Israel Hanukoglu - Contributions To Science

Contributions To Science

Hanukoglu was awarded the first Hans Lindner Prize (1988) of the Israel Endocrine Society, and Lubell Award (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. The importance of the motifs he identified was confirmed by re-engineering of coenzyme specificities of enzymes.

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. 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.

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. 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.

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

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 channels (ENaC). They were the first to identify that mutations in ENaC subunits result in the hereditary disease of pseudohypoaldosteronism type I. 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. 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.

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.

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