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Israel Hanukoglu

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257:), where he cloned and sequenced cDNAs coding for cytoskeletal proteins, actin and alpha keratins. He elucidated the first structures of cytoskeletal keratin families, and predicted the long helical domains of these proteins. 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. Later crystallographic studies have confirmed this as a general model for intermediate filament protein structure. 360:
skin and epidermal appendages, they found a widespread distribution of ENaC in keratinocytes in the epidermal layers. Yet, in the eccrine sweat glands, ENaC was localized on the apical cell membrane exposed to the duct of these sweat glands. Based on additional observations, they concluded that the ENaC located on the eccrine gland sweat ducts is responsible for the uptake of Na ions from sweat secretions. This recycling of Na reduces the concentration of salt in perspiration and prevents the loss of salt at hot climates via
292:, but the NADPH binding site has a different consensus sequence that could be responsible for NAD vs. NADP coenzyme specificity. The importance of the motifs he identified was confirmed by re-engineering of coenzyme specificities of different enzymes. Elucidation of the crystal structure of adrenodoxin reductase further verified Israel's identification of the coenzyme binding sites. Analysis of the phylogeny of this enzyme in eukaryotes showed that the NADP binding site sequence is strictly conserved. 356:
discovery that in all cells with motile cilia ENaC is located on cilia. These studies establish that ENaC is an important regulator of fluid level in the luminal side of cells with motile cilia in the female reproductive and respiratory tract. More recently, they showed that these sodium channels are also located in the seminiferous tubules in the testis and in the tail and head region of sperm.
273:) via an electron-transfer chain that includes two additional proteins. These proteins are located on the inner mitochondrial membrane. Israel reconstituted this system using proteins he purified, characterized the process of electron transfer between the proteins, and built a kinetic model that simulated precisely the dynamic behavior of this complex system. 326:, Sackler Medical School and E. Wolfson Medical Center), identified that a hereditary disease named pseudohypoaldosteronism (PHA) type I encompasses two independent syndromes. Following this discovery the two brothers continued their collaboration to understand the molecular basis of the severe form of PHA. 232:
for graduate studies and received his M.Sc. degree in 1976 in an inter-disciplinary Endocrinology-Reproductive physiology program, under the joint supervision of Prof. Harry J. Karavolas (Dept. of Physiological Chemistry) and Prof. Robert W. Goy (Dept. of Psychology). His Ph.D. thesis research on the
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Systemic pseudohypoaldosteronism patients with mutated ENaC subunits may lose significant amount salt in sweat especially at hot climates. To identify the sites of salt loss, Hanukoglu brothers examined the localization of ENaC in the human skin. In a comprehensive study examining all the layers of
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As the steroidogenic tissues have very high levels of antioxidants, Israel suspected that the P450 systems may leak electrons producing oxygen radicals. He examined this issue and showed that indeed, electrons that leak during the action mitochondrial P450 systems generate reactive oxygen species.
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Besides a scientific career, Hanukoglu has maintained an active academic and civic leadership role. In 2003, Hanukoglu founded Israel's first B.Sc. degree program in Molecular Biology at the Ariel University Center. He served as the Chairman of the Molecular Biology Department from 2003 to 2008.
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To define the sites of localization of ENaC in tissues and within cells, Hanukoglu's laboratory 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
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Following these studies, the Hanukoglu brothers directed their attention to understand the structure and function of ENaC assembled from normal and mutated subunits. Their analyses showed that the phenotypic variations in the severity of pseudohypoaldosteronism are associated with the types of
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Hanukoglu's website, the Israel Science and Technology Homepage, had included a page captioned, "Long-Form Birth Certificate of Obama is a Forged Document." The analyses presented asserted that "without a doubt that the Long-Form Birth Certificate of Mr. Obama is a fabricated, fake and forged
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Hanukoglu has been an editorial board member/Associate editor in five journals, including Biochemistry and Molecular Biology Education, BMC Biotechnology, Cells, Frontiers in Renal and Epithelial Physiology, and Gene. In 2018, he received Publons Peer Review Award for placing in the top 1% of
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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 (March 1996). "Mutations in subunits of the epithelial sodium channel cause salt wasting with hyperkalaemic acidosis, pseudohypoaldosteronism type 1".
