Israel Hanukoglu

Israel Hanukoglu
Born Istanbul, Turkey
Nationality Israeli
Fields Biochemistry, molecular biology
Institutions Ariel University
Alma mater Hebrew University of Jerusalem
Thesis Mechanism of electron transport to cytochrome P-450 in adrenal cortex mitochondrial monooxygenase systems (1980)
Doctoral advisor Colin Jefcoate
Other academic advisors Neal L. First, David Nelson, W.W. Cleland
Known for Keratin structure, steroidogenic enzymes, Epithelial sodium channels
Notable awards Lindner Prize

Israel Hanukoglu is a Turkish-born Israeli scientist. He is a full professor of biochemistry and molecular biology[1] at Ariel University[2] and former Science and Technology Adviser to the Prime Minister of Israel (1996–1999). He is founder of Israel Science and Technology Homepage.[3]

Education

Israel Hanukoglu received his undergraduate degree cum laude with double majors in biology and psychology and a minor in political science from the Hebrew University of Jerusalem. He then went to the University of Wisconsin-Madison for graduate studies and received his M.Sc. degree in 1976 in Endocrinology-reproductive physiology. His Ph.D. thesis was on the "Mechanism of electron transport to cytochrome P-450 in adrenal cortex mitochondrial steroid monooxygenase systems" under the supervision of Colin R. Jefcoate.

Contributions to science

Hanukoglu was awarded the first Hans Lindner Prize[4] (1988) of the Israel Endocrine Society, and Lubell Award [5] (1991) of the Weizmann Institute of Science for his elucidation of the structures of NAD/NADP coenzyme binding enzyme families, and his discovery of common NADP binding motifs in the structure of these enzymes.[6] The importance of the motifs he identified was confirmed by re-engineering of coenzyme specificities of enzymes.[7]

Hanukoglu's career in molecular biology started at the Department of Biochemistry of the University of Chicago (1980-1983 with Elaine Fuchs), where he cloned and sequenced cDNAs coding for cytoskeleton proteins, actin and alpha keratins. He elucidated the first structures of cytoskeletal keratin families, and predicted the long helical domains of these proteins.[8][9] By computerized analysis of amino acid sequences he predicted that the central rod domain of intermediate filament proteins is composed of four helical segments separated by three short linker sequences.[9] Later crystallographic studies have confirmed this as a general model for intermediate filament protein structure.[10]

In later studies he applied molecular biology techniques to understand the structure and function of mitochondrial enzymes involved in steroid hormone biosynthesis. He cloned the first gene for adrenodoxin reductase, the electron transfer protein of the mitochondrial P450 systems.[6][11][12] This enzyme directs electrons from NADPH to P450scc that is the cholesterol side-chain cleavage enzyme that catalyzes the regulatory step of steroid hormone synthesis in all steroidogenic tissues, and also to steroid 11-beta-hydroxylase (P450c11β) in the adrenal cortex.[12]

His award winning research on the structure of adrenodoxin reductase led to his discovery of motifs that are commonly observed in hundreds of enzymes.[6] His other work in this field includes elucidation of the mechanism of action of hormones in regulating steroid hormone synthesis in adrenal cortex,[13] and the cloning and elucidation of the structure of ACTH receptor.[14]

In his current work with his brother Prof. Aaron Hanukoglu (Tel Aviv University, Sackler Medical School and Wolfson Hospital), he studies the molecular genetics and structure and function of epithelial sodium channel (ENaC). They were the first to identify that mutations in ENaC subunits result in the hereditary disease of pseudohypoaldosteronism type I.[15][16][17][18] These studies also helped establish that ENaC is the principal channel involved in blood volume and blood pressure regulation in humans.

