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Никитенко Леонид Леонидович

Научная тема: « РОЛЬ АДРЕНОМЕДУЛЛИНА И ЕГО РЕЦЕПТОРОВ В ФУНКЦИОНИРОВАНИИ ЭНДОТЕЛИАЛЬНОЙ КЛЕТКИ ЧЕЛОВЕКА (В НОРМЕ И ПРИ НЕКОТОРЫХ ПАТОЛОГИЯХ) »

Научная биография   « Никитенко Леонид Леонидович »

Членство в Российской Академии Естествознания

Специальность: 14.00.16

Год: 2007

Отрасль науки: Биологические науки

Основные научные положения, сформулированные автором на основании проведенных исследований:

  1. АМ является новым ангиогенным фактором в тканях человека за счет своей способности активировать пролиферацию и миграцию, а также ингибировать апоптоз эндотелиальных клеток микроциркуляторного русла.
  2. Экспрессия CALCRL гена человека зависит прежде всего от клеточно- и ткане-специфического фона. При этом ключевым фактором в транскрипции CALCRL гена является его трехмерная субхромосомная структура, в то время как активность промотера играет вторичную роль.
  3. Десенситизация CL рецептора в эндотелиальных клетках человека при избыточной экспрессии лиганда отражается на его функции и может играть роль при развитии сердечно-сосудистых заболеваний различной этиологии.
  4. Разработанные реактивы и методы могут применяться для диагностики и коррекции патологий связанных с функцией адреномедуллиновых рецепторов, например патологического ангиогенеза и гиперпроницаемости эндотелия.
  5. Разработана и применена концепция системного анализа механизмов комплексной многоуровнево-селективной регуляции экспрессии и функции адреномедуллиновых рецепторов, а также их роли в полноценном функционировании эндотелиальной клетки в норме и при патологии.

Список опубликованных работ

1. Oehler MK, Nikitenko LL, Hague S, Bicknell R, Rees MCP. Expression of the angiogenic growth factor adrenomedullin in endometrial carcinoma cell lines and endometrial adenocarcionoma. Xth Hamburg Symposium on Tumor Markers, Hamburg, Germany – 1999. – P. 112.

2. Oehler MK, Nikitenko LL, Hague S, Bicknell R, Rees MCP. Prognostic relevance of serum vascular endothelial growth factor in ovarian cancer. // Xth Hamburg Symposium on Tumor Markers, Hamburg, Germany. – 1999. – P. 128.

3. Nikitenko LL, MacKenzie IZ, Rees MCP, Bicknell R. Adrenomedullin is an autocrine regulator of endothelial growth in human endometrium. // Molecular Human Reproduction. – 2000. – Vol. 6 (9). – P. 811-819.

4. Nikitenko LL, Lloyd BH, Rudland PhS, and Barraclough R. Localisation by in situ hybridisation of S100A4 (p9Ka) mRNA in primary human breast tumour specimens. // International Journal of Cancer. – 2000. – Vol. 86. – P. 219-228.

5. Nikitenko LL, MacKenzie IZ, Bicknell R, Rees MCP. Adrenomedullin/CGRP receptors in the human uterus. // XIth International Congress of Histochemistry and Cytochemistry, York, United Kingdom. – 2000. – P. 234.

6. Nikitenko LL, MacKenzie IZ, Rees MCP, Bicknell R. Isolation, culture and growth factor responsiveness of human endometrial endothelium. // Annual ICRF Colloquium, Warwick, United Kingdom– 2000. – P. 54.

7. Nikitenko LL, MacKenzie I, Rees MCP, Bicknell R. Adrenomedullin is an autocrine regulator of endothelial growth in human endometrium. // Introduction to Molecular and Cellular Research, San-Diego, USA. – 2000. – P. 97.

8. Nikitenko LL, Brown NS, Smith DM, MacKenzie I, Bicknell R, Rees MCP. Differential and cell-specific expression of calcitonin-receptor-like receptor and receptor activity modifying proteins in the human uterus. // Molecular Human Reproduction. – 2001. – Vol. 7(7). – P. 655-664.

9. Nikitenko LL, Smith DM, Hague S, Wilson CR, Bicknell R, Rees MCP. Adrenomedullin and the Microvasculature. // Trends in Pharmacological Sciences. – Vol. 23(3). – P. 101-103.

10. Rees MCP, Nikitenko LL, Hague S, Bicknell R. Endometrial angiogenesis. In: Maruo T, Barlow D, Mardon H, Kennedy S. (eds) Cell and Molecular Biology of Endometrium in Health and Disease. Soeshi Publishing. – 2002. – P. 145-155.

