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The most cited biological Institute in Russia *

Department of Cell Signalling

The Department was organized in 1977 (initially as the Department of Enzymology) by professor P.P. Philippov, a follower of Professors S.E. Severin and G.A. Kochetov, who is an unchallenged head of the Department until now.

Research areas

  • Molecular mechanisms of phototransduction and visual signalling proteins
    (Dr. E.Yu. Zernii, Dr. I.I. Senin, Dr. N.K. Tikhomirova).
  • Molecular and cellular mechanisms of degeneration and regeneration of the retina
    (O.S. Gancharova, Prof. P.P. Philippov).
  • Cancer-retina antigens
    (Dr. A.V. Bazhin, Dr. M.S. Savchenko, M.O. Golovastova, Dr. E.E. Skorikova, Prof. P.P. Philippov).

Research results

  • Prediction of the existence of the factor capable of activating transducin GTPase [Arshavsky et al. FEBS Lett. 1989;250:353-6].
  • Discovery of the novel Са2+-binding protein p26 or recoverin [Dizhur A.M., Nekrasova E.R., Filippov P.P. New 26 kDa protein specific for photoreceptor cells, capable of binding with immobilized delipidized rhodopsin. Biokhimiya. 1991;56:225-9; Dizhoor et al. Science. 1991;251:915-8; Ray et al. Proc. Natl. Acad. Sci. USA. 1992;89:5705-9; Dizhoor et al. J. Biol. Chem. 1992;267:16033-6; Dizhoor et al. Science. 1993;259:829-32].
  • Identification of rhodopsin kinase as an intracellular target for recoverin [Gorodovikova EN, Philippov PP. FEBS Lett. 1993;335:277-79; Gorodovikova et al. FEBS Lett. 1994;349:187-90; Gorodovikova EN, Senin II, Philippov PP. FEBS Lett. 1994;353:171-2].
  • Demonstration of the higher efficiency of recoverin as an inhibitor of high gain rhodopsin phosphorylation in comparison with light-dependent phosphorylation [Senin et al. Biochem. J. 1997;320:551-5; Senin II, Zargarov AA, Akhtar M, Philippov PP. FEBS Lett. 1997;408:251-4].
  • Elucidation of the functional role of the specific Са2+-binding centers of recoverin [Alekseev et al. FEBS Lett. 1998;440:116-8; Permyakov et al. Protein Eng. 2000;13:783-90; Fisher T, Senin II, Philippov PP, Koch K-W. Spectroscopy 2002;16:271-79; Senin et al. J. Biol. Chem. 2002;52:50365-72; Weiergräber et al. J. Biol. Chem. 2003;278:22972-9; Senin et al. J. Mol. Biol. 2003;330:409-18].
  • Demonstration of the presence of annexins in mammalian photoreceptors [Zernii et al. Annexins. 2004;1:44-50].
  • Detection of autoantibodies against recoverin (anti-Rc) in sera of patients with lung cancer in the absence of paraneoplastic degeneration of the retina; estimation of the anti-Rc frequencies in sera and expression of recoverin in lung tumors [Bazhin et al. Lung Cancer. 2001;34:99-104; Savchenko et al. Lung Cancer. 2003;41:363-67; Bazhin et al. Lung Cancer. 2004;44:193-8].
  • Elucidation of the modulatory role of the recoverin C-terminal fragment and the mechanism of the Са2+-dependent control of rhodopsin kinase by recoverin [Weiergräber OH et al. Tuning of a neuronal calcium sensor. J. Biol. Chem. 2006;281:37594-602; Senin II et al. Membrane binding of the neuronal calcium sensor recoverin - modulatory role of the charged carboxy-terminus. BMC Biochem. 2007;8:24; Komolov KE et al. Mechanism of rhodopsin kinase regulation by recoverin. J. Neurochem. 2009;110:72-9; Zernii EYu et al. Biochem. J. 2011;435:441-50].
  • Detection of recoverin and other key photoreceptor proteins in malignant tumors different from lung tumors; formulation of the conception of cancer-retina antigens [Bazhin AV et al. Recoverin as a cancer-retina antigen. Cancer Immunol. Immunother. 2007;56:110-6; Bazhin AV et al. Photoreceptor proteins as cancer-retina antigens. Int. J. Cancer. 2007;120:1268-76; Bazhin AV et al. Visible light modulates the expression of cancer-retina antigens. Mol. Cancer Res. 2008;6:110-8; Bazhin AV et al. Cancer-retina antigens as potential paraneoplastic antigens in melanoma-associated retinopathy. Int. J. Cancer. 2009;124:140-9].
  • Demonstration of the functional role of the aberrant expression of transducin and cGMP-phosphodiesterase in melanoma cells [Bazhin AV et al. Cell. Mol. Life Sci. 2010;67:817-28].
  • Estimation of the frequencies of autoantibodies against recoverin and other cancer-retina antigens in sera of patients with various malignant tumors [Savchenko MS et al. Autoantibodies against a Ca2+-binding protein recoverin in blood sera of patients with various oncological diseases. Oncol. Lett. 2012;3:377-82].
  • Demonstration of the role of the aberrant demethylation of the recoverin gene in the aberrant expression of this protein in tumor cells [Bazhin AV et al. Aberrant demethylation of the recoverin gene is involved in the aberrant expression of recoverin in cancer cells. Exp. Dermatol. 2010;19:1023-1025].

