35. Valiyaveettil, M, and N Kar, MZ Ashraf, TV Byzova, M Febbraio, EA Podrez. “Oxidized high-density lipoprotein inhibits platelet activation and aggregation via scavenger receptor BI.” Blood 111(4) (2008): 1962-1971.
  36. Mahabeleshwar, GH, and J Chen, W Feng, PR Somanath, OV Razorenova, TV Byzova. “Integrin affinity modulation in angiogenesis.” Cell Cycle 7(3) (2008): 335-347.
  37. Somanath, PR, and J Chen, TV Byzova. “Akt1 is necessary for the vascular maturation and angiogenesis during cutaneous wound healing.” Angiogenesis 11(3) (2008): 277-288.
  38. McCabe, NP, and M Madajka, A Vasanij, TV Byzova. “Intraosseous injection of RM1 murine prostate cancer cells promotes rapid osteolysis and periosteal bone deposition.” Clinical & Experimental Metastasis 25(5) (2008): 581-590.
  39. Mahabaleshwar, GH, and TV Byzova. “Angiogenesis in melanoma.” Seminars in Oncology 34(6) (2007): 555-565.
  40. Mahabeleshwar, GH, and W Feng, K Reddy, EF Plow, TV Byzova. “Mechanisms of integrin-VEGF receptor cross-activation in angiogenesis.” Circulation Research 101(6) (2007): 570-580. Comment in Circulation Research 101(6) (2007): 536-538.
  41. McCabe, NP, and S De, A Vasanji, J Brainard, TV Byzova. “Prostate cancer specific integrin aVb3 modulates bone metastatic growth and tissue remodeling.” Oncogene 26(42) (2007): 6238-6243.
  42. Podrez. EA, and TV Byzova, M Febbraio, RG Salomon, Y Ma, M Valiyaveettil, E Poliakov, M Sun, PJ Finton, BR Curtis, J Chen, R Zhang, RL Silverstein, SL Hazen. “Platelet CD36 links hyperlipidemia, oxidant stress and a prothrombotic phenotype.” Nature Medicine 13 (9) (Sep. 2007): 1086-1095. Comment in Nature Medicine 13(9) (2007): 1015-1016.
  43. Somanath, PR, and ES Kandel, WS Chen, N Hay, TV Byzova. “Akt1 signaling regulates integrin activation, matrix recognition and fibronectin assembly.” Journal of Biological Chemistry 282(31) (2007): 22964-22976.
  44. Mahabeleshwar, GH, and W Feng, DR Phillips, TV Byzova. “Integrin signaling is critical for pathological angiogenesis.” Journal of Experimental Medicine 203(11) (2006): 2495-2507.
  45. Byzova, TV. “Matrix rules: key role for microfibrillar protein in vascular development.” Blood 107(11) (2006): 4202-4203.
  46. Mahabaleshwar, GH, and PR Somanath, TV Byzova. “Methods for isolation of endothelial and smooth muscle cells and in vitro proliferation assays.” Methods in Molecular Medicine 129 (2006): 197-208.
  47. Somanath, PR, and OV Razorenova, J Chen, TV Byzova. “Akt1 in endothelial cells and angiogenesis.” Cell Cycle 5(5) (2006): 512-518.
  48. Chen, J, and PR Somanath, OV Razorenova, P Bornstein, WS Chen, N Hay, TV Byzova. “Akt1 regulates pathological angiogenesis, vascular maturation and permeability in vivo.” Nature Medicine11(11) (2005): 1188-1196.
  49. Narizhneva, NV, and OV Razorenova, EA Podrez, J Chen, UM Chandraesekharan, PEDiCorleto, EF Plow, EJ Topol, TV Byzova.“Thrombospondin-1 up-regulates expression of cell adhesion molecules and promotes monocyte binding to endothelium.” FASEB Journal 19(9) (2005): 1158-1160.
  50. De, S, and OV Razorenova, NP McCabe, T O’Toole, J Qin, TV Byzova. “VEGF–Integrin interplay controls tumor growth and vascularization.” Proc. Natl. Acad. Sci.102(21)(2005): 7589-7594.