11. Wilson CR, Nikitenko LL, Smith DM, Sargent IL, Rees MCP. Expression of adrenomedullin and its receptors in placenta and decidua. // 8th IFPA Meeting, Melbourne, Australia. – 2002. – P. – 121.

12. Nikitenko LL, Patel S, Clissold P, Rees MCP, Bicknell R. Molecular characterization of the adaptive response of endothelial cells to hypoxia. // Angiogenesis: basic mechanisms and therapeutic implications, Ascona, Switzerland. – 2002. – P. - 27.

13. Nikitenko LL, Rees MCP, Bicknell R. Adrenomedullin signalling system and microvascular endothelial cell response to hypoxia. 5th Imperial College School of Medicine Symposium “Vascular endothelium: Role in disease pathogenesis and as a therapeutic target”. // London, United Kingdom. – 2002. – P. 18.

14. Nikitenko LL, Smith DM, Bicknell R, Rees MCP. Transcriptional regulation of human CRLR in microvascular endothelial cells. // 676th Biochemical Society Meeting, Heriot-Watt University, Edinburgh, United Kingdom. – 2002. – P. 81.

15. Nikitenko LL, Smith DM, Bicknell R, Rees MCP. Transcriptional regulation of the CRLR gene in human microvascular endothelial cells by hypoxia. // The FASEB Journal. – Vol. 17(11). – P. 1499-501. Full-length article is available at: http://www.fasebj.org/cgi/reprint/02-0993fjev1.pdf

16. Nikitenko LL. Molecular mechanisms of the adaptive response of endothelial cells to hypoxia. // 6th International Engelhardt Conference on Molecular Biology, Москва и Санкт Петербург, Российская Федерация. – 2003. – P. 17.

17. Nikitenko LL, Smith DM, Bicknell R, Rees MCP. Mechanisms of transcriptional regulation of GPCR CRLR in the microvasculature. // Special FEBS 2003 Meeting on Signal Transduction, Brussels, Belgium. EJB The FEBS Journal. 2003. - Vol. 270(1). - P. 49.

18. Patel S, Nikitenko LL, Terret J, Bicknell R. Identification of hypoxia inducible messengers expressed in human dermal microvascular endothelial cells. // The 40th American Association for Cancer Research Annual Meeting, New Orleans, USA. – 2003. – P. 270.

19. Wilson CR, Nikitenko LL, Sargent IL, Rees MCP. Adrenomedullin: multiple functions in human pregnancy. // Angiogenesis. – 2004. – Vol. 7(3). – P. 203-12.

20. Nikitenko LL. Heterogeneity of novel CRLR transcripts in human microvascular endothelial cells. Joint International Symposium on CGRP, Amylin and Calcitonin 4th Symposium on Adrenomedullin and Proadrenomedullin N-20 Peptide, Zurich, Switzerland. – 2004. – P. 21.

21. Pathak H, Staff AC., Harsem NK, Braekke K, Sargent I, Rees MCP, and Nikitenko LL. Adrenomedullin expression in the decidua in normal and pre-eclamptic pregnancy. XXXIV Congress of Nordic Federation of Obstetrics of Obstetrics and Gynaecology, Helsinki, Finland. – 2004. – P. 58.

22. Carroll VA, Nikitenko LL, Bicknell R., Harris AL. Antiangiogenic activity of a domain deletion mutant of tissue plasminogen activator containing kringle 2. // Arteriosclerosis, Thrombosis and Vascular Biology. – 2004. – Vol. 25(4). – P. 736-41.

23. Nikitenko L.L. Embryonic development: Tutorials for biomedical students. // Collection MCQ. Keble College, Oxford, United Kingdom. – 2005. – 24 P.

24. Wilson J, Pathak H, Staff AC, Harsem NK, Braekke K, Rees MCP, Sargent IL, Nikitenko LL. Expression of adrenomedullin and its receptor in third trimester placental bed decidua from normal and pre-eclamptic pregnancies. // XI European Placenta Group Meeting, Glasgow, United Kingdom. – 2005. – P. – 72.

25. Nikitenko LL, Blucher N, Fox S, Smith DM, Bicknell R, Rees MCP. Adrenomedullin and CGRP interact with endogenous calcionin-receptor-like receptor in endothelial cells and induce its desensitisation via different mechanisms. // Journal of Cell Science. – 2006. – Vol. 119(5). – P. 910-922.

