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Fund for investing in fundamental research
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Research Units
- Libera Universita' "Vita Salute S.Raffaele" MILANO
Dip. MEDICINA E CHIRURGIA , MILANO (MI) - Universita' degli Studi di MILANO
Dip. SCIENZE E TECNOLOGIE BIOMEDICHE , MILANO (MI) - ISTITUTO DERMOPATICO DELL'IMMACOLATA (IRCCS)
Laboratorio di Patologia Vascolare , ROMA (RM) - Universita' degli Studi di SASSARI
Ist. Clinica medica generale e terapia medica , SASSARI (SS) - Universita' degli Studi di NAPOLI "Federico II"
Dip. MEDICINA CLINICA E SPERIMENTALE , NAPOLI (NA) - CONSORZIO MARIO NEGRI SUD
Dipartimento di Biologia Cellulare ed Oncologia , CHIETI (CH) - Universita' degli Studi di CATANZARO
Dip. MEDICINA SPERIMENTALE E CLINICA , CATANZARO (CZ)
Similar FIRB:
- 1 - Apoptotic mechanisms and their implications in human diseases
- 2 - Development of innovative molecules for the treatment of neurodegenerative and neuroinflammatory disease
- 3 - Molecular recognition and cell function
- 4 - The ubiquitous Ca2+ signalling cascade: from molecules to functions
- 5 - Identification of new molecular markers for renal carcinoma by the application of genomic and proteomic technologies.
- 6 - Mechanisms regulating nervous system development and neural differentiation (PRONEURO)
- 7 - Metabolism and organization of sphingolipids in cell neurodegeneration models: understanding of the basic molecular mechanisms and development of novel therapeutical strategies.
- 8 - HOST-TUMOR BALANCE IN THE THERAPY OF NEOPLASIAS: ROLE OF NF-kB
- 9 - NEURODEGENERATIVE DISEASES AS A RESULT OF AN ALTERED PROCESSING OF NEURONAL PROTEINS. ANIMAL AND IN VITRO CULTURED MODELS.
- 10 - Deciphering cell identity and cell differentiation mechanisms in the postgenomic era by using three paradigmatic systems: breast, bone and lymphocytes
Scientific and education field classification
International Patent Classification
- CHEMISTRY; METALLURGY
- BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- MEASURING OR TESTING PROCESSES INVOLVING ENZYMES OR MICRO-ORGANISMS (immunoassay G01N33/53); COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
- MICRO-ORGANISMS OR ENZYMES; COMPOSITIONS THEREOF (biocides, pest repellants or attractants, or plant growth regulators, containing micro-organisms, viruses, microbial fungi, enzymes, fermentates or substances produced by or extracted from micro-organisms or animal material A01N63/00; food compositions A21, A23; medicinal preparations A61K; chemical aspects of, or use of materials for, bandages, dressings, absorbent pads or surgical articles A61L; fertilisers C05); PROPAGATING, PRESERVING OR MAINTAINING MICRO-ORGANISMS (preservation of living parts of humans or animals A01N1/02); MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA (micro-biological testing media C12Q)
- BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
Geographical classification
- Region: Lombardia
Bibliografia
1. Whelton P.K. et al Textbook of hypertension ed. by Swales J.D. 1994;1:11-21.2. Hamet P. et al J Hypertens 1998;16:397-418.
3. Holtzman N.A. et al New Engl J Med 2000;343(2):141-144.
4. Luft FC. Molecular genetics of hypertension Edited by A.F. Dominiczack A.F., Connell J.M.C. and Soubrier F. 1999;12:245-257.
5. Terwilliger J.D. et al Hum Biol 2000;72:63-132.
6. Schork N. et al ed Domikzack A., Connel J.M.., Soubrier F: Bios S.P.1999;9.
7. Levy D. et al Hypertension 2000;36:477-483.
8 Barlassina C, et al. Kidney Int 2000; 57/3: 1083-1090
9. Staessen J.,et al J Hypertens 2001;19:1349-1358.
10. Wolf U. Hum Genet 1997;100:305-321
11. Scriver C. et al TIG 1999;15:267-272.
12. Weatherall D.J. Nature reviews 2001;2:245-255.
13. Morris B.Progress in Hypertension 1999;4:1-44.
14. Corvol P. et al 1999;33:1324-1331.
15. Blackstock W.P. et al Trends Biotechnol 1999;17:121-127.
16. Verey F. Am J Physiol 1999;46:F319-F327
17. Julier C. et al Hum Mol Genet 1997;6:2077-2085.
18. Baima J. et al Hypertension 1999;34:4-7.
19. BIANCHI G, et al. Clin Sci 1970; 38: 741-766
20. BIANCHI G, ET AL. Clin Sci 1972; 42: 651-664
21. CARAVAGGI AM,ET AL Circ Res 1976; 38: 315-321
22 BIANCHI G, ET AL. Clin Sci Mol Med 1973; 45 (suppl I): 135s-139s
23. BIANCHI G, ET AL Clin Sci Mol Med 1974; 47: 435-448
24. GUIDI E, et al Nephron 1985; 41: 14-21
25. GUIDI E, et al Journal of American Society of Nephrology 1996; 7: 1131-1138
26. BIANCHI G, et al Lancet 1979; I: 173-177
27. BIANCHI G, et al Kidney Int 1983; 23: 870-875
28. BIANCHI G, ET AL Circ Res 1975; 36&37 (suppl I): I153-I161
29. BAER PG, et al. Kidney Intern 1978; 13: 452-466
30. FERRARI P, et al Hypertension 1987; 10 (suppl I): I-32/I-36
31. BIANCHI G, et al Hypertension 1985; 7: 319-325
32. PARENTI P, et al Hypertension 1986; 8: 932-939
33. FERRARI P, et al J of Hypertension 1986; 4 (suppl 6): S379-S381
34. CUSI D, et al J Hum Hypertension 1990; 4: 307-311
35. CUSI D, ET AL J Hypertension 1987; 5(suppl 5): S255-S256
36. SALARDI S, ET AL American J Hypertens 1989; 2, 229
37. BIANCHI G, et al Proc Natl Acad Sci 1994; 91: 3999-4003
38. CUSI D, et alThe Lancet 1997; 349: 1353-1357
39. Matsuoka Y.Cell Mol Life Sci 2000;57(6):884-895.
40. 1 Bennett V. Physiol. Rev. 70:1029-1065, 1990.