Grants and projects

Participation in scientific programmes

"Investigation of the visual signalling proteins" jointly with Research Center Jülich and Oldenburg University (Germany); "Investigation of the molecular recognition of visual rhodopsin and rhodopsin kinase" jointly with Polytechnical University of Catalonia and Autonomous University of Barcelona (Spain); "Investigation of the aberrant expression of recoverin in malignant tumors of lung" jointly with Institute of Pulmonology Research Institute, N.N. Blokhin Russian Oncological Scientific Centre, I.M. Setchenov Moscow Medical Academy (Russia), and Philipps-University Marburg (Germany); "Investigation of the effect of antibodies against recoverin upon tumor cells" jointly with Cancer Research Center, University of Heidelberg, and Philipps-University Marburg (Germany); "Investigation of the molecular mechanisms of the aberrant expression of recoverin in malignant tumors" jointly with Brussels Brunch of the Ludwig Institute for Cancer Research (Belgium) and Cancer Research Center, University of Heidelberg (Germany); "Investigation of the aberrant expression of recoverin and other cancer-retina antigens in malignant tumors" jointly with Cancer Research Center and University Hospital Heidelberg, University Heidelberg (Germany).

Grants and stipends

A number of grants from: Russian Foundation for Basic Research and President of Russia; International Human Frontier Science Program; Royal Society and Wellcome Trust (Great Britain); German Research Society for Academic Exchanges, DAAD and German Research Society, DFG (Germany); Ludwig Institute for Cancer Research (USA); Research Center Jülich (Germany); National Center for Scientific Research, CRNS (France); INTAS, and others.

Prizes

Yu.A. Ovchinnikov Award of the Russian Academy of Sciences and Russian Biochemical Society; Stipends of President of Russia and of M.V. Lomonosov Moscow State University.

Educational activity

Training of a number of under- and postgraduate students from Biological and Chemical Faculties, and from Faculty of Bioengineering and Bioinformatics; lecture courses and biochemical workshop for Biological faculty and Faculty of Bioengineering and Bioinformatics.

Employees

Assistant employees

Selected papers Recent papers
  1. Savchenko M.S., Goncharskaia M.A., Skorikova E.E., Eichmuller S.B., Kushlinsky N.E., Bazhin A.V., Philippov P.P. (2012) Autoantibodies against the Ca(2+)-binding protein recoverin in blood sera of patients with various oncological diseases. Oncol. Lett., 3 (2): 377-382. >>

  2. Zernii E.Y., Komolov K.E., Permyakov S.E., Kolpakova T., Dell'orco D., Poetzsch A., Knyazeva E.L., Grigoriev I.I., Permyakov E.A., Senin I.I., Philippov P.P., Koch K.W. (2011) Involvement of the recoverin C-terminal segment in recognition of the target enzyme rhodopsin kinase. Biochemical Journal, 435: 441-450.