26. Nikitenko LL, Cross T, Campo L, Leek R, Helen T, Manek S, Bicknell R, Rees MCP. Expression of terminally glycosylated calcitonin receptor-like receptor in uterine leiomyoma: endothelial phenotype and association with microvascular density. // Clinical Cancer Research/ -2006. – Vol. 12(19). – P. 5648-58.

27. Nikitenko LL, Fox S, Kehoe S, Rees MCP, Bicknell R. Adrenomedullin and tumour angiogenesis. // British Journal of Cancer. – 2006. – Vol. 94. – P. 1-7.

28. Nikitenko LL, Boshoff C. Endothelial Cells and Cancer. // In: Moncada S, Higgs A. (eds) Handbook of Experimental Pharmacology, The Vascular Endothelium. Springer-Verlag, Berlin Heidelberg. – 2006. – Vol. 176. – P. 637-664.

29. Nikitenko LL, Morrison J, Roseman F, Rees MCP, Kehoe S. Expression of adrenomedullin and terminally glycosylated calcitonin receptor-like receptor in ovarian cancer. // 11th Biennial International Gynecologic Cancer Society Meeting, Santa Monica, CA, USA. – Int. J. Gynecol. Cancer.– 2006. Vol. 16 (Suppl.3). – P. 690.

30. Nikitenko LL, Blucher N, Fox SB, Bicknell R, Smith DM, Rees M. Adrenomedullin and CGRP interact with endogenous calcitonin receptor-like receptor in microvascular endothelial cells and induce its desensitization via two different mechanisms.// The 24th European Conference on Microcirculation. From Vascular Biology to Clinical Microcirculation, Amsterdam, Netherlands. -2006. - P43.

31. Nikitenko LL, Blucher N, Fox SB, Bicknell R, Smith DM, Rees M. Desensitisation of endogenous calcitonin receptor-like receptor in human microvascular endothelial cells. The 21st Scientific Meeting of the International Society of Hypertension (ISH2006), Fukuoka, Japan. – 2006. – P. 153.

32. Fliss P, Vart R, Trotter M, Boshoff C, Nikitenko LL. Calcitonin receptor-like receptor is upregulated in Kaposi’s sarcoma. The 9th International Workshop on Kaposi’s Sarcoma Associated Herpesvirus (KSHV) and Related Agents, Hyannis, USA. – 2006. – P. 64.

33. Nikitenko LL, Blucher N, Fox SB, Bicknell R, Smith DM, Rees M. Adrenomedullin and CGRP interact with endogenous calcitonin receptor-like receptor in microvascular endothelial cells and induce its desensitization via two different mechanisms.// Abstracts of The Physiological Society 2006 Main Meeting, University College London, London, United Kingdom. – 2006. – P. 80.

34. Vart R, Nikitenko LL, Lagos D, Trotter M, Boshoff C. Viral CPCR and FLIP upregulate angiopoietin-2 expression in lymphatic endothelium via MAPK pathway. The 9th International Workshop on Kaposi’s Sarcoma Associated Herpesvirus (KSHV) and Related Agents, Cape Cod, USA. – 2006. – P. 53.

35. Vart R, Nikitenko LL, Lagos D, Trotter M, Gratrix F, Bourboulia D, Takeuchi Y, Boshoff C. Kaposi’s Sarcoma-associated Herpesvirus encoded vIL6 and vGPCR regulate angiopoietin-2 expression in lymphatic endothelial cells Cancer Research. – 2007. – Vol. 67(9). – P. 4042-51.

36. Nikitenko LL, Generali D, Pellagatti A, Leek R, Rees MCP and Fox S. Upregulation and internalisation of calcitonin-receptor-like receptor in renal cancers. – 2007. – В печати.

37. Ramadass AS, Nikitenko LL, Martianov I, Chow N, Rees MCP, Akoulitchev A. Regulatory switch between distinct chromosomal conformations of active transcriptional units. – 2007. – В печати.

Монография

Никитенко Л.Л. Роль адреномедуллина в биологии эндотелиальной клетки человека. // – М. – ОАО «Издательство Геотар» – 2007. – 147 C.

Патенты оформленные по материалам диссертации

Nikitenko LL, Smith DM, Bicknell R, Rees MCP. Transcriptional Regulation of Therapeutically Useful Gene. // International Patent GO1N 33/50 – 2003.

Akoulitchev A, Ramadass A, Nikitenko LL. Chromosomal conformation footprints in diagnostics of aberrant gene expression. // UK Patent Application No.0603251.0 – 2006.