  51. Dreicer, R, and P Elson, D Peereboom, TV Byzova, EF Plow, EA Klein. “Phase II trial of GM-CSF + thalidomide in patients with androgen-independent metastatic prostate cancer.” Urologic Oncology 23(2) (2005): 82-86.
  52. Byzova, TV. “Integrins in bone recognition and metastasis.” Journal of Musculoskeletal and Neuronal Interactions 4(4) (2004): 374.
  53. Chen, J, and S De, D Damron, WS Chen, N Hay, TV Byzova. “Impaired platelet response to thrombin and collagen in AKT-1 deficient mice.” Blood 104(6) (2004):1703-1710.
  54. Stenina, OI, and TV Byzova, JC Adams, EJ Topol, EF Plow. “Cardiovascular disease and the thrombospondin single nucleotide polymorphisms.” International Journal of Biochemistry and Cell Biology 36(6) (2004): 1013-1030.
  55. Narizhneva, NV, and VJ Byers-Ward, MJ Quinn, FJ Zidar, EF Plow, EJ Topol, TV Byzova. “Molecular and functional differences induced in thrombospondin-1 by the single nucleotide polymorphism associated with the risk of premature, familial myocardial infarction.” Journal of Biological Chemistry 279(20) (2004): 21651-21657.
  56. Chen, J, and S De, NV Narijneva, TV Byzova. “Migratory responses of metastatic prostate cancer are controlled by VEGF.” Cell Communication and Adhesion 11(1) (2004): 1-12 (cover page).
  57. De, S, and J Chen, NVNarijneva, J Brainard, W Heston, EH Sage, TV Byzova. “Molecular pathway for prostate cancer metastasis to bone.” Journal of Biological Chemistry 278(4) (2003): 39044-39050.
  58. Quinn, MJ, and TV Byzova, J Qin, EJ Topol, EF Plow. “Integrin {α}IIb{β}3 and its antagonism.” Arteriosclerosis, Thrombosis, and Vascular Biology 23(6) (2003): 945-952.
  59. Mazurov, AV, and DV Pevzner, OA Antonova, TV Byzova, SG Khaspekova, AV Semenov, TN Vlasik, AN Samko, II Staroverov, MY Ruda. “Safety, inhibition of platelet aggregation and pharmacokinetics of F(ab')2 fragments of the anti-glycoprotein IIb-IIIa monoclonal antibody in high-risk coronary angioplasty. Platelets 13(8) (2002): 465-477.
  60. Plow, EF, and TA Haas, TV Byzova. “Platelet receptors: fibrinogen.” Platelets in Thrombotic and Non-Thrombotic Disorders. Cambridge, UK, Cambridge University Press, 2002.Ch. 13, 188-195.
  61. Byzova, TV, and CK Goldman, J Chen, G Cabrera, MG Achen, M Seminaow, SR Deitcher, PE DiCorleto. “Adenovirus encoding VEGF-D induces tissue-specific vascular patterns in vivo. Blood 99(12) (2002): 4434-4442.
  62. Mazurov, AV, and DV Pevzner, SG Khaspekova, OA Dudnik, TV Byzova, TN Vlasik, VN Bakharev, MI Pistsov, II Staroverov, MI Ruda. “Inhibition of thrombocyte aggregation by F(ab')2-fragments of monoclonal antibodies FraMon (CRC64) to glycoproteins IIb-IIIa.” Ter Arkh 73(9) (2001): 66-73.
  63. Plow, EF, and CS Cierniewski, Z Xiao, TA Haas, TV Byzova. “aIIbb3 and its antagonism at the new millennium.” Thrombosis and Haemostasis 86(1) (2001): 34-40.
  64. Byzova, TV, and CK Goldman, N Pampori, KA Thomas, A Bett, SJ Shattil, EF Plow. “A mechanism for modulation of cellular responses to VEGF: activation of the integrins.” Molecular Cell 6(4) (2000): 1-10.
  65. Byzova, TV, and EF Plow. “The PlA2 allele and cardiovascular disease: the pro33 and con.” Journal of Clinical Investigation 105(6) (2000): 697-698.
  66. Byzova, TV, and W Kim, RJ Midura, EF Plow. “Activation of integrin αvβ3 regulates cell adhesion and migration to bone sialoprotein.” Experimental Cell Research 254(2) (2000): 299-308.
