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Additional Contact Information: Department of Biomedical Sciences |
EDUCATION/PROFESSIONAL EXPERIENCE
Dr. Yakubenko received Ph.D. in biochemistry in the National Academy of Science of Ukraine. He obtained a post-doctoral training in cell and molecular biology in the Lerner Research Institute at the Cleveland Clinic. He was a research faculty in the Cleveland Clinic before joining ETSU in 2015.RESEARCH/TEACHING INTERESTS
My laboratory has been focused on studying the mechanism of leukocyte migration during acute and chronic inflammation. One of our major interests is the family of cell adhesive receptors – integrins. Integrins are cell surface heterodimers, which are involved in cell adhesion and migration during different physiological and pathological conditions. Particularly, we are interested in the function of integrin αDβ2 and integrin αMβ2 on macrophages and neutrophils during the development of atherosclerosis, diabetes and sepsis. There are several major directions in our research:
- To understand the role of integrins in pathophysiological processes including cardiovascular diseases, metabolic dysfunction and sepsis.
- To characterize the integrin-ligand interactions and to identify integrin ligand binding
motifs.
- To evaluate a mechanism of integrin-mediated cell adhesion and migration.
Another project in our laboratory is focused on studying the contribution of α7 nicotinic acetylcholine receptor (α7nAChR) to macrophage migration during inflammation. α7nAChR is a ligand-gated ion channel, which in addition to its classical expression on neurons, is expressed on several types of immune cells, including lymphocytes, monocytes and macrophages. It has been demonstrated that the stimulation of the vagal nerve, which constitutes the main parasympathetic tract, promotes signaling via macrophage-expressed α7nAChR that activates a cholinergic anti-inflammatory pathway. The goal of this project is to determine the mechanism of macrophage migration regulated by the autonomic nervous system. We hypothesize that α7nAChR activation affects macrophage migration during inflammation by changing the expression of cell adhesive receptors, that modifies the overall α7nAChR-mediated anti-inflammatory response.
We used different protein chemistry, cell and molecular biology approaches for our studies, such as molecular cloning and mutagenesis, real time PCR, expression and analysis of recombinant proteins, adhesion and migration of transfected cell lines and primary leukocytes, fluorescent microscopy, flow cytometry, imaging flow cytometry and mouse models of inflammation – atherosclerosis, diabetes, sepsis, endotoxemia and peritonitis.
ACTIVE RESEARCH FUNDING
Current Research Support
Ongoing:
National Institute of Health, NHLBI
R15 HL157836-01 Yakubenko (PI) 02/01/2022-01/31/2025
“The role of a neuro-immune synapse in macrophage migration”.
Role: Principal Investigator.
The major goal of this award is to evaluate the role of α7nAChR in macrophage migration during the inflammatory response.
American Heart Association
20AIREA35150018 (Yakubenko) (PI) 01/01/2020-12/31/2022, NCE
“Targeting the product of DHA oxidation as potential substrate for macrophage retention during atherosclerosis”.
Role: Principal Investigator.
The major goal of this study is to determine the molecular mechanism of interaction between macrophage integrins and ECM proteins modified by the end-product of DHA oxidation during the development of atherosclerosis.
Department of Veterans Affairs (VA)
BX004045 Singh, Krishna (PI) 04/01/2018 - 03/31/2023
Investigation of therapeutic potential of exogenous ubiquitin following myocardial ischemia/reperfusion injury.
Role: Co-I
Completed last 3 years:
National Institute of Health, NIDDK
1R01 DK102020-01 (Yakubenko) 07/01/2014 - 04/30/2020 (no cost extension)
“Role of β2 integrins in macrophage retention and egress during inflammation”.
Role: Principal Investigator
The purpose of this proposal is to test the role of leukocyte migratory receptors, integrins αMβ2 and αDβ2, in the retention and egress of macrophages within the site of chronic inflammation during the development of metabolic syndrome.
American Heart Association, Great Rivers Affiliate, Grant-in-Aid
14GRNT20410074 (Yakubenko) 07/01/2014 – 06/30/2016
“The contribution of integrin αDβ2 to the macrophage migration and lipid deposition during atherogenesis.”