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By sequence and structural analyses of adrenodoxin reductase, Israel identified its binding sites for the electron donor and acceptor coenzymes, NADPH and FAD. By sequence analyses of the large oxidoreductase type of enzyme families, he noted that the FAD-binding site is a classical
280:, he first determined the molar stoichiometry of the mitochondrial P450 system proteins using specific antibodies that he generated. He then set out to clone the cDNAs and the genes that code for these enzymes. His lab was the first to clone the cDNAs and the gene coding for 1831:
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".
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Hanukoglu A, Edelheit O, Shriki Y, Gizewska M, Dascal N, Hanukoglu I (September 2008). "Renin-aldosterone response, urinary Na/K ratio and growth in pseudohypoaldosteronism patients with mutations in epithelial sodium channel (ENaC) subunit genes".
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Edelheit O, Hanukoglu I, Shriki Y, Tfilin M, Dascal N, Gillis D, Hanukoglu A (March 2010). "Truncated beta epithelial sodium channel (ENaC) subunits responsible for multi-system pseudohypoaldosteronism support partial activity of ENaC".
439:, 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 233:"Mechanism of electron transport to cytochrome P-450 in adrenal cortex mitochondrial steroid monooxygenase systems" was carried out under the supervision of Prof. Colin R. Jefcoate. He received his Ph.D. diploma in August 1980. 2012:
Edelheit O, Hanukoglu I, Dascal N, Hanukoglu A (April 2011). "Identification of the roles of conserved charged residues in the extracellular domain of an epithelial sodium channel (ENaC) subunit by alanine mutagenesis".
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genetic mutations. Their work on the structure of ENaC subunits led to the identification of charged residues and regions responsible for transport of the protein to membrane and for regulation of extracellular Na ions.
341:) that encode for protein subunits of the Epithelial sodium (Na) channel (ENaC). These studies also helped establish that ENaC is the principal channel involved in blood volume and blood pressure regulation in humans. 269:
in all steroidogenic tissues, including the adrenal cortex, and the reproductive organs. The first step of steroidogenesis is dependent on the transfer of electrons from NADPH to a P450 type enzyme (
303:) in regulating steroid hormone synthesis in the adrenal cortex, regulation of adrenal steroidogenic capacity in disease states, and the cloning and elucidation of the structure of ACTH receptor. 2155:
Enuka Y, Hanukoglu I, Edelheit O, Vaknine H, Hanukoglu A (March 2012). "Epithelial sodium channels (ENaC) are uniformly distributed on motile cilia in the oviduct and the respiratory airways".
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By their collaborative work that also included additional labs, the Hanukoglu brothers discovered that the severe forms of pseudohypoaldosteronism type I result from mutations in three genes (
954:"Stoichiometry of mitochondrial cytochromes P-450, adrenodoxin and adrenodoxin reductase in adrenal cortex and corpus luteum. Implications for membrane organization and gene regulation" 196:
in Istanbul until the end of junior high school. In ninth grade, he switched to Atatürk Erkek Lisesi in Taksim, Istanbul, graduating in 1969. In his senior year, he was selected for an
1792:"Novel mutations responsible for autosomal recessive multisystem pseudohypoaldosteronism and sequence variants in epithelial sodium channel alpha-, beta-, and gamma-subunit genes" 2198:
Sharma S, Hanukoglu A, Hanukoglu I (2018). "Localization of epithelial sodium channel (ENaC) and CFTR in the germinal epithelium of the testis, Sertoli cells, and spermatozoa".