  67. Plow, EF, and TV Byzova. “Prothrombin as a ligand for aIIbb3 and aVb3 defines new paradigms in the recognition specificity of b3 integrins.” New Frontier in Vascular Biology: Thrombosis and Hemostasis (1999): 65-75.
  68. Plow, EF, and TV Byzova. “The biology of glycoprotein IIb-IIIa.” Journal of Coronary Artery Disease 10(8) (1999): 547-553.
  69. Cierniewski, CS, and TV Byzova, M Papierak, T Haas, J Niewiarovska, L Zhang, M Cieslak, EF Plow. “Peptide ligands can bind to distinct sites in integrin aIIbb3 and elicit different functional responses.” Journal of Biological Chemistry 274(24) (1999): 16923-16932.
  70. Topol, EJ, and TV Byzova, EF Plow. “Of platelets, integrin aIIbb3 and GPIIb-IIIa blockers: past, present and future perspectives.” Lancet353(9148) (1999): 227-231.
  71. Byzova, TV, and EF Plow. “Activation of aVb3 on vascular cells controls recognition of prothrombin.” Journal of Cell Biology143(7)(1998): 2081-2092.
  72. Byzova, TV, and R Rabbani, SD Souza, EF Plow. “Role of integrin aVb3 in vascular biology.” Thrombosis and Haemostasis80(5) (1998): 726-734.
  73. Byzova, TV, and EF Plow. “Networking in the hemostatic system: integrin aIIbb3 binds prothrombin and influence its activation.” Journal of Biological Chemistry 272(43) (1997): 27183-27188.
  74. Mazurov, AV, and SG Khaspekova, TV Byzova, OY Tikhomirov, MC Berndt, B Steiner, WC Kouns. “Stimulation of platelet glycoprotein IIb-IIIa (α IIb β 3-integrin) functional activity by a monoclonal antibody to the N-terminal region of glycoprotein IIIa.” FEBS Letters 391(1-2) (1996): 84-88.
  75. Khaspekova, SG, and TV Byzova, OY Tikhomirov, MC Berndt, WC Kouns and AV Mazurov. “Conformational changes in platelet glycoprotein IIb-IIIa (α IIb β 3-integrin) stimulated by a monoclonal antibody to the N-terminal region of glycoprotein IIIa.” Biochemistry(Moscow) 61(3) (1996): 305-317.
  76. Byzova, TV, and YA Romanov, TN Vlasik, AV Mazurov. “Interaction of monoclonal antibody against P-selectin with activated platelets and endothelial cells. Heterogeneity of P-selectin expression in endothelial cells from human aorta.” Biochemistry(Moscow) 60(8) (1995): 218-235.
  77. Bochkov, VN, and EV Sorokin, TV Byzova, AV Mazurov, P Little, A Bobik, VA Tkachuk. “Do glycoproteins IIb/IIIa participate in activation of human platelets by low density lipoproteins?Biochemistry (Moscow) 60(8) (1995): 1187-1194.
  78. Romanov, YA, and IV Balyasnikova, VB Bystrevskaya, TV Byzova, OP Ilyinskaya, AV Krushinsky, RV Latsis, EL Soboleva, EM Tararak, VN Smirnov. “Endothelial heterogeneity and intimal blood born cells: relation to human atherosclerosis.” Ann. New York Academy of Science 748 (1995): 12-37.
  79. Byzova, TV, and TN Vlasik, AV Mazurov. “Inhibition of platelet aggregation by monoclonal antibody against glycoprotein IIb-IIIa complex.” Bull. Exp. Biol. Med. 118(10) (1994): 402-405.
  80. Khaspekova, SG, and TN Vlasik, TV Byzova, DV Vinogradov, MC Berndt, AV Mazurov. “Detection of an epitope specific for the dissociated form of glycoprotein IIIa of platelet membrane glycoprotein IIb-IIIa complex and its expression on the surface of adherent platelets.” British Journal of Haematology 85(2) (1993): 332-340.