In recent research, Hanukoglu's laboratory has generated polyclonal antibodies against extracellular ENaC subunits. These antibodies for the first time permitted visualization of intracellular localization of ENaC at high resolution and led to the discovery that in all cells with motile cilia ENaC is located on cilia.[19] These studies establish that ENaC is an important regulator of fluid level in the luminal side of cells with motile cilia in the reproductive and respiratory tract.[19]

He organized the first International Symposium in Molecular Steroidogenesis in Jerusalem in 1991 which served as the cornerstone for a continuing series of international Symposia gathering scientists who specialize in this field.[20]

In 2003 Hanukoglu founded Israel's first Molecular Biology B.Sc. degree program in the Ariel University Center of Samaria[21] and served as the Chairman of the Molecular Biology Department there from 2003 to 2008.[22]

Civic activities

Besides a scientific career Hanukoglu has maintained an active academic and civic leadership role. In 1995 he was elected as the Chairman of the Professors for a Strong Israel, a self-described "non-partisan organization of academics united by a shared concern for the security and the Jewish character of the State of Israel." From 1996 to 1999 he served as the Science Adviser to the Prime Minister of Israel Benjamin Netanyahu. In 2003 he was appointed as the scientific adviser to the Mayor of Rishon-Lezion for establishing the Jewish Nobel Prize Laureate Boulevard Outdoor Museum. Since 1996 he has served as a founding member of the Ariel Center for Policy Research executive board.[22]

Hanukoglu contested the 2003 Knesset elections as the tenth-placed candidate on the Herut – The National Movement list.[23] However, the party failed to win a seat.