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Ziegler GA, Vonrhein C, Hanukoglu I, Schulz GE (Jun 1999). "The structure of adrenodoxin reductase of mitochondrial P450 systems: electron transfer for steroid biosynthesis".
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In addition to the personal prizes above, the research presentations from the laboratory of Prof. Hanukoglu received four awards at national and international meetings.
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Hanukoglu A, Fried D, Nakash I, Hanukoglu I (Nov 1995). "Selective increases in adrenal steroidogenic capacity during acute respiratory disease in infants".
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Hanukoglu I, Tanese N, Fuchs E (Feb 1983). "Complementary DNA sequence of a human cytoplasmic actin. Interspecies divergence of 3' non-coding regions".
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Hanukoglu I (2017). "Conservation of the Enzyme-Coenzyme Interfaces in FAD and NADP Binding Adrenodoxin Reductase-A Ubiquitous Enzyme".
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in 1991 which served as the cornerstone for a continuing series of international symposia for scientists who specialize in this field.
2482: 2477: 2437: 2432: 995:"Isolation of a cDNA for adrenodoxin reductase (ferredoxin-NADP+ reductase). Implications for mitochondrial cytochrome P-450 systems" 444: 2517: 2502: 2371: 2351: 1080:"Human adrenodoxin reductase: two mRNAs encoded by a single gene on chromosome 17cen----q25 are expressed in steroidogenic tissues" 1276:"Electron leakage from the mitochondrial NADPH-adrenodoxin reductase-adrenodoxin-P450scc (cholesterol side chain cleavage) system" 861:"Induction and mitochondrial localization of cytochrome P450scc system enzymes in normal and transformed ovarian granulosa cells" 1877:"Epithelial sodium channel (ENaC) family: Phylogeny, structure-function, tissue distribution, and associated inherited diseases" 1137:
Scrutton NS, Berry A, Perham RN (Jan 1990). "Redesign of the coenzyme specificity of a dehydrogenase by protein engineering".
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During his Ph.D. thesis research, Israel isolated the mitochondrial enzymes that catalyze the first step in the synthesis of
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Hanukoglu, I. (Dec 1992). "Current research on steroid metabolism: transition from biochemistry to molecular-cell biology".
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Strautnieks SS, Thompson RJ, Hanukoglu A, Dillon MJ, Hanukoglu I, Kuhnle U, Seckl J, Gardiner RM, Chung E (February 1996).
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His studies also showed that in bovine ovary, levels of antioxidants are coordinately regulated with steroidogenesis.
201: 625:"The cDNA sequence of a Type II cytoskeletal keratin reveals constant and variable structural domains among keratins" 1707:"Localisation of pseudohypoaldosteronism genes to chromosome 16p12.2-13.11 and 12p13.1-pter by homozygosity mapping" 458:. For 12 years (1996–2008), he served as a founding member of the Ariel Center for Policy Research executive board. 1401:"Antioxidant capacity is correlated with steroidogenic status of the corpus luteum during the bovine estrous cycle" 1315:"Electron leakage from the adrenal cortex mitochondrial P450scc and P450c11 systems: NADPH and steroid dependence" 348:
In an extensive review of studies on ASIC and ENaC, Prof. Hanukoglu has summarized the major similarities between
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National Cancer Institute, National Research Service Award for Postdoctoral Fellowship in Biochemistry (1982).
2107:"ASIC and ENaC type sodium channels: Conformational states and the structures of the ion selectivity filters" 1481:"Mitochondrial-genome-encoded RNAs: differential regulation by corticotropin in bovine adrenocortical cells" 193: 2487: 373: 197: 97:
Mechanism of electron transport to cytochrome P-450 in adrenal cortex mitochondrial monooxygenase systems
2246:"Expression of epithelial sodium channel (ENaC) and CFTR in the human epidermis and epidermal appendages" 407:
2016 Sentinel of Science Award for peer review in Biochemistry, Genetics and Molecular Biology by Publons
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2018 Publons Peer Review Award. Ranked in the top 1% of reviewers in "Molecular Biology and Genetics".