ABSTRACTS (selected from more than 150):

  1. BA Kerr, L Ma, XZ West, NL Malinin, ME Weber, L Ding, EA Podrez, TV Byzova.  “Akt1 Deletion Promotes Survival in a Model of Spontaneous Myocardial Infarction and Atherosclerosis.”  Atherosclerosis, Thrombosis, and Vascular Biology Scientific Sessions, Chicago, IL, 2012.
  2. XZ West, NL Malinin, BA Kerr, EA Podrez, RG Saloman, TV Byzova.  “Oxidized phospholipid metabolites as a novel class of TLR2 ligands.”  Keystone Symposia on Angiogenesis: Advances in Baseic Science and Therapeutic Applications, Snowbird, UT, 2012.
  3. Y Zhao, I Rogozin, TV Byzova.  “Model-based phylogenomics of cell adhesion machinery in metazoans.”  Cleveland Clinic 31st Annual Research Day, Cleveland, OH, 2011.
  4. BA Kerr, W Feng, M Madajka, NP McCabe, TV Byzova.  “Platelets Transport the Tumr Secretome during Cancer Progression and Metastasis.”  XXIII Congress of the International Society on Thrombosis and Haemostatis, Kyoto, Japan, 2011.
  5. BA Kerr, M Ranko, AK Smith, XZ West, DE Hansel, WD Heston, EA Klein, J Kaouk, TV Byzova.  “CD117 Expression in Circulating Cells as Potential Predictor of Advanced Prostate Cancer.”  11th Annual Meeting of the Society of Urologic Oncology, Bethesda, MD, 2011.
  6. XZ West, NL Malinin, BA Kerr, EA Podrez, RG Salomon, TV Byzova. “Oxidation-Associated Molecular Patterns in Inflammation and Angiogenesis.”  5th Cleveland State Interdisciplinary Research Conference, Cleveland, OH, 2011.  Winner of 1st place graduate poster.
  7. BA Kerr, and W Feng, NP McCabe, TV Byzova.  “Platelet Alpha-Granules Sequester and Release the Tumor Secretome.”  Gordon Research Conference on Cell Biology of Megakaryocytes and Platelets, Galveston, TX, 2011.
  8. XZ West, NL Malinin, AA Merkulova, M Tischenko, BA Kerr, EA Podrez, RG Salomon, and TV Byzova.  “Oxidized phospholipid metabolites as a novel class of TLR2 ligands.”  Gordon Research Conference on Vascular Cell Biology, Ventura, CA, 2011.
  9. J Meller and TV Byzova.  “Kindlins 2 and 3 play distinct roles in inside out integrin activation in migrating endothelial cells.”  Gordon Research Conference on Vascular Cell Biology, Ventura, CA, 2011.
  10. AK Smith, TV Byzova,W Heston, and EA Klein.  “Role of circulating neoplastic progenitor cells in detection and staging of prostate cancer.”  2010 American Urological Association Annual Meeting, San Francisco, CA, 2010.
  11. BA Kerr, R Miocinovic, AKSmith, EA Klein, and TV Byzova. “Platelets as carriers of tumor and microenvironment secretomes during prostate cancer growth.” Platelets International Symposium, Jerusalem, Israel, 2010.
  12. TV Byzova, NL Malinin, J Choi, A Ciocea, L Zhang, EA Podrez, M Tosi, DP Lennon, A Caplan, EF Plow, and SP Shurin.  “Kindlin3 in integrin activation.”  22nd Congress of the International Society of Thrombosis and Haemostasis, Boston, MA, 2009.
  13. W Fengand TV Byzova. "Integrin function on bone marrow derived cells.” Keystone Symposium on angiogenesis, Vancouver, British Columbia, 2008.
  14. NP McCabe, M Madajka, A Vasanji, and TV Byzova. “Role of tumor integrins in bone lesion development,” presented at Skeletal Complications of Malignancy V Symposium, Philadelphia, PA, 2007.
  15. PR Somanath, J Chen, and TV Byzova. “Akt1 dictates the balance between VEGF and PDGF signaling during cutaneous wound healing,” presented at the Lerner Research Institute Staff Retreat, Cleveland Clinic Foundation, Cleveland, OH, 2007. Winner of Best Poster Award.
  16. PR Somanath, J Chen, and TV Byzova. “Protein Kinase Ba (Akt1)-mediated extra-cellular matrix remodeling is essential for vascular responses,” presented at the Circulation Research 4th Annual meeting of BVCS, American Heart Association, Keystone, CO, Aug. 1, 2007. Winner of New investigator travel award.  Published in Circulation Research 101(5) (Aug. 31, 2007): ePub.
  17. PR Somanath, ES Kandel, W Chen, N Hay, and TV Byzova. “Akt1 regulate integrin activation and fibronectin assembly,” presented at the 26th Annual Research day, Cleveland Clinic Foundation, Cleveland, OH, 2006.