Role: Principal Investigator
This project will focus on the determination of the impact of integrin αDβ2 on the development of atherosclerosis, focusing on both components of early atherogenesis – macrophage accumulation and lipid deposition.
PUBMED
Complete List of PubMed Publications
SELECTED PUBLICATIONS
- Casteel JL, Keever KR, Ardell CL, Williams DL, Gao D, Podrez EA, Byzova TV, Yakubenko VP. Modification of extracellular matrix by the product of DHA oxidation switches macrophage adhesion patterns and promotes retention of macrophages during chronic inflammation. Frontiers in immunology. 2022 May 26;13:867082.
- Xiong L, McCoy M, Komuro H, West XZ, Yakubenko VP, Gao D, Dudiki T, Milo A, Chen J, Podrez EA, Trapp B, Byzova TV. Inflammation-dependent oxidative stress metabolites as a hallmark of amyotrophic lateral sclerosis. Free Radic Biol Med. 2022 Jan;178:125-133.
- Bailey WP, Cui K, Ardell CL, Keever KR, Singh S, Rodriguez-Gil DJ, Ozment TR, Williams DL, Yakubenko VP. The expression of integrin αDβ2 (CD11d/CD18) on neutrophils orchestrates the defense mechanism against endotoxemia and sepsis. J Leuk Biol. 2021 May;109(5):877-890.The paper was selected as Frontline Science and received Editorial commentary: Liwu Li. J Leuk Biol. 2021 109(5):861-863
- Cui K, Podolnikova NP, Bailey W, Szmuc E, Podrez EA, Byzova TV, Yakubenko VP. Inhibition of Integrin αDβ2-mediated Macrophage Adhesion to End-product of DHA Oxidation Prevents Macrophage Accumulation during Inflammation. J Biol Chem. 2019 Sep 27;294(39).
- Podolnikova NP, Hlavackova M, Wu Y, Yakubenko VP, Faust J, Balabiyev A, Wang X, Ugarova TP. Interaction between the integrin Mac-1 and signal regulatory protein α (SIRPα) mediates fusion in heterologous cells. J Biol Chem. 2019 May 10;
- Cui K, Aziz M, Ardell CL, Podolnikova NP, Yakubenko VP. Distinct migratory properties of resident, classically and alternatively-activated macrophages are regulated by αDβ2 and αMβ2 integrin-mediated adhesion. Frontiers in immunology. 2018; 9:2650.
- Yakubenko VP, Cui K, Ardell CL, Brown KE, West XZ, Salomon RG, Podrez EA, Byzova TV. Oxidative
modifications of extracellular matrix promote the second wave of inflammation via
β2 Integrins. Blood. 2018 Jul 5;132(1):78-88.
- Wolf D., Anto-Michel N., Blankenbach H., Wiedemann A., Buscher K., Hohmann JD, Lim B, Bäuml M, Marki A, Mauler M, Duerschmied D, Fan Z., Winkels H, Sidler D, Diehl P, Zajonc D., Hilgendorf I., Stachon P, Schell M, Sommer B., von Muhlen K., Plow E., Yakubenko VP, Libby P., Bode C., Ley K., Peter K., and Zirlik A. A ligand-specific blockade of the integrin Mac-1 selectively targets pathologic inflammation while maintaining protective host-defense. Nature Communications 2018 Feb 6;9(1):525.
- Aziz M, Cui K, Das M, Brown KE, Ardell CL, Febbraio M, Pluskota E, Wu H, Ballantyne CM, Smith JD, Cathcart MK, Yakubenko VP. The upregulation of integrin αDβ2 (CD11d/CD18) on inflammatory macrophages promotes macrophage retention in vascular lesions and development of atherosclerosis. Journal of Immunology. 2017 Jun 15;198(12):4855-4867.
- Yakubenko VP, Byzova TV. Biological and pathophysiological roles of end-products of DHA oxidation. Biochim. Biophys. Acta. 2017 Apr;1862(4):407-415.
- Liu J, Das M, Yang J, Ithychanda SS, Yakubenko VP, Plow EF, and Qin J. Structural mechanism of integrin inactivation by filamin. Nature Structural and Molecular Biology 2015 May;22(5):383-9.