Sergey Ryzhov

Education

  • PhD, Siberian State Medical University, Russia, 1999

Research Interests

My research focuses on the role of interactions between immune and cardiac cells during heart recovery after myocardial injury. Research interests center on two general areas: the protective role of myeloid cells in ischemic tissues and its potential for cardiac revascularization and regeneration and role of neuregulin signaling in control of pro-inflammatory activation of immune cells.

Myocardial infarction (MI) is characterized by a marked cellular inflammatory response. CD45 positive immune cells rapidly infiltrate injured myocardium, their numbers peaking at day 5 after MI when they become almost as abundant as all CD45 negative non-myocyte cells (endothelial cell, fibroblasts, myofibroblasts, smooth muscle cells etc) combined. Among immune cells, myeloid cells represent the majority of infiltrating cells during the periods of acute inflammation and early granulation tissue formation after ischemic myocardial injury. Mature myeloid mononuclear cells (macrophages and monocyte-derived dendritic cells) stimulate angiogenesis, thus contributing to regeneration after cardiac injury.

Neuregulins (NRGs) belong to the epidermal growth factor (EGF) superfamily of transmembrane growth factors NRG-1 has been intensively studied due to its essential role in cardiac development and in regulation of the adult cardiovascular system adaptation to physiological and pathological stress. Monocytes express ERBB receptors and neuregulin-1 signaling pathway in myeloid cells contributes to resolution of inflammation by promoting the functional shift from cytokine-secreting “pro-inflammatory” toward phagocytic “pro-resolution” phenotype.