  18. A Ciocea, TV Byzova,and M Kalafatis. “Role of casein kinase 2 in platelets release from megakaryocytes,” presented at the 47th Annual Meeting, American Society of Hematology, Orlando, FL, 2006.
  19. P McCabe, S De, A Vasanji, J Brainard, and TV Byzova.“The functional state of integrin avb3 governs skeletal growth of prostate cancer,” presented at the Edward A. Smuckler Memorial Workshop, Pathobiology of Cancer, Snowmass Village, CO, 2006.
  20. PR Somanath, ES Kandel, W Chen, N Hay, and TV Byzova. “Akt1 regulates integrin activation, extracellular matrix recognition and fibronectin assembly,” presented at the 11th Biennial Midwest Platelet Conference, Chicago, IL, 2006.
  21. W Feng, GH Mahabeleshwar, DR Phillips, and TV Byzova. “The role of beta3 phosphorylation in angiogenesis and tumor growth,” presented at the 11th Biennial Midwest Platelet Conference, Chicago, IL, 2006.
  22. GH Mahabaleshwar, W Feng, and TV Byzova. “Integrins and extracellular matrix in angiogenesis,” presented at the Midwest Platelet Conference, Chicago, IL, 2006.
  23. GH Mahabaleshwar, W Feng, DR Phillips, and TV Byzova. “Integrin signaling is critical for pathological angiogenesis,” presented at the 26th Annual Research day, Cleveland Clinic Foundation, Cleveland, OH, 2006. Abstract # 141.
  24. TV Byzova, J Chen, and PR Somanath. “Akt pathway and extracellular matrix control tumor growth in vivo,” presented at the 11th World Congress on Advances in Oncology and 9th International Symposium on Molecular Medicine, Crete, Greece, 2006.
  25. PR Somanath, ES Kandel, and TV Byzova. “Akt1 regulates integrin activation matrix recognition and fibronectin assembly,” presented at the Lerner Research Institute-Research Retreat, Cleveland Clinic Foundation, Cleveland, OH, 2005. Winner of Best Abstract Award.
  26. PR Somanath, ES Kandel, W Chen, N Hay, and TV Byzova. “Akt1 regulates integrin activation, matrix recognition and assembly,” presented at the Lerner Research Institute-Research Retreat, Cleveland Clinic Foundation, Cleveland, OH, 2005.
  27. NP McCabe and TV Byzova. “Direct intra-bone injection of TRAMP cells as a model to investigate the role of SPARC in prostate cancer growth in bone,” presented at Prostate Cancer: Road Map to the Future, Niagara Falls, NY, 2005.
  28. GH Mahabaleshwar and TV Byzova. “Role of beta 3 integrin and its phosphorylation in vascular biology,” presented at the 47th Annual Meeting, American Society of Hematology, Atlanta, GA, 2005.
  29. GH Mahabaleshwar, W Feng, and TV Byzova. “Beta 3 integrin phosphorylation controls control pathological angiogenesis in vivo,” presented at the Special Conference on “Anti-Angiogenesis and drug delivery to tumors,” AACR, Waltham, MA, 2005, B38.
  30. S De, NP McCabe, OV Razorenova, and TV Byzova. “VEGF and beta 3 integrin control tumor growth within the bone and tumor vascularization,” presented at the Special Conference on “Anti-Angiogenesis and drug delivery to tumors,” AACR, Waltham, MA, 2005, B39.
  31. OV Razorenova, A Ivanov, A Budanov, TV Byzova, and P Chumakov. “Development of readout system for monitoring HIF-1 transcriptional activity,” FASEB Journal 18(8) (2004): B526.
  32. TV Byzova, J Chen, and PR Somanath. “Akt1 regulates angiogenesis in skin,” presented at the 46th Annual Meeting, American Society of Hematology, San Diego, CA, 2004.
  33. NV Narijneva, OV Razorenova, EA Podrez, EJ Topol, and TV Byzova. “Thrombospondin-1 induces expression of cell adhesion molecules and monocyte adhesion via IAP,” presented at the Midwest Platelet Conference, 2004.
  34. J Chen, PR Somanath and TV Byzova. “Akt1 in Angiogenic responses,” presented at the Midwest Platelet Conference, 2004.
  35. J Chen, S De, OV Razorenova, NVNarijneva, EA Podrez and TV Byzova. “Akt-1 regulates beta 3 integrin activation,” Atherosclerosis, Thrombosis and Vascular Biology Conference, American Heart Association, 2004.
  36. TV Byzova.Mechanism of prostate cancer metastasis,” presented at theInternational Hermelin Brain Tumor Symposium on matricellular proteins in normal and cancer cell-matrix interactions, Detroit, MI, 2004.
