Tatiana Byzova Laboratory

Research

Overview

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, MD, Urology
• Eric Klein, MD, Urology
• Brian Rini, MD, Solid Tumor Oncology
• Andrew Stephenson, MD, Urology
• Bruce Trapp, PhD, Neurosciences
• Dimitrios Davalos, PhD, Neurosciences
• Matt Kalaycio, MD, Hematology Oncology

Project Highlights

Picture taken by Bethany Kerr / Cleveland Clinic

We have demonstrated that Akt pathway is crucial for vascular function and vascular integrity in adults. Interference with this pathway in endothelial cells leads to a loss of smooth muscle cells, vasculature deterioration, and poor tissue perfusion. This causes organ dysfunction, first of all cardiac abnormalities and retina degeneration. Kerr BA … Byzova TV Stability and function of adult vasculature is sustained by Akt/Jagged1 signalling axis in endothelium Nature Communications (2016)

Picture taken by X. West, multiple images reconstructed by R. Cull / Cleveland Clinic

We have demonstrated a novel mechanism of recognition and clearance of oxidized lipid metabolites, which were previously believed to be end-products of oxidative process. These oxidized lipid metabolites accumulate in atherosclerotic lesions of blood vessels, including aortas (shown on the cover). The study shows that high levels of oxidized products found in pathologies, including atherosclerosis and cancer, might be due to their insufficient clearance by macrophages. Kim YW … Byzova TV Receptor-Mediated Mechanism Controlling Tissue Levels of Bioactive Lipid Oxidation Products
Circulation Research (2015)

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)

Selected Publications

View publications for Tatiana Byzova, PhD
(Disclaimer: This search is powered by PubMed, a service of the U.S. National Library of Medicine. PubMed is a third-party website with no affiliation with Cleveland Clinic.)

Xiong L, McCoy M, Komuro H, West XZ, Yakubenko V, Gao D, Dudiki T, Milo A, Chen J, Podrez EA, Trapp B, Byzova TV.(2022) Inflammation-dependent oxidative stress metabolites as a hallmark of amyotrophic lateral sclerosis. Free Radic Biol Med. 178:125-133. PMID: 34871763; PMCID: PMC8744315

McCoy MG, Nascimento DW, Veleeparambil M, Murtazina R, Gao D, Tkachenko S, Podrez E, Byzova TV. (2021) Endothelial TLR2 promotes proangiogenic immune cell recruitment and tumor angiogenesis. Sci Signal. 14(666):eabc5371. PMID: 33986920; PMCID: PMC8112454

Kerr BA, Harris KS, Shi L, Willey JS, Soto-Pantoja DR, Byzova TV. (2021) Platelet TSP-1 controls prostate cancer-induced osteoclast differentiation and bone marrow-derived cell mobilization through TGFβ-1. Am J Clin Exp Urol. 9(1):18-31. PMID: 33816691; PMCID: PMC8012834

Dudiki T, Mahajan G, Liu H, Zhevlakova I, Bertagnolli C, Nascimento DW, Kothapalli CR, Byzova TV. (2021) Kindlin3 regulates biophysical properties and mechanics of membrane to cortex attachment. Cell Mol Life Sci. 2021 Mar 30. PMID: 33783564

Biswas S, Gao D, Altemus JB, Rekhi UR, Chang E, Febbraio M, Byzova TV, Podrez EA. (2021) Circulating CD36 is increased in hyperlipidemic mice: Cellular sources and triggers of release. Free Radic Biol Med. 168:180-188. PMID: 33775772

Kerr BA, Shi L, Jinnah AH, Harris KS, Willey JS, Lennon DP, Caplan AI, Byzova TV. (2021) Kindlin-3 mutation in mesenchymal stem cells results in enhanced chondrogenesis. Exp Cell Res. 399(2):112456. PMID: 33417921; PMCID: PMC7874523

Podrez EA, Byzova TV. (2020) Remodeling vasculature to avoid blindness. Science 369(6506):919-920. PMID: 32820112

Liu H, Zhu L, Dudiki T, Gabanic B, Good L, Podrez EA, Cherepanova OA, Qin J, Byzova TV. (2020) Macrophage Migration and Phagocytosis Are Controlled by Kindlin-3's Link to the Cytoskeleton. J Immunol. 204(7):1954-1967. PMID: 32094207

Dudiki T, Meller J, Mahajan G, Liu H, Zhevlakova I, Stefl S, Witherow C, Podrez E, Kothapalli CR, Byzova TV. (2020) Microglia control vascular architecture via a TGFβ1 dependent paracrine mechanism linked to tissue mechanics. Nat Commun. 11(1):986. PMID: 32080187; PMCID: PMC7033106

Gao D, Ashraf MZ, Zhang L, Kar NS, Byzova TV, Podrez EA. (2020) Cross-linking modifications of HDL apoproteins by oxidized phospholipids: Structural characterization, in vivo detection, and functional implications. J Biol Chem. 295(7):1973-1984. PMID: 31907281; PMCID: PMC7029106

Zhu L, Liu H, Lu F, Yang J, Byzova TV, Qin J. (2019) Structural Basis of Paxillin Recruitment by Kindlin-2 in Regulating Cell Adhesion. Structure. 27(11):1686-1697.e5. PMID: 31590942; PMCID: PMC6894617

Cui K, Podolnikova NP, Bailey W, Szmuc E, Podrez EA, Byzova TV, Yakubenko VP. (2019) Inhibition of integrin αDβ2-mediated macrophage adhesion to end product of docosahexaenoic acid (DHA) oxidation prevents macrophage accumulation during inflammation. J Biol Chem. 294(39):14370-14382. PMID: 31395659; PMCID: PMC6768641