  3. Bazhin A.V., de Smet C., Golovastova M.O., Schmidt J., Philippov P.P. (2010) Aberrant demethylation of the recoverin gene is involved in the aberrant expression of recoverin in cancer cells. Experimental Dermatology, 19 (11): 1023-1025.

  4. Bazhin A.V., Tambor V., Dikov B., Philippov P.P., Schadendorf D., Eichmuller S.B. (2010) cGMP-phosphodiesterase 6, transducin and Wnt5a/Frizzled-2-signaling control cGMP and Ca(2+) homeostasis in melanoma cells. Cellular and Molecular Life Sciences, 67 (5): 817-828.

  5. Komolov K.E., Senin I.I., Kovaleva N.A., Christoph M.P., Churumova V.A., Grigoriev I.I., Akhtar M., Philippov P.P., Koch K.W. (2009) Mechanism of rhodopsin kinase regulation by recoverin. Journal of Neurochemistry, 110 (1): 72-79.

  6. Bazhin A.V., Dalke C., Willner N., Abschutz O., Wildberger H.G.H., Philippov P.P., Dummer R., Graw J., de Angel M.H., Schadendorf D., Umansky V., Eichmuller S.B. (2009) Cancer-retina antigens as potential paraneoplastic antigens in melanoma-associated retinopathy. International Journal of Cancer, 124 (1): 140-149.

  7. Grigoryan E.N., Novikova Y.P., Kilina O.V., Philippov P.P. (2007) New method of in vitro culturing of pigment retinal epithelium in the structure of the posterior eye sector of adult rat. Bulletin of Experimental Biology and Medicine, 144 (4): 618-625.

  8. Ramon E., Cordomi A., Bosch L., Zernii E.Y., Senin I.I., Manyosa J., Philippov P.P., Perez J.J., Garriga P. (2007) Critical role of electrostatic interactions of amino acids at the cytoplasmic region of helices 3 and 6 in rhodopsin conformational properties and activation. Journal of Biological Chemistry, 282 (19): 14272-14282.

  9. Bazhin A.V., Schadendorf D., Willner N., de Smet C., Heinzelmann A., Tikhomirova N.K., Umansky V., Philippov P.P., Eichmuller S.B. (2007) Photoreceptor proteins as cancer-retina antigens. International Journal of Cancer, 120 (6): 1268-1276.

  10. Bazhin A.V., Schadendorf D., Philippov P.P., Eichmuller S.B. (2007) Recoverin as a cancer-retina antigen. Cancer Immunology Immunotherapy, 56 (1): 110-116.

  11. Weiergraber O.H., Senin I.I., Zernii E.Y., Churumova V.A., Kovaleva N.A., Nazipova A.A., Permyakov S.E., Permyakov E.A., Philippov P.P., Granzin J., Koch K.W. (2006) Tuning of a neuronal calcium sensor. Journal of Biological Chemistry, 281 (49): 37594-37602.

  12. Senin I.I., Bosch L., Ramon E., Zernii E.Y., Manyosa J., Philippov P.P., Garriga P. (2006) Ca(2+) recoverin dependent regulation of phosphorylation of the rhodopsin mutant R135L associated with retinitis pigmentosa (vol 349, pg 345, 2006). Biochemical and Biophysical Research Communications, 350 (2): 500.

  13. Senin I.I., Bosch L., Ramon E., Zernii E.Y., Manyosa J., Philippov P.P., Garriga P. (2006) Ca(2+)/recoverin dependent regulation of phosphorylation of the rhodopsin mutant R135L associated with retinitis pigmentosa. Biochemical and Biophysical Research Communications, 349 (1): 345-352.

  14. Senin I.I., Hoppner-heitmann D., Polkovnikova O.O., Churumova V.A., Tikhomirova N.K., Philippov P.P., Koch K.W. (2004) Recoverin and rhodopsin kinase activity in detergent-resistant membrane rafts from rod outer segments. Journal of Biological Chemistry, 279 (47): 48647-48653.

  15. Bazhin A.V., Savchenko M.S., Belousov E.V., Jaques G., Philippov P.P. (2004) Stimulation of the aberrant expression of a paraneoplastic antigen, recoverin, in small cell lung cancer cell lines. Lung Cancer, 45 (3): 299-305.

