- ADJUNCT ASSOCIATE PROFESSOR Medicine, Endocrinology, Diabetes and Bone Disease
The GH-IGF axis is central to many biological processes in animals including growth, development, metabolism, reproduction, cardiovascular system, gastrointestinal system, renal system and longevity. In humans, several clinical diseases involving loss of components of either the GH pathway or the IGF pathway result in decreased growth, diabetes, obesity and increased cancer risk.
IGF-1 exerts both endocrine and autocrine/paracrine effects. IGF-1 is produced in the liver in response to pituitary GH, as well as in extra-hepatic tissues, where gene expression is regulated by tissue-specific factors in addition to GH. The circulating IGF-1 forms complexes with a family of high affinity IGF-binding proteins (IGFBPs) and an acid labile subunit (ALS) that protect IGF-1 from proteolytic degradation and regulate the ability of IGF-1 to activate receptors on the surface of its target cells.
The primary goal of this laboratory is to understand the molecular biological mechanisms of GH-IGF axis in the human disease process and also to facilitate the rational development of new and effective therapies. The main focus is the analysis of the developmental functions of the GH-IGF system by a genetic approach. We are adapting the new high-throughput recombineering system to make conditional knockout mice, which allows a gene to be inactivated in a tissue- or temporal-specific fashion. Gene knockout mice provide a powerful tool for elucidating gene function in the whole animals, which will shed insight into corresponding human diseases.
Wu Y, Sun H, Mejia W, Novosyadlyy R, Nunez N, Chen X, Mendoza A, Hong S, Khanna C, Brodt P, Yakar S. IGF-1 regulates the liver microenvironment in obese miceand promotes liver metastasis.. Cancer Research 2010 Jan; 1(70): 57-67.
Wu Y, Wang C, Sun H, LeRoith D, Yakar S. High-efficient FLPo deleter mice in C57BL/6J background.. PLoS One 2009; 4(11): e8054.
Wu Y, Sun H, Yakar S, LeRoith D. Elevated levels of insulin-like growth factor (IGF-1) in serum rescuse the severe growth retardation of IGF-1 null mice.. Endocrinology 2009 Sept; 150(9): 4395-4403.
Fritton JC, Emerton KB, Sun H, Kawashima Y, Mejia W, Wu Y, Rosen CJ, Panus D, Bouxsein M, Majeska RJ, Schaffler MB, Yakar S. Growth hormone protects against ovariectomy-induced bone loss in states of low circulating IGF-1.. J Bone Miner Res 2009 July; PMID(19619004).
Yakar S, Rosen C, Bouxsein M, Sun H, Wu Y, Gavrilova O, Gutierrez M, Hwang D, Pennisi P, Frystyk J, Boisclair Y, Ointar J, Hector J, Domene H, Cohen P, Clemmons D, LeRoith D. IGF-1 carrier components determine skeletal growth and metabolism by both direct and indirect mechanisms.. FASEB J 2009 March; 23(3): 709-719.
Toyoshima Y, Monson C, Duan C, Wu Y, Gao C, Yakar S, Sadler KC, LeRoith D. The role of insulin receptor signaling in zebrafish embryogenesis.. Endocrinology 2008; 149(12): 5996-6005.
Zhang J, Wu Y, Zhang Y, LeRoith D, Bernlohr DA, Chen X, . The role of lipocalin 2 in the regulation of inflammation in adipocytes and macrophages. Molecular endocrinology 2008; 22(6): 1416-1426.
Xiang CC, Wu Y, Ma L, Ding L, Lisinski I, Brownstein MJ, Cushman SW, Chen X. Characterisation of insulin-resistant phenotype of cultured rat primary adipose cells.. Diabetologia 2007; 50(5): 1070-1079.
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