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ZFIN ID: ZDB-LAB-160822-1
Schlegel Lab
PI/Director: Schlegel, Amnon
Contact Person: Hugo, Sarah
Address: Eccles Institute of Human Genetics, Building 533, Room 3240B 15 North 2030 East Salt Lake City, Utah 84112, USA
Country: United States
Phone: (801) 585-0733
Fax: (801) 585-0701
Line Designation: z

Show all 9 genomic features

My laboratory takes a multi-pronged approach to identifying and characterizing novel genes involved in lipid and glucose metabolism. Starting with unbiased, forward genetic screens in zebrafish, we isolate mutants with lipid phenotypes of interested (e.g., inappropriate accumulation of lipids in the liver, altered adipose lipid mass). We then clone and characterize the affected genes. We also use modern genetic methods to delete or selectively express genes of therapeutic interest, with a particular emphasis on the control of intestinal lipid handling as a platform for treating dyslipidemia and atherosclerosis. We take similar approaches to elucidating the roles of gene identified in human population genetics studies in glucose metabolism and type 2 diabetes mellitus pathogenesis. Characterization of mutant and transgenic zebrafish involves a broad range of methods spanning sophisticated microscopy (confocal and transmission electron), biochemical techniques, and, where appropriate, pilot pharmacological studies. We use in vitro enzymology, cell culture (including primary culture of human hepatocytes), and rodent (mice and rats) physiology to complement our work in zebrafish.

Benítez-Santan, Tibiabin Post-Doc Karanth, Santhosh Post-Doc Hugo, Sarah Technical Staff

Karanth, S., Chaurasia, B., Bowman, F.M., Tippetts, T.S., Holland, W.L., Summers, S.A., Schlegel, A. (2019) FOXN3 controls liver glucose metabolism by regulating gluconeogenic substrate selection. Physiological Reports. 7:e14238
Erickson, M.L., Karanth, S., Ravussin, E., Schlegel, A. (2019) FOXN3 hyperglycemic risk allele and insulin sensitivity in humans. BMJ open diabetes research & care. 7:e000688
Ahorukomeye, P., Disotuar, M.M., Gajewiak, J., Karanth, S., Watkins, M., Robinson, S.D., Flórez Salcedo, P., Smith, N.A., Smith, B.J., Schlegel, A., Forbes, B.E., Olivera, B., Hung-Chieh Chou, D., Safavi-Hemami, H. (2019) Fish-hunting cone snail venoms are a rich source of minimized ligands of the vertebrate insulin receptor. eLIFE. 8
Karanth, S., Schlegel, A. (2019) The Monocarboxylate Transporter SLC16A6 Regulates Adult Length in Zebrafish and Is Associated With Height in Humans. Frontiers in Physiology. 9:1936
Karanth, S., Adams, J.D., Serrano, M.L.A., Quittner-Strom, E.B., Simcox, J., Villanueva, C.J., Ozcan, L., Holland, W.L., Yost, H.J., Vella, A., Schlegel, A. (2018) A Hepatocyte FOXN3-α Cell Glucagon Axis Regulates Fasting Glucose. Cell Reports. 24:312-319
Hugo, S.E., Schlegel, A. (2017) A genetic model to study increased hexosamine biosynthetic flux. Endocrinology. 158(8):2420-2426
Hugo, S.E., Schlegel, A. (2017) A genetic screen for zebrafish mutants with hepatic steatosis identifies a locus required for larval growth. Journal of anatomy. 230(3):407-413
Schlegel, A. (2016) Zebrafish Models for Dyslipidemia and Atherosclerosis Research. Frontiers in endocrinology. 7:159
Karanth, S., Zinkhan, E.K., Hill, J.T., Yost, H.J., Schlegel, A. (2016) FOXN3 Regulates Hepatic Glucose Utilization. Cell Reports. 15(12):2745-55
Schlegel, A., Gut, P. (2015) Metabolic insights from zebrafish genetics, physiology, and chemical biology. Cellular and molecular life sciences : CMLS. 72(12):2249-60
Safavi-Hemami, H., Gajewiak, J., Karanth, S., Robinson, S.D., Ueberheide, B., Douglass, A.D., Schlegel, A., Imperial, J.S., Watkins, M., Bandyopadhyay, P.K., Yandell, M., Li, Q., Purcell, A.W., Norton, R.S., Ellgaard, L., Olivera, B.M. (2015) Specialized insulin is used for chemical warfare by fish-hunting cone snails.. Proceedings of the National Academy of Sciences of the United States of America. 112(6):1743-1748
Schlegel, A. (2015) Studying lipoprotein trafficking in zebrafish, the case of chylomicron retention disease. Journal of molecular medicine (Berlin, Germany). 93(2):115-8
Cruz-Garcia, L., Schlegel, A. (2014) Lxr-driven enterocyte lipid droplet formation delays transport of ingested lipids. Journal of Lipid Research. 55(9):1944-58
Karanth, S., Tran, V.M., Kuberan, B., and Schlegel, A. (2013) Polyunsaturated fatty acyl-coenzyme As are inhibitors of cholesterol biosynthesis in zebrafish and mice. Disease models & mechanisms. 6(6):1365-77
Schlegel, A. (2012) Studying non-alcoholic fatty liver disease with zebrafish: a confluence of optics, genetics, and physiology. Cellular and molecular life sciences : CMLS. 69(23):3953-61
Hugo, S.E., Cruz-Garcia, L., Karanth, S., Anderson, R.M., Stainier, D.Y., and Schlegel, A. (2012) A monocarboxylate transporter required for hepatocyte secretion of ketone bodies during fasting. Genes & Development. 26(3):282-93
Karanth, S., Denovan-Wright, E.M., Thisse, C., Thisse, B., and Wright, J.M. (2009) Tandem duplication of the fabp1b gene and subsequent divergence of the tissue-specific distribution of fabp1b.1 and fabp1b.2 transcripts in zebrafish (Danio rerio). Genome. 52(12):985-992
Anderson, R.M., Bosch, J.A., Goll, M.G., Hesselson, D., Dong, P.D., Shin, D., Chi, N.C., Shin, C.H., Schlegel, A., Halpern, M., and Stainier, D.Y. (2009) Loss of Dnmt1 catalytic activity reveals multiple roles for DNA methylation during pancreas development and regeneration. Developmental Biology. 334(1):213-223
Karanth, S., Lall, S.P., Denovan-Wright, E.M., and Wright, J.M. (2009) Differential transcriptional modulation of duplicated fatty acid-binding protein genes by dietary fatty acids in zebrafish (Danio rerio): evidence for subfunctionalization and neofunctionalization of duplicated genes. BMC Evolutionary Biology. 9:219
Karanth, S., Denovan-Wright, E.M., Thisse, C., Thisse, B., and Wright, J.M. (2008) The evolutionary relationship between the duplicated copies of the zebrafish fabp11 gene and the tetrapod FABP4, FABP5, FABP8 and FABP9 genes. The FEBS journal. 275(12):3031-3040
Schlegel, A., and Stainier, D.Y. (2007) Lessons from "Lower" Organisms: What Worms, Flies, and Zebrafish Can Teach Us about Human Energy Metabolism. PLoS Genetics. 3(11):e199
Schlegel, A., and Stainier, D.Y. (2006) Microsomal Triglyceride Transfer Protein Is Required for Yolk Lipid Utilization and Absorption of Dietary Lipids in Zebrafish Larvae. Biochemistry. 45(51):15179-15187