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Crystal Structure of NADP binding enzyme that details the structural properties of NADP binding motif
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In this field, Israel organized the first International Symposium in Molecular Steroidogenesis in
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Solish SB, Picado-Leonard J, Morel Y, Kuhn RW, Mohandas TK, Hanukoglu I, Miller WL (Oct 1988).
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His other work in this field includes elucidation of the mechanism of action of corticotropin (
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Lubell Prize for the outstanding young scientist at the Weizmann Institute of Science (1991).
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Tsueng G, Good BM, Ping P, Golemis E, Hanukoglu I, van Wijnen AJ, Su AI (5 November 2016).
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Hanukoglu's career in molecular biology started at the Department of Biochemistry of the
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Prof. Hanukoglu's scientific work concentrated in three different areas outlined below.
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with double majors in biology and psychology and a minor in political science from the
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Hanukoglu I, Boggula VR, Vaknine H, Sharma S, Kleyman T, Hanukoglu A (January 2017).
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Saxena A, Hanukoglu I, Saxena D, Thompson RJ, Gardiner RM, Hanukoglu A (July 2002).
1567: 1385: 754: 656: 609: 284:- the first enzyme in the electron transfer chain of the mitochondrial P450 system. 2277: 2227: 2091: 1998: 1861: 1776: 1649: 1260: 1174: 910:"Mitochondrial cytochrome P-450scc. Mechanism of electron transport by adrenodoxin" 361: 254: 160: 148: 124: 2042: 845: 909: 2026: 1982: 1938: 1399:
Rapoport R, Sklan D, Wolfenson D, Shaham-Albalancy A, Hanukoglu I (March 1998).
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Delta Research Career Development Award at Weizmann Institute of Science (1987).
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Proceedings of the National Academy of Sciences of the United States of America
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Proceedings of the National Academy of Sciences of the United States of America
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The first Hans Lindner Prize in Endocrinology, Israel Endocrine Society (1988)
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Technion V.P.R. Fund-Henri Gutwirth Award for Excellence in Research (1984).
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Edelheit O, Ben-Shahar R, Dascal N, Hanukoglu A, Hanukoglu I (April 2014).
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reviewers in "Molecular Biology and Genetics" with a global rank of 22nd.
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In his clinical work as an endocrinologist, Israel's older brother, Prof.
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Google Scholar profile of citations of Prof. Hanukoglu's publications
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Hanukoglu I, Spitsberg V, Bumpus JA, Dus KM, Jefcoate CR (May 1981).
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Keratin structure, steroidogenic enzymes, epithelial sodium channels
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In 2003 he was appointed as the scientific advisor to the mayor of
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In his first academic position at the Department of Biology at the
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Hanukoglu I, Suh BS, Himmelhoch S, Amsterdam A (October 1990).
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Biochimica et Biophysica Acta (BBA) - Molecular Cell Research
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Hanukoglu I, Rapoport R, Weiner L, Sklan D (September 1993).
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Lee CH, Kim MS, Chung BM, Leahy DJ, Coulombe PA (Jul 2012).
2372:"Long-Form Birth Certificate of Obama is a Forged Document" 993:
Hanukoglu I, Gutfinger T, Haniu M, Shively JE (Dec 1987).
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International Scholarship (from Turkey to the USA) (1969).
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The Journal of Steroid Biochemistry and Molecular Biology
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The Journal of Steroid Biochemistry and Molecular Biology
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The Journal of Steroid Biochemistry and Molecular Biology
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In 1995, Hanukoglu was elected as the Chairman of the
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Hanukoglu I, Feuchtwanger R, Hanukoglu A (Nov 1990).