Yakubenko VP, Cui K, Ardell CL, Brown KE, West XZ, Gao D, Stefl S, Salomon RG, Podrez EA, Byzova TV. (2018) Oxidative modifications of extracellular matrix promote the second wave of inflammation via β2 integrins. Blood. 132(1):78-88. PMID: 29724896; PMCID: PMC6034644

Zhu L, Yang J, Bromberger T, Holly A, Lu F, Liu H, Sun K, Klapproth S, Hirbawi J, Byzova TV, Plow EF, Moser M, Qin J. (2017) Structure of Rap1b bound to talin reveals a pathway for triggering integrin activation. Nat Commun. 8(1):1744. PMID: 29170462; PMCID: PMC5701058

Feng W, Valiyaveettil M, Dudiki T, Mahabeleshwar GH, Andre P, Podrez EA, Byzova TV. (2017) β3 phosphorylation of platelet αIIbβ3 is crucial for stability of arterial thrombus and microparticle formation in vivo. Thromb J. 15:22. PMID: 28860945; PMCID: PMC5576334

Biswas S, Zimman A, Gao D, Byzova TV, Podrez EA. (2017) TLR2 Plays a Key Role in Platelet Hyperreactivity and Accelerated Thrombosis Associated With Hyperlipidemia. Circ Res. 121(8):951-962. PMID: 28775078; PMCID: PMC5623081

Meller J, Chen Z, Dudiki T, Cull RM, Murtazina R, Bal SK, Pluskota E, Stefl S, Plow EF, Trapp BD, Byzova TV. (2017) Integrin-Kindlin3 requirements for microglial motility in vivo are distinct from those for macrophages. JCI Insight. 2(11). pii: 93002. PMID: 28570266; PMCID: PMC5453700

Yakubenko VP, Byzova TV. (2017) Biological and pathophysiological roles of end-products of DHA oxidation. Biochim Biophys Acta Mol Cell Biol Lipids. 1862(4):407-415. PMID: 27713004; PMCID: PMC5360178

Ding L, Zhang L, Biswas S, Schugar RC, Brown JM, Byzova T, Podrez E. (2017) Akt3 inhibits adipogenesis and protects from diet-induced obesity via WNK1/SGK1 signaling. JCI Insight. 2(22). pii: 95687. PMID: 29202451; PMCID: PMC5752373

Ding L, Zhang L, Kim M, Byzova T, Podrez E. (2017) Akt3 kinase suppresses pinocytosis of low-density lipoprotein by macrophages via a novel WNK/SGK1/Cdc42 protein pathway. J Biol Chem. 292(22):9283-9293. PMID: 28389565; PMCID: PMC5454109

Byzova TV. (2016) "Fishing" out the real VEGFs. Blood. 128(19):2283-2284. PMID: 28829753; PMCID: PMC5106111

Gao F, Artham S, Sabbineni H, Al-Azayzih A, Peng XD, Hay N, Adams RH, Byzova TV, Somanath PR. (2016) Akt1 promotes stimuli-induced endothelial-barrier protection through FoxO-mediated tight-junction protein turnover. Cell Mol Life Sci. 73(20):3917-33. PMID: 27113546; PMCID: PMC5023469

Biswas S, Xin L, Panigrahi S, Zimman A, Wang H, Yakubenko VP, Byzova TV, Salomon RG, Podrez EA. (2016) Novel phosphatidylethanolamine derivatives accumulate in circulation in hyperlipidemic ApoE-/- mice and activate platelets via TLR2. Blood. 127(21):2618-29. PMID: 27015965; PMCID: PMC4882806

Kerr BA, West XZ, Kim YW, Zhao Y, Tischenko M, Cull RM, Phares TW, Peng XD, Bernier-Latmani J, Petrova TV, Adams RH, Hay N, Naga Prasad SV, Byzova TV. (2016) Stability and function of adult vasculature is sustained by Akt/Jagged1 signalling axis in endothelium. Nat Commun. 7:10960. PMID: 26971877; PMCID: PMC4793084

Podrez EA, Byzova TV. (2016) Prothrombotic lipoprotein patterns in stroke. Blood. 127(10):1221-2. PMID: 26965920; PMCID: PMC4786832

Kim YW, Yakubenko VP, West XZ, Gugiu GB, Renganathan K, Biswas S, Gao D, Crabb JW, Salomon RG, Podrez EA, Byzova TV. (2015) Receptor-Mediated Mechanism Controlling Tissue Levels of Bioactive Lipid Oxidation Products. Circ Res. 117(4):321-32. PMID: 25966710; PMCID: PMC4522201

Bialkowska K, Byzova TV, Plow EF. (2015) Site-specific phosphorylation of kindlin-3 protein regulates its capacity to control cellular responses mediated by integrin αIIbβ3. J Biol Chem. 290(10):6226-42. PMID: 25609252; PMCID: PMC4358261

Kerr BA, Miocinovic R, Smith AK, West XZ, Watts KE, Alzayed AW, Klink JC, Mir MC, Sturey T, Hansel DE, Heston WD, Stephenson AJ, Klein EA, Byzova TV. (2015)CD117⁺ cells in the circulation are predictive of advanced prostate cancer. Oncotarget. 6(3):1889-97. PMID: 25595903; PMCID: PMC4359340

Meller J, Rogozin IB, Poliakov E, Meller N, Bedanov-Pack M, Plow EF, Qin J, Podrez EA, Byzova TV. (2015) Emergence and subsequent functional specialization of kindlins during evolution of cell adhesiveness. Mol Biol Cell. 26(4):786-96. PMID: 25540429; PMCID: PMC4325847