  37. S De and TV Byzova.  “Recognition of bone matrix proteins by activated integrins,” presented at the 43rd Annual Meeting of American Society of Cell Biology, Cleveland Clinic Foundation, Cleveland, OH, 2003.
  38. NV Narijneva, EJ Topol and TV Byzova. “Thrombospondin-1 and functional consequences of its polymorphisms,” presented at the Late Breaking News Session, American Heart Association, 2002.
  39. NV Narijneva, EJ Topol and TV Byzova. “Thrombospondin-1 and its polymorphisms,” presented at the Midwest Platelet Conference, 2002.
  40. NV Narijneva and TV Byzova. “TSP-1 and functional consequences of its polymorphisms,” presented at the 22nd Annual Research Day, Cleveland Clinic Foundation, Cleveland, OH, 2002. Winner of the Bumpus Award in Basic Science.
  41. J Chen and TV Byzova. “Integrin activation is a critical event in bone metastasis,” presented at the 22nd Annual Research Day, Cleveland Clinic Foundation, Cleveland, OH, 2002. Winner of the Bumpus Award in Basic Science.
  42. TV Byzova, EV Negresku, and EF Plow. “Differential effect of GPIIb-IIIa blockers on platelet mediated thrombin generation,” presented at the XVIII Congress of the International Society on Thrombosis and Hemostasis, 2001.
  43. AV Mazurov, DV Pevzner, SG Khaspekova, TV Byzova, OA Dudnik, OA Antonova, VN Bakharev, TN Vlasik, II Staroverov, MY Ruda, VN Smirnov, and EI Chazov.  “Inhibition of platelet aggregation by Fab2 fragments of a mutine monoclonal antibogy Framon against GPIIb-IIIa in healthy volunteers and patients undergoing high-risk angioplasty,” presented at the XVIII Congress of the International Society on Thrombosis and Hemostasis, 2001.
  44. TV Byzova et al. “VEGFR2-mediated cellular responses,” presented at the XVIII Congress of the International Society on Thrombosis and Hemostasis, 2001.
  45. TV Byzova. “Integrin activation is a critical event in cellular responses to VEGF,” presented at the Keystone Conference on Angiogenesis and Related Diseases, Alberta, Canada, 2001.
  46. TV Byzova, CK Goldman,N Pampori, SJ Shattil, and EF Plow. “Direct communication between growth factors and integrins,” AHA, Circulation, 2000.
  47. TV Byzova and EF Plow. “The angiogenic response: communication between growth factors and integrins,” presented at the 41st Annual Meeting of American Society of Hematology, New Orleans, LA, 1999.  Blood 94(10) (1999): 1.
  48. TV Byzova, WE Kim and EF Plow. “Acceleration of prothrombin activation by its interaction with aIIbb3,” presented at the XVII Congress of the International Society on Thrombosis and Hemostasis, Thrombosis and Haemostasis, Washington, DC, 1999, 78(1): pg. 410, #1301.
  49. TV Byzova and EF Plow. “Control of vascular cell functions by the activation states of integrin αVβ3,” presented at the 40th Annual Meeting of American Society of Hematology, Miami, FL, 1998.  Blood 92(10) (1998): 549a, #2257.
  50. TV Byzova and EF Plow. “Of αβaVb3 and its ligand repertoire,” presented at the Midwest platelet Conference, Memphis, TN, 1998.
  51. TV Byzova and EF Plow. “Prothrombin and b3 integrins as a receptor-ligand paradigm,” presented at the 18th Annual Research Day, Cleveland Clinic Foundation, Cleveland, OH, 1998, abstract #111.
  52. EF Plow and TV Byzova. “Glycoprotein IIb-IIIa: a multifaceted platelet integrin,” presented at Congress of International Society of Hematology (ISH-EHA), Amsterdam, The Netherlands, 1998.
  53. TV Byzova and EF Plow. “aVb3 function on vascular cells,” presented at the Meeting of American Society of Cell Biology, Washington, DC, 1997.
  54. TV Byzova and EF Plow. “Novel mechanism for controlling thrombin generation,” presented at the17th Annual Research Day, Cleveland Clinic Foundation, Cleveland, OH, 1997, abstract #121.
  55. TV Byzova and EF Plow. “Interaction of prothrombin with activated aVb3 on vascular cells,” presented at the 39th Annual Meeting of American Society of Hematology, Miami, FL, 1997. Blood 90 (1997): 1259.

