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
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.
ABSTRACTS (selected from more than 150):
|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.|
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 2008 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.
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
We have demonstrated that reducing
Akt activity might alleviate heart
complications and mortality
associated with atherosclerosis and
This image shows an artist's depiction
of an atherosclerotic plaque and was
inspired by one of our high-profile
Kerr BA … TV Byzova
Interference with akt signaling
protects against myocardial infarction
and death by limiting the
consequences of oxidative stress
Science Signaling (2013)
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)