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The Journal of Clinical Endocrinology and Metabolism
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The Journal of Clinical Endocrinology and Metabolism
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Israel Science and Technology Directory: About page
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Ford Foundation Fellowship in Endocrinology (1975).
220:Israel Hanukoglu received his undergraduate degree 116: 106: 90: 82: 74: 59: 51: 43: 35: 25: 18: 1313:Rapoport R, Sklan D, Hanukoglu I (10 March 1995). 1661: 1659: 1581:Raikhinstein M, Zohar M, Hanukoglu I (Feb 1994). 1032: 1030: 171:and former science and technology adviser to the 2015:American Journal of Physiology. Renal Physiology 766: 764: 721:"Proteopedia: Coiled-coil structure of keratins" 212:, and received his high-school diploma in 1970. 2150: 2148: 524: 522: 520: 8: 468:Barack Obama citizenship conspiracy theories 15: 2328: 2073: 1900: 1807: 1722: 1514: 1504: 1455: 1113: 1103: 1054: 1010: 969: 928: 884: 788: 736: 695: 676:Nature Structural & Molecular Biology 511:Israel Science and Technology Directory. 2468:Israeli people of Turkish-Jewish descent 1479:Raikhinstein M, Hanukoglu I (Nov 1993). 385:Fellowship Award in Biochemistry (1981). 2408:Home page of Professor Israel Hanukoglu 1875:Hanukoglu I, Hanukoglu A (April 2016). 1319:Archives of Biochemistry and Biophysics 1280:Archives of Biochemistry and Biophysics 481: 383:Damon Runyon Cancer Research Foundation 278:Technion-Israel Institute of Technology 2463:University of Wisconsin–Madison alumni 2458:Hebrew University of Jerusalem alumni 1037:Hanukoglu I, Gutfinger T (Mar 1989). 952:Hanukoglu I, Hanukoglu Z (May 1986). 908:Hanukoglu I, Jefcoate CR (Apr 1980). 7: 409:(1st place among Israeli Scientists) 188:Elementary and high school education 1444:The Journal of Biological Chemistry 917:The Journal of Biological Chemistry 777:The Journal of Biological Chemistry 462:Obama birth certificate controversy 2493:Joseph A. Craig High School alumni 2453:Academic staff of Ariel University 2361:Israel Ministry of Foreign Affairs 1056:10.1111/j.1432-1033.1989.tb14671.x 1012:10.1111/j.1432-1033.1987.tb13632.x 971:10.1111/j.1432-1033.1986.tb09633.x 14: 623:Hanukoglu I, Fuchs E (Jul 1983). 576:Hanukoglu I, Fuchs E (Nov 1982). 1846:10.1111/j.1365-2265.2005.02255.x 1043:European Journal of Biochemistry 999:European Journal of Biochemistry 958:European Journal of Biochemistry 719:Hanukoglu I, Ezra L (Jan 2014). 456:Jewish Nobel Laureates Boulevard 314:Epithelial sodium channel (ENaC) 2523:20th-century Israeli scientists 2513:20th-century Turkish scientists 2508:21st-century Israeli scientists 2498:21st-century Turkish scientists 2352:Candidates for the 16th Knesset 2250:Histochemistry and Cell Biology 2157:Histochemistry and Cell Biology 230:University of Wisconsin–Madison 78:Biochemistry, molecular biology 2200:Journal of Molecular Histology 1225:Journal of Molecular Evolution 437:Professors for a Strong Israel 226:Hebrew University of Jerusalem 47:Hebrew University of Jerusalem 1: 1666:Hanukoglu A (November 1991). 