Selected Publications

  • Yuryeva K., Saltykova I., Ogorodova L., Kirillova N., Kulikov E., Korotkaya E., Iakovleva Y., Feoktistov I., Sazonov A., Ryzhov S. Expression of adenosine receptors in monocytes from patients with bronchial asthma. Biochem Biophys Res Commun, 2015 PMCID: PMC In Process
  • Paik D.T., Rai M., Ryzhov S., Sanders L.N., Aisagbonhi O., Funke M.J., Feoktistov I., Hatzopoulos A.K. Wnt10b Gain-of-Function Improves Cardiac Repair by Arteriole Formation and Attenuation of Fibrosis. Circ Res. 2015 PMCID: PMC In Process
  • Ryzhov S, Biktasova A, Goldstein AE, Zhang Q, Biaggioni I, Dikov MM, Feoktistov I. Role of JunB in adenosine A2B receptor-mediated VEGF production. Mol Pharm 2014; 85(1):62-73.
  • Galindo C.L., Ryzhov S., Sawyer D.B. Neuregulin as a heart failure therapy and mediator of reverse remodeling. Curr Heart Fail Rep. 2014; 11(1):40-49. PMCID: PMC3975684.
  • Ryzhov S., Sung BH, Zhang Q, Weaver A, Gumina RJ, Biaggioni I, Feoktistov I. Role of adenosine A2B receptor signaling in contribution of cardiac mesenchymal stem-like cells to myocardial scar formation. Purinergic Signal. 2014; 10(3):477-86. PMCID: PMC4152448.
  • Galindo CL, Kasasbeh E, Murphy A, Ryzhov S, Lenihan S, Ahmad FA, Williams P, Nunnally A, Adcock J, Song Y, Harrell FE, Tran TL, Parry TJ, Iaci J, Ganguly A, Feoktistov I, Stephenson MK, Caggiano AO, Sawyer DB, Cleator JH. Anti-remodeling and Anti-fibrotic Effects of the Neuregulin-1β Glial Growth Factor 2 in a Large Animal Model of Heart Failure. J Am Heart Assoc. 2014;3(5). PMCID: PMC4323814
  • Ryzhov S, Pickup P.W., Chytil A., Zhang Q., Owens P., Feoktistov I., Moses H.L., Novitskiy S.V. Role of TGFβ signaling in generation of CD39+CD73+ myeloid cells in tumors. J Immunol. 2014; 193(6):3155-164. PMCID:PMC4157098
  • Atochina-Vasserman E.N., Biktasova A., Abramova E., Cheng D.S., Polosukhin V.V., Tanjore H., Takahashi S., Sonoda H., Foye L., Venkov C., Ryzhov S.V., Novitskiy S., Shlonimskaya N., Ikeda M., Blackwell T.S., Lawson W.E., Gow A.J., Harris R.C., Dikov M.M., Tchekneva E.E. Aquaporin 11 insufficiency modulates kidney susceptibility to oxidative stress. Am J Physiol Renal Physiol. 2013; 304(10):F1295-1307. PMCID: PMC3651623.
  • Ryzhov S, Zhang Q, Biaggioni I, Feoktistov I. Adenosine A2B Receptors on Cardiac Stem Cell Antigen (Sca)-1-Positive Stromal Cells Play a Protective Role in Myocardial Infarction. Am J Pathol. 2013; 183(3):665-672. PMCID: PMC3763763.
  • Ryzhov S., Goldstein A.E., Novitskiy S.V., Blackburn M.R., Biaggioni I., Feoktistov I. Role of A2B adenosine receptors in regulation of paracrine functions of stem cell antigen 1-positive cardiac stromal cells. J Pharmacol Exp Ther. 2012; 341(3):764-774. PMCID: PMC3362889.
  • Transition. Dis. Model Mech 2011; 4(4): 469-483 PMCID: PMC3124051.
  • Ryzhov S, Novitskiy SV, Goldstein AE, Biktasova A, Blackburn MR, Biaggioni I, Dikov MM, Feoktistov I. Adenosinergic Regulation of the Expansion and Immunosuppressive Activity of CD11b+Gr1+ Cells. J Iimmunol. 2011; 187(11):6120-6129. PMCID: PMC3221925.
  • Zaynagetdinov R., Ryzhov S., Goldstein A.E., Novitskiy S.V., Goleniewska K., Polosukhin V.V., Yin H., Morschl E., Zhou Y., Mitchell D., Blackburn M.R., Peebles R.S., Biaggioni I, Feoktistov I, Attenuation of Allergen-Induced Chronic Pulmonary Inflammation in A2B Adenosine Receptor Knockout Mice. American Journal of Respiratory Cell and Molecular Biology 2010; 42(5):564-71. PMCID: PMC2874442.
  • Ryzhov S., Zaynagetdinov R., Goldstein A.E., Matafonov A., Biaggioni I., Feoktistov I. Differential role of the carboxy-terminus of the A(2B) adenosine receptor in stimulation of adenylate cyclase, phospholipase Cbeta, and interleukin-8. Purinergic Signalling 2009; 5(3):289-298. PMCID: PMC2717310.
  • Regulation of Proinflammatory Cytokines. J Pharmacol Exp Ther. 2008; 324(2): 694-700.
  • Ryzhov S., Solenkova N.V., Goldstein A.E., Lamparter M., Fleenor T., Young P.P., Greelish J.P., Byrne J.G, Vaughan D.E., Biaggioni I., Hatzopoulos A.K., Feoktistov I. Adenosine Receptor–Mediated Adhesion of Endothelial Progenitors to Cardiac Microvascular Endothelial Cells. Circ Res. 2008; 102(3): 356-363. PMCID: PMC2803108.
  • signaling in mast cells. J Iimmunol. 2008; 180(11):7212-7220.
  • Novitsky S.V., Ryzhov S., Huang Y., Tikhomirov O.Y., Biaggioni I., Carbone D.P., Feoktistov I., Dikov M.M. Adenosine receptors in regulation of dendritic cell differentiation and function. Blood. 2008; 112(5):1822-1831. PMCID: PMC2518889.
  • Ryzhov S., Novitsky S.V, Zaynagetdinov R., Goldstein A.E., Carbone D.P., Biaggioni I., Dikov M.M., Feoktistov I. Host A2B Adenosine Receptors Modulate Carcinoma Growth. Neoplasia. 2008; 10(9):987-995. PMCID: PMC2517644.
  • Ryzhov S., McCaleb J.L., Goldstein A.E., Biaggioni I., Feoktistov I. Role of Adenosine Receptors in the Regulation of Angiogenic Factors and Neovascularization in Hypoxia. J Pharmacol Exp Ther. 2007; 320(2): 565-572.
  • Ryzhov S, Goldstein A.E., Biaggioni I., Feoktistov I. Cross-Talk between Gs- and Gq-Coupled Pathways in Regulation of Interleukin-4 by A2B Adenosine Receptors in Human Mast Cells. Mol Pharmacol. 2006; 70(2): 727-735.
  • Babaev V.R., Yancey P.G., Ryzhov S.V., Kon V., Breyer M.D., Magnuson M.A., Fazio S., Linton M.F. Conditional Knockout of Macrophage PPAR Increases Atherosclerosis in C57BL/6 and Low Density Lipoprotein Receptor–Deficient Mice. Arteriosclerosis, Thrombosis, and Vascular Biology. 2005; 25: 1647-1653.
  • Ryzhov S., Goldstein A.E., Matafonov A., Zeng D., Biaggioni I. Feoktistov I. Adenosine-activated mast cells induce IgE synthesis by B lymphocytes: an A2B-mediated process involving Th2 cytokines IL-4 and IL-13 with implications for asthma. J Immunol. 2004; 172(12):7726-7733.
  • Adenosine Receptors in Human Endothelial and Smooth Muscle Cells Towards an A2B Angiogenic Phenotype. Hypertension. 2004; 44(5):649-654.