Alan D. Attie, PhD

Professor
Biochemistry
Address: 
543a Biochemistry Addition
433 Babcock Dr
Madison, WI 53706
Telephone: 
(608) 262-1372
Focus Groups: 
Signal Transduction
Education: 
PhD, University of California-San Diego
Research Summary: 
Genetics of type 2 diabetes and lipid metabolism
Research Detail: 

Genetics of type 2 diabetes and lipid metabolism

Our laboratory studies genetic and biochemical processes underlying metabolic diseases, especially obesity and diabetes, and disorders in cholesterol and lipoprotein metabolism.

Genetic pipeline.

We use mouse genetics to discover new genes and pathways that lead to metabolic disease. Our main focus has been obesity-induced type 2 diabetes. Obesity increases the demand for insulin (insulin resistance), thus placing a demand on pancreatic b-cells to secrete more insulin. The capacity of b-cells to meet this demand is largely affected by genetic variation. We have identified several genes that affect b-cell replication and insulin secretion.

Newly discovered genes.

We recently completed a screen for genes that affect insulin secretion. We identified 30 genetic regions harboring causal genes. We selected three regions and generated knockout mouse models that validate these genes. The genes encode a protein kinase, a protein phosphatase, and a transcription factor. These genes are the gateway into novel pathways that regulate insulin secretion.

Gene causal networks and diabetes.

By combining global gene expression profiling and genetics, we are able to construct causal networks linking specific genes with diabetes phenotypes. We are applying our genetic and bioinformatic data to identify key drivers of gene expression

Selected Publications: 
Genetic Drivers of Pancreatic Islet Function. Keller MP, Gatti DM, Schueler KL, Rabaglia ME, Stapleton DS, Simecek P, Vincent M, Allen S, Broman AT, Bacher R, Kendziorski C, Broman KW, Yandell BS, Churchill GA, Attie AD. Genetics. 2018 May;209(1):335-356. doi: 10.1534/genetics.118.300864. Epub 2018 Mar 22. PMID: 29567659
Islet proteomics reveals genetic variation in dopamine production resulting in altered insulin secretion. Mitok KA, Freiberger EC, Schueler KL, Rabaglia ME, Stapleton DS, Kwiecien NW, Malec PA, Hebert AS, Broman AT, Kennedy RT, Keller MP, Coon JJ, Attie AD. J Biol Chem. 2018 Apr 20;293(16):5860-5877. doi: 10.1074/jbc.RA117.001102. Epub 2018 Mar 1. PMID: 29496998
Intracellular lipid metabolism impairs β cell compensation during diet-induced obesity. Ye R, Gordillo R, Shao M, Onodera T, Chen Z, Chen S, Lin X, SoRelle JA, Li X, Tang M, Keller MP, Kuliawat R, Attie AD, Gupta RK, Holland WL, Beutler B, Herz J, Scherer PE. J Clin Invest. 2018 Mar 1;128(3):1178-1189. doi: 10.1172/JCI97702. Epub 2018 Feb 19. PMID: 29457786
Perilipin 5 and liver fatty acid binding protein function to restore quiescence in mouse hepatic stellate cells. Lin J, Zheng S, Attie AD, Keller MP, Bernlohr DA, Blaner WS, Newberry EP, Davidson NO, Chen A.J Lipid Res. 2018 Mar;59(3):416-428. doi: 10.1194/jlr.M077487. Epub 2018 Jan 9. PMID: 29317465
Targeted Mass Spectrometry Approach Enabled Discovery of O-Glycosylated Insulin and Related Signaling Peptides in Mouse and Human Pancreatic Islets. Yu Q, Canales A, Glover MS, Das R, Shi X, Liu Y, Keller MP, Attie AD, Li L. Anal Chem. 2017 Sep 5;89(17):9184-9191. doi: 10.1021/acs.analchem.7b01926. Epub 2017 Aug 7.
BAIAP3, a C2 domain-containing Munc13 protein, controls the fate of dense-core vesicles in neuroendocrine cells. Zhang X, Jiang S, Mitok KA, Li L, Attie AD, Martin TFJ. J Cell Biol. 2017 Jul 3;216(7):2151-2166. doi: 10.1083/jcb.201702099. Epub 2017 Jun 16. PMID: 28626000
Statistical Methods for Latent Class Quantitative Trait Loci Mapping. Ye S, Bacher R, Keller MP, Attie AD, Kendziorski C. Genetics. 2017 Jul;206(3):1309-1317. doi: 10.1534/genetics.117.203885. Epub 2017 May 26. PMID: 28550015
Host Genotype and Gut Microbiome Modulate Insulin Secretion and Diet-Induced Metabolic Phenotypes. Kreznar JH, Keller MP, Traeger LL, Rabaglia ME, Schueler KL, Stapleton DS, Zhao W, Vivas EI, Yandell BS, Broman AT, Hagenbuch B, Attie AD, Rey FE. Cell Rep. 2017 Feb 14;18(7):1739-1750. doi: 10.1016/j.celrep.2017.01.062. PMID: 28199845
How mice are indispensable for understanding obesity and diabetes genetics. Attie AD, Churchill GA, Nadeau JH. Curr Opin Endocrinol Diabetes Obes. 2017 Apr;24(2):83-91. doi: 10.1097/MED.0000000000000321. Review. PMID: 28107248
The Transcription Factor Nfatc2 Regulates β-Cell Proliferation and Genes Associated with Type 2 Diabetes in Mouse and Human Islets. Keller MP, Paul PK, Rabaglia ME, Stapleton DS, Schueler KL, Broman AT, Ye SI, Leng N, Brandon CJ, Neto EC, Plaisier CL, Simonett SP, Kebede MA, Sheynkman GM, Klein MA, Baliga NS, Smith LM, Broman KW, Yandell BS, Kendziorski C, Attie AD. PLoS Genet. 2016 Dec 9;12(12):e1006466. doi: 10.1371/journal.pgen.1006466. eCollection 2016 Dec. PMID: 27935966