References

  1. ↑ http://www.inn.co.il/Besheva/Article.aspx/1541
  2. ↑ http://www.ariel.ac.il/projects/trp/GeneralInformation.asp?numRec=16
  3. ↑ http://www.science.co.il/About.php
  4. ↑ http://www.ies.org.il/hovers_lindner.pdf
  5. ↑ http://www.weizmann.ac.il/acadaff/past_prize_SC.pdf
  6. ↑ 6.0 6.1 6.2 Hanukoglu, I.; Gutfinger, T. (Mar 1989). "cDNA sequence of adrenodoxin reductase. Identification of NADP-binding sites in oxidoreductases.". Eur J Biochem 180 (2): 479–84. doi:10.1111/j.1432-1033.1989.tb14671.x. PMID 2924777.
  7. ↑ Scrutton NS, Berry A, Perham RN (January 1990). "Redesign of the coenzyme specificity of a dehydrogenase by protein engineering.". Nature 343 (6253): 38–43. doi:10.1038/343038a0. PMID 2296288.
  8. ↑ Hanukoglu I, Fuchs E (November 1982). "The cDNA sequence of a human epidermal keratin: divergence of sequence but conservation of structure among intermediate filament proteins". Cell 31 (1): 243–252. doi:10.1016/0092-8674(82)90424-X. PMID 6186381.
  9. ↑ 9.0 9.1 Hanukoglu I, Fuchs E (July 1983). "The cDNA sequence of a human epidermal keratin: divergence of sequence but conservation of structure among intermediate filament proteins". Cell 33 (3): 915–924. doi:10.1016/0092-8674(83)90034-X. PMID 6191871.
  10. ↑ Lee CH, Kim MS, Chung BM, Leahy DJ, Coulombe PA. (June 2012). "Structural basis for heteromeric assembly and perinuclear organization of keratin filaments.". Nat Struct Mol Biol 19 (7): 707–15. doi:10.1038/nsmb.2330. PMID 22705788.
  11. ↑ Hanukoglu I, Gutfinger T, Haniu M, Shively JE (December 1987). "Isolation of a cDNA for adrenodoxin reductase (ferredoxin-NADP+ reductase). Implications for mitochondrial cytochrome P-450 systems". Eur J Biochem 169 (3): 449–455. doi:10.1111/j.1432-1033.1987.tb13632.x. PMID 3691502.
  12. ↑ 12.0 12.1 Hanukoglu I (December 1992). "Steroidogenic enzymes: structure, function, and role in regulation of steroid hormone biosynthesis". J Steroid Biochem Mol Biol 43 (8): 779–804. doi:10.1016/0960-0760(92)90307-5. PMID 22217824.
  13. ↑ Hanukoglu I, Feuchtwanger R, Hanukoglu A (Nov 1990). "Mechanism of corticotropin and cAMP induction of mitochondrial cytochrome P450 system enzymes in adrenal cortex cells.". J Biol Chem 265 (33): 20602–8. PMID 2173715.
  14. ↑ Raikhinstein, M.; Zohar, M.; Hanukoglu, I. (Feb 1994). "cDNA cloning and sequence analysis of the bovine adrenocorticotropic hormone (ACTH) receptor.". Biochim Biophys Acta 1220 (3): 329–32. doi:10.1016/0167-4889(94)90157-0. PMID 8305507.
  15. ↑ Strautnieks, SS.; Thompson, RJ.; Hanukoglu, A.; Dillon, MJ.; Hanukoglu, I.; Kuhnle, U.; Seckl, J.; Gardiner, RM.; Chung, E. (Feb 1996). "Localisation of pseudohypoaldosteronism genes to chromosome 16p12.2-13.11 and 12p13.1-pter by homozygosity mapping.". Hum Mol Genet 5 (2): 293–9. doi:10.1093/hmg/5.2.293. PMID 8824886.
  16. ↑ Chang, SS.; Grunder, S.; Hanukoglu, A.; Rösler, A.; Mathew, PM.; Hanukoglu, I.; Schild, L.; Lu, Y.; Shimkets, RA.; Nelson-Williams, C.; Rossier, BC.; Lifton, RP. (Mar 1996). "Mutations in subunits of the epithelial sodium channel cause salt wasting with hyperkalaemic acidosis, pseudohypoaldosteronism type 1.". Nat Genet 12 (3): 248–53. doi:10.1038/ng0396-248. PMID 8589714.
  17. ↑ Saxena, A.; Hanukoglu, I.; Saxena, D.; Thompson, RJ.; Gardiner, RM.; Hanukoglu, A. (Jul 2002). "Novel mutations responsible for autosomal recessive multisystem pseudohypoaldosteronism and sequence variants in epithelial sodium channel alpha-, beta-, and gamma-subunit genes.". J Clin Endocrinol Metab 87 (7): 3344–50. doi:10.1210/jc.87.7.3344. PMID 12107247.
  18. ↑ Edelheit, O.; Hanukoglu, I.; Gizewska, M.; Kandemir, N.; Tenenbaum-Rakover, Y.; Yurdakök, M.; Zajaczek, S.; Hanukoglu, A. (May 2005). "Novel mutations in epithelial sodium channel (ENaC) subunit genes and phenotypic expression of multisystem pseudohypoaldosteronism.". Clin Endocrinol (Oxf) 62 (5): 547–53. doi:10.1111/j.1365-2265.2005.02255.x. PMID 15853823.
  19. ↑ 19.0 19.1 Enuka, Y.; Hanukoglu, I.; Edelheit, O.; Vaknine, H.; Hanukoglu, A. (Mar 2012). "Epithelial sodium channels (ENaC) are uniformly distributed on motile cilia in the oviduct and the respiratory airways.". Histochem Cell Biol 137 (3): 339–53. doi:10.1007/s00418-011-0904-1. PMID 22207244.
  20. ↑ Hanukoglu, I. (Dec 1992). "Current research on steroid metabolism: transition from biochemistry to molecular-cell biology.". J Steroid Biochem Mol Biol 43 (8): 745–9. doi:10.1016/0960-0760(92)90304-2. PMID 22217821.
  21. ↑ Israel Hanukoglu. Brief Biography
  22. ↑ 22.0 22.1 Israel Hanukoglu. Curriculum Vitae
  23. ↑ Candidates for the 16th Knesset Israel Ministry of Foreign Affairs

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