Alan Attie

Position title: Professor

Email: adattie@wisc.edu

Phone: 608-262-1372

Address:
Biochemistry
Genetics of type 2 diabetes and related metabolic diseases

Address
534 Biochemistry
Lab website
https://biochem.wisc.edu/faculty/attie
Education
Ph.D., University of California-San Diego, 1980, Postdoctoral Research: University of California-San Deigo, Department of Medicine
Department
Biochemistry
Research Interest
Genetics of metabolic disease, especially diabetes, genetics of response to diets.
Research Fields
Disease Biology, Cell Biology, Computational, Systems & Synthetic Biology, Gene Expression, Genomics & Proteomics, Human, mouse & rat

Research Description:
Genetics of Diabetes, beta-cell biology, lipid metabolism Our laboratory studies genetic and biochemical processes underlying metabolic diseases, especially obesity, diabetes, and hypercholesterolemia. The obesity and diabetes epidemics The obesity epidemic is evoking a parallel epidemic in metabolic diseases, including diabetes, cardiovascular disease, hypertension, fatty liver, neurological diseases, and kidney failure. Genetic factors contribute to these diseases and obesity acts as a stressor that elicits phenotypes that might otherwise be silent. Our laboratory uses mouse genetics to identify novel causal and responsive genes leading to metabolic diseases. Diabetes Diabetes results from an absolute or a relative insulin deficiency. Pancreatic β-cells sense blood glucose and respond by secreting insulin. Insulin lowers blood glucose by promoting its clearance from the circulation and by inhibiting gluconeogenesis. In type 2 diabetes, there is an increased requirement for insulin, caused by a dampened response to the hormone, coupled with a failure to meet this increased requirement. This bottleneck is strongly influenced by genes acting in β-cells. We study these genes to discover mechanisms by which β-cells sense glucose and trigger insulin secretion. Research Genetic Pipeline. Our projects come from genes we identify in our screens using mouse genetics. We then study these genes in transgenic mice and in cell lines. 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. One of those genes is the transcription factor NFATc2. We are studying its regulation in relation to β-cell function and diabetes. Genetics of metabolic flux. There is tremendous variability in the response of individuals to different diets. Likewise, mouse strains vary in their response to diet. These responses are due to differences in the control of metabolic pathways. We are conducting a genetic screen using stable isotope tracers to measure metabolic flux through many pathways in mice subjected to two extreme diets. We will map the genetic drivers responsible for strain differences in diet responsiveness.


Representative Publications:
Search PubMed for more publications by Alan Attie

Simonett SP, Shin S, Herring JA, Bacher R, Smith LA, Dong C, . . . Attie AD. Identification of direct transcriptional targets of NFATC2 that promote beta cell proliferation. J Clin Invest. 2021;131(21).

Attie AD, Schueler KM, Keller MP, Mitok KA, Simonett SP, Hudkins KL, . . . Alpers CE. Reversal of hypertriglyceridemia in diabetic BTBR ob/ob mice does not prevent nephropathy. Lab Invest. 2021;101(7):935-41.

Linke V, Overmyer KA, Miller IJ, Brademan DR, Hutchins PD, Trujillo EA, . . . Coon JJ. A large-scale genome-lipid association map guides lipid identification. Nat Metab. 2020;2(10):1149-62.

Kemis JH, Linke V, Barrett KL, Boehm FJ, Traeger LL, Keller MP, . . . Rey FE. Genetic determinants of gut microbiota composition and bile acid profiles in mice. PLoS Genet. 2