41 Hughes CA, et al. J.Biol.Chem. 1995,270:18990-18996.
42 Kuhlman PA, et al J. Biol. Chem. 1996,271:7986-7991.
43 Gardner K., et al. J. Biol. Chem. 1986, 261:1339-1348.
44 Fukata Y, et al J Cell Biol. 1999 Apr 19;145(2):347-61.
45 Kurana S. . J Membrane Biol 2000;178:73-87.
46 Tripodi G.,Biochem. Biophis. Res. Com. 1997,237:685-689.
47 Zagato L, et al. Hypertension. 2000 Nov;36(5):734-9.
48. Tripodi G, et al J Clin Invest 1996,97:2815-2822.
49. Halushka MK, et al Nat Genet. 1999 Jul;22(3):239-47.
50. Bianchi G, et al. Am J Hypertens. 2000 Jun;13(6 Pt 1):739-43.
51. BARLASSINA C.Kidney Int.2000;57/3:1083-1090.
52. MANUNTA P, et Hypertension 33:694-697,1999
53. GLORIOSO N, et al Hypertension 34: 649-654,1999
54. Casari, G.,et al Hypertension 1995,25:326-326.
55 Busjajn A., et al. J Hypertens 1999,17:1437-1441.
56. Bray M., et al J Hypertens 1999,17
57 Niu T., et al Hypertension 1999,33:1332-1337.
58. FERRANDI M, et al Am J Physiol 277:H1338-H1349,1999
59. Krmar F., et al J Am Soc Nephrol 2001;12:58A.
60 Torielli L., et al ESF-EMBO Workshop 2001.
61 Salardi S.,et al . ECF 2001.
62. Tripodi G.,et al . J MomlMed 2000,79(2-3):B30.
63 Marro ML, et al Hypertension. 2000 Sep;36(3):449-53.
64. Balkestein E., et al Hypertension 2001;38.
65 Wang JG., et al Am J Kidney Disease 2001;6.
66. Wang J.G. Eur J Pharmacol 2001;410:289-302.
67. Ueda S. Hypertension 1995;25:1266-1269.
68. Velden V. J Biol Chem 1995;270 (48):28962-28969.
69. Kizhakkekara R. secretion. J Biol Chem 2000;275(30):23253-23258.
70. Kupari M. Circulation 1998;97:569-575.
71. Brand E. Hypertension 1998;32:198-204.
Keywords
hypertension; adducin; organ complications; protein interactions; functinal genomics; intermediate phenotypesIdentification and validation of genetic-molecular mechanisms involved in tubular renal sodium transport in hypertension and associated organ complication
Libera Università "Vita Salute S. Raffaele" - MilanoAbstract
The present proposal coheres to the more general theme "IDENTIFICATION OF THE MOLECULAR ALTERATIONS INVOLVED IN/OR ASSOCIATED TO THE PATHOGENESIS AND DEVELOPMENT OF COMMON AND RARE DISEASES" within the strategic program "POST-GENOME".Arterial hypertension affects at least 20% of adult population of western countries and its cardiovascular and renal complications are one one of the major source of costs of National Health Care systems.
The present proposal has been developed with the following aims:
1) validation of the molecular mechanisms of the involvement of alpha-adducin (ADD1), ACE and aldosterone synthase (CYP11B2) genes in the development of hypertension and cardiovascular complications that we have recently reported.
2) establishment of the association between genotypes and some intermediate phenotypes relevant to the clinical symptoms with functional genomic studies.
3) identification of the sequence of molecular events going from the primary genetic mechanism to the secondary ones causing the cellular and organ functional abnormalities responsible for the clinical phenotypes, i.e. hypertension, cardiovascular and renal complications.
The choice of these three primary molecular mechanisms is based on:
1) statistical genetic studies on ADD1 recently summarised (Bianchi G & Cusi D, Am J Hypertens 2000;13:739 -43)
2) observation that the lack of association of 460Trp allele of ADD1 to>>>
Principal Investigator
GIUSEPPE BIANCHI, Libera Universita' "Vita Salute S.Raffaele" MILANOResearch Goal
This project is part of the research field aimed at defining the genetic-molecular mechanisms underlying poligenic and multifactorial diseases with high social impact such as essential hypertension and related organ complications.The main aim of this project is to define and validate from the genetic, biochemical and functional point of view the molecular alterations of some proteins regulating the renal Na handling involved in essential hypertension causes and related complications.
The strategy adopted to pursue this goal is based on the currently achieved pathophysiological know-how that allows to define the primary biochemical alteration and other new molecular mechanisms that are associated to the primary one and modulate it.
In details, this strategy provides for: a) to define a biochemical and cellular mechanism associated to the disease; in this case represented by the ion transport across the cell membrane; b) to detect which proteins, among those involved in ion transport regulation, are structurally and functionally different between affected and not affected subjects, using also animal models of the human disease; c) to establish if there are polymorphisms in the gene coding for such a protein that are associated to the human and animal disease.
The possibility that a strategy based on the "candidate gene" hypothesis may be wrong or applies only to a small portion of patients is part of the risk of genomic research. Other>>>