1457:10.1016/S0021-9258(17)30545-8 1417:10.1016/S0304-4165(97)00136-0 930:10.1016/S0021-9258(19)85851-9 790:10.1016/S0021-9258(19)69436-6 445:Herut – The National Movement 423:Academic and civic activities 1634:10.1016/0960-0760(92)90304-2 1599:10.1016/0167-4889(94)90157-0 1190:Journal of Molecular Biology 830:10.1016/0960-0760(92)90307-5 641:10.1016/0092-8674(83)90034-X 594:10.1016/0092-8674(82)90424-X 555:10.1016/0022-2836(83)90117-1 543:Journal of Molecular Biology 493:. Israel National News (INN) 117:Other academic advisors 2473:Turkish emigrants to Israel 2105:Hanukoglu I (August 2016). 2027:10.1152/ajprenal.00648.2010 1983:10.1016/j.jsbmb.2010.01.002 1939:10.1016/j.jsbmb.2008.06.013 865:The Journal of Cell Biology 202:Joseph A. Craig High School 2539: 2321:10.1016/j.gene.2016.04.053 1893:10.1016/j.gene.2015.12.061 1622:J Steroid Biochem Mol Biol 465: 192:Israel Hanukoglu attended 2483:21st-century Turkish Jews 2478:20th-century Turkish Jews 2438:21st-century Israeli Jews 2433:20th-century Israeli Jews 2262:10.1007/s00418-016-1535-3 2212:10.1007/s10735-018-9759-2 2169:10.1007/s00418-011-0904-1 1370:10.1080/03602530600570040 1245:10.1007/s00239-017-9821-9 261:Steroid hormone synthesis 130: 67: 2518:20th-century biochemists 2503:21st-century biochemists 1711:Human Molecular Genetics 1506:10.1073/pnas.90.22.10509 812:Hanukoglu I (Dec 1992). 489:Ofra Lax (11 May 2003). 352:and ENaC type channels. 237:Contributions to science 1358:Drug Metabolism Reviews 1105:10.1073/pnas.85.19.7104 194:tr:Şişli Terakki Lisesi 1834:Clinical Endocrinology 1809:10.1210/jcem.87.7.8674 1405:Biochim. Biophys. Acta 1331:10.1006/abbi.1995.1182 1292:10.1006/abbi.1993.1452 1202:10.1006/jmbi.1999.2807 877:10.1083/jcb.111.4.1373 374:American Field Service 245:Structures of keratins 228:. He then went to the 198:American Field Service 144: 1684:10.1210/jcem-73-5-936 1552:10.1530/eje.0.1330552 725:Biochem Mol Biol Educ 454:for establishing the 282:adrenodoxin reductase 251:University of Chicago 2448:Molecular biologists 1352:Hanukoglu I (2006). 2443:Israeli biochemists 2382:on 22 December 2016 1724:10.1093/hmg/5.2.293 1497:1993PNAS...9010509R 1237:2017JMolE..85..205H 1151:1990Natur.343...38S 1096:1988PNAS...85.7104S 324:Tel Aviv University 155:scientist. He is a 2357:2015-06-27 at the 2290:Israel Hanukoglu. 2123:10.1111/febs.13840 2075:10.1111/febs.12765 1761:10.1038/ng0396-248 528:Israel Hanukoglu. 441:Benjamin Netanyahu 2376:www.science.co.il 1090:(19): 7104–7108. 738:10.1002/bmb.20746 688:10.1038/nsmb.2330 415:Global rank: 22nd 216:College education 165:molecular biology 134: 133: 69:Scientific career 2530: 2391: 2390: 2388: 2387: 2378:. 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Index

Thesis
Doctoral advisor
Neal L. First
W.W. Cleland
Turkish
Turkish
Israeli
full professor
biochemistry
molecular biology
Ariel University
prime minister
Israel
tr:Şişli Terakki Lisesi
American Field Service
Joseph A. Craig High School
Janesville
Wisconsin
Hebrew University of Jerusalem
University of Wisconsin–Madison
University of Chicago
Elaine Fuchs
steroid hormones
P450scc
Technion-Israel Institute of Technology
adrenodoxin reductase
Rossmann fold
ACTH
Jerusalem
Aaron Hanukoglu

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