  16. Bazhin A.V., Savchenko M.S., Shifrina O.N., Demoura S.A., Chikina S.Y., Jaques G., Kogan E.A., Chuchalin A.G., Philippov P.P. (2004) Recoverin as a paraneoplastic antigen in lung cancer: the occurrence of anti-recoverin autoantibodies in sera and recoverin in tumors. Lung Cancer, 44 (2): 193-198.

  17. Savchenko M.S., Bazhin A.V., Shifrina O.N., Demoura S.A., Kogan E.A., Chuchalin A.G., Philippov P.P. (2003) Antirecoverin autoantibodies in the patient with non-small cell lung cancer but without cancer-associated retinopathy. Lung Cancer, 41 (3): 363-367.

  18. Senin I.I., Vaganova S.A., Weiergraber O.H., Ergorov N.S., Philippov P.P., Koch K.W. (2003) Functional restoration of the Ca(2+)-myristoyl switch in a recoverin mutant. Journal of Molecular Biology, 330 (2): 409-418.

  19. Weiergraber O.H., Senin I.I., Philippov P.P., Granzin J., Koch K.W. (2003) Impact of N-terminal myristoylation on the Ca(2+)-dependent conformational transition in recoverin. Journal of Biological Chemistry, 278 (25): 22972-22979.

  20. Bazhin A.V., Shifrina O.N., Savchenko M.S., Tikhomirova N.K., Goncharskaia M.A., Gorbunova V.A., Senin I.I., Chuchalin A.G., Philippov P.P. (2001) Low titre autoantibodies against recoverin in sera of patients with small cell lung cancer but without a loss of vision. Lung Cancer, 34 (1): 99-104.

  21. Philippov P.P. (1999) Phototransduction and calcium. Biologicheskie Membrany, 16 (2): 159-168.

  22. Alekseev A.M., Shulga-morskoy S.V., Zinchenko D.V., Shulga-morskaya S.A., Suchkov D.V., Vaganova S.A., Senin I.I., Zargarov A.A., Lipkin V.M., Akhtar M., Philippov P.P. (1998) Obtaining and characterization of EF-hand mutants of recoverin. FEBS Letters, 440 (1): 116-118.

  23. Senin I.I., Zargarov A.A., Akhtar M., Philippov P.P. (1997) Rhodopsin phosphorylation in bovine rod outer segments is more sensitive to the inhibitory action of recoverin at the low rhodopsin bleaching than it is at the high bleaching. FEBS Letters, 408 (3): 251-254.

  24. Senin I.I., Dean K.R., Zargarov A.A., Akhtar M., Philippov P.P. (1997) Recoverin inhibits the phosphorylation of dark-adapted rhodopsin more than it does that of bleached rhodopsin: A possible mechanism through which rhodopsin kinase is prevented from participation in a side reaction. Biochemical Journal, 321: 551-555.

  25. Senin I.I., Zargarov A.A., Alekseev A.M., Gorodovikova E.N., Lipkin V.M., Philippov P.P. (1995) N-Myristoylation of Recoverin Enhances Its Efficiency As An Inhibitor of Rhodopsin Kinase. FEBS Letters, 376 (1): 87-90.

  26. Gorodovikova E.N., Gimelbrant A.A., Senin I.I., Philippov P.P. (1994) Recoverin Mediates the Calcium Effect Upon Rhodopsin Phosphorylation and Cgmp Hydrolysis in Bovine Retina Rod Cells. FEBS Letters, 349 (2): 187-190.

  27. Gorodovikova E.N., Philippov P.P. (1993) The Presence of A Calcium-Sensitive P26-Containing Complex in Bovine Retina Rod Cells. FEBS Letters, 335 (2): 277-279.

  28. Dizhur A.M., Nekrasova E.N., Filippov P.P. (1991) A Novel Photoreceptor Cell-Specific Protein with Molecular-Weight 26-Kd Capable of Binding to Immobilized Delipidated Rhodopsin. Biochemistry-Moscow, 56 (2): 123-126.

  29. Dizhoor A.M., Nekrasova E.R., Philippov P.P. (1989) The Binding of G-Proteins to Immobilized Delipidated Rhodopsin. Biochemical and Biophysical Research Communications, 162 (1): 544-549.