Search PubMed for articles by Dr. Byzova

US Patent Patent Title Issue Date First-Named Inventor
8,080,252 Compounds and Methods of Modulating Angiogenesis 12/20/2011 Tatiana V. Byzova, Ph.D.
[Pending] Use of Platelets As a Source of Prostate Cancer Biomarkers Tatiana V. Byzova, Ph.D.

PERSONAL STATEMENT

Dr. Byzova’s research program is focused on the mechanisms governing the pathological and adaptive vasculature development in adult organisms. Dr. Byzova was trained as a fellow by Dr. Edward Plow, Department Chair of Molecular Cardiology at Cleveland Clinic, who is a key authority in integrin signaling in vascular biology and hemostasis. As a faculty member at Cleveland Clinic, Dr. Byzova learned not only how to carry out rigorous science, but also how to ensure that her projects are clinically important. Dr. Byzova’s lab strives to apply mechanistically oriented research to solve existing problems in patients care as well as to find new interesting directions in translational and clinical research. Their studies are focused on vasculature development, recruitment of inflammatory cells, interactions between growing vasculature and circulating blood cells (including platelets), the role of oxidative processes in regulation of vasculature. They incorporate state-of-the-art animal models of human diseases, including various models of ischemic injury, myocardial infarction, thrombosis, and angiogenesis. Mechanistically, Dr. Byzova’s lab focuses on the role of integrin and integrin-dependent complexes in basic cell migration, endothelial biology and angiogenesis. In their studies on integrin signaling they have identified a new player, Kindlin (Malinin et al., Nature Medicine), which is involved in integrin activation on numerous cell type including endothelium. Besides their interest in the mechanisms and role of integrins in VEGF-driven vascularization, Dr. Byzova’s lab is interested in novel VEGF independent mechanisms of vascularization. They have recently shown that the end products of lipid oxidation are generated during inflammation, and accumulate in wounds, in areas of myocardial infarction and in aging and are able to trigger angiogenesis via TLR2 receptors (West et al., Nature). This distinct pathway also leads to integrin activation and engagement. Thus, in their studies on the role of integrins, they consider both activators of endothelial function, VEGFR2 and TLR2.

ABOUT THE BYZOVA LAB MEMBERS

Dr. Bethany Kerr (Project Staff) has been a valuable member of the Byzova lab since 2008. Her broad expertise in bone biology, stem cell biology, thrombosis, and haemostasis allows her to pursue her goal of developing a translational research program that draws upon her basic science research aimed at elucidating the mechanisms of communication between a growing primary tumor and the bone microenvironment prior to metastasis and uses these identified mechanisms to discover biomarkers of prostate cancer patient progression and recurrence. Dr. Kerr currently collaborates closely with Cleveland Clinic’s Glickman Urological and Kidney Institute to examine platelet sequestered proteins and circulating progenitor cell populations in prostate cancer and renal cell carcinoma patients with the aim of finding markers to identify cancer patients with advanced disease and those likely to experience recurrence. The results of Dr. Kerr’s research have resulted in several highly-praised publications, ‘Platelets Govern Pre-Metastatic Tumor Communication to Bone’ (Kerr BA, et al., Oncogene, 2013) and ‘Comparison of Tumor and Microenvironment Secretomes in Plasma and in Platelets during Prostate Cancer Growth in a Xenograft Model.’ (Kerr BA, et al., Neoplasia, 2010). Dr. Kerr’s main goal is to improve our understanding of prostate cancer metastasis and develop strategies to monitor patients for advanced disease and recurrence.

