Additional Contact Information:
Department of Biomedical Sciences
Center of Excellence for Inflammation,
Infectious Disease and Immunity
PO Box 70577
Carl A Jones Hall (VA Bldg. 1),
Office 1-31/ lab 130
James H. Quillen College of Medicine
East Tennessee State University
Johnson City, TN 37614
Phone: (423) 439-8511
My laboratory has been focused on studying the structural and functional properties of leukocyte integrins. Integrins are cell surface signaling receptors, which are involved in cell adhesion and migration during different physiological and pathological conditions. Particularly, we are interested in the mechanism of integrin αDβ2- and integrin αMβ2-mediated recruitment and accumulation of macrophages during chronic inflammatory diseases such as atherosclerosis, diabetes and obesity as well as acute inflammation such as 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
- To evaluate a mechanism of integrin-mediated cell adhesion and migration.
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.
Current Research Support
American Heart Association, (AIREA)
20AIREA35150018 (Yakubenko) 01/01/2020-01/01/2022
“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.
Intramural Quillen College of Medicine Research Enhancement Award
Contribution of α7 nicotinic acetylcholine receptor (α7nAChR) to macrophage migration during inflammation.
Role: Principal Investigator.
The major goal of this award to evaluate the role of α7nAChR in macrophage functions during inflammatory response.
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.
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.
1. 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.
2. Yakubenko VP, Byzova TV. Biological and pathophysiological roles of end-products of DHA oxidation. Biochim. Biophys. Acta. 2017 Apr;1862(4):407-415.
3. 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.
4. 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 V, 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.
5. Szpak D, Izem L, Verbovetskiy D, Soloviev DA, Yakubenko VP, Pluskota E. αMβ2 Is Antiatherogenic in Female but Not Male Mice. Journal of Immunology, 2018 Apr 1;200(7):2426-2438.
6. Lishko VK, Yakubenko VP, Ugarova TP, Podolnikova NP. Leukocyte integrin Mac-1 (CD11b/CD18) acts as a functional receptor for platelet factor 4. J Biol Chem. 2018 May 4;293(18):6869-6882
7. 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.
*- corresponding author
8. Dhabal S, Das P, Biswas P, Kumari P, Yakubenko VP, Kundu S, Cathcart MK, Kundu M, Biswas K, Bhattacharjee A. Regulation of monoamine oxidase A (MAO-A) expression, activity and function in IL-13-stimulated monocytes and A549 lung carcinoma cells. J Biol Chem. 2018 Jul 18.
9. 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
10. 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;
11. 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)
12. 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. 2020. Accepted December 9, 2020. Selected by the editorial board for the Frontline Science Section as "Leading Edge Research".
Complete list of publications in PubMed: http://www.ncbi.nlm.nih.gov/sites/myncbi/valentin.yakubenko.1/bibliography/48660078/public/?sort=date&direction=ascending