To learn more about Dr. Kerr and her cutting-edge research, please see her personal website (coming soon): https://sites.google.com/site/bethanykerrlab/

Dr. Youngwoong Kim (Postdoctoral Research Fellow) joined the Byzova Lab in 2011 as a Postdoctoral Fellow. His current interests are inflammation and gene-targeted mouse generation and analysis. His current project is elucidating the clearance mechanism of one of the lipid end-products. The results of his research have been accepted by the scientific community in his publication entitled ‘Defective Notch activation in microenvironment leads to myeloproliferative disease’ (Kim YW et al., Blood, 2008), which was highlighted in the ‘Signaling’ section of Nature Reviews Cancer (http://www.nature.com/nrc/ journal/v8/n11/full/nrc2538.html). He has a background in molecular biology, mouse genetics, and immunology, having earned his B.S. and Ph.D. from Pohang University of Science and Technology in South Korea.

Dr. Julia Meller (Postdoctoral Research Fellow) joined the Byzova Lab in 2009 after completing her doctoral training with Dr. Martin Schwartz, a distinguished scientist in the field of integrins. The discovery of Kindlins as direct mediators of integrin activation by the Byzova Lab triggered her interest in the field of integrin activation. Her studies involving LADIII patient samples led her to discover novel phenotypical features of Kindlin 3 deficiency. During her subsequent work with an animal model of LADIII, she found a novel role of K3 in the function of microglia cells, leading to her publication entitled ‘Novel aspects of Kindlin-3 function in humans based on a new case of Leukocyte Adhesion Deficiency III (LAD-III)’ (Meller J et al., Journal of Thrombosis and Heamostasis, 2012). Her current project is focused on elucidating the role of Kindlin 3 in the integrin mediated modulation of neural circuits by microglia cells. Dr. Meller has a background in cell biology, signal transduction, and integran activation, having earned her B.S. and M.S. from Ben Gurion University in Isreal, and her Ph.D. from University of Virginia in Charlottesville, Virginia.

Mira Tischenko (Senior Research Technologist) has been with the Byzova Lab since 2010. Her many contributions to the lab’s studies on cellular and molecular mechanisms of angiogenesis include: development of techniques and experiments, establishment of professional connections and collaborations, cancer research/tumor growth, histopathology, preparation of samples and analysis including organ collection and dissection, molecular biology and microscopy, in vitro and in vivo experiments, cell culture, pre-clinical research such as animal work with mice, blood sample collection and analysis, drug delivery and testing, and ongoing research in cardiovascular diseases and angiogenesis. Ms. Tischenko was heavily involved in the design and implementation of the department’s Vasculata Conference 2009 Workshop, a national educational course offered as an introduction to vascular biology. Ms. Tischenko received her B.A. in Molecular Biology from Zhitomir Medical College in the Ukraine, and her B.A. in Business Administration from Tiffin University in Tiffin, Ohio.

PROJECT HIGHLIGHTS


Illustration by David Schumick/CCF

Tumor growth requires additional blood vessel growth or angiogenesis. We have found that platelets are required for tumor angiogenesis. Platelets control blood vessel growth (red cells by stimulating bone marrow-derived cell recruitment to tumors (green cells). Feng W … TV Byzova A Novel Role for Platelet Secretion in Angiogenesis: Mediating Bone Marrow-derived Cell Mobilization and Homing
Blood (2011)



Valerie Altounian/Science Signaling

We have demonstrated that reducing Akt activity might alleviate heart complications and mortality associated with atherosclerosis and heart disease. This image shows an artist's depiction of an atherosclerotic plaque and was inspired by one of our high-profile manuscripts. Kerr BA … TV Byzova Interference with akt signaling protects against myocardial infarction and death by limiting the consequences of oxidative stress
Science Signaling (2013)



Valerie Altounian/Science Signaling

New blood vessel formation, or angiogenesis, is regulated by the expression of integrins, such as αvβ3 and αvβ5, on endothelial cells, platelets, fibroblasts and smooth muscle cells (A). In addition, integrins αvβ3 and αvβ5 control the movement of tumor cells into the blood stream and their arrest at future metastatic sites (B). The αvβ3 is located on bone marrow-derived cells which are recruited to tumors to support tumor growth. Kerr, BA and TV Byzova Integrin Alpha V (ITGAV) Encyclopedia of Signaling Molecules Ed. Sangdun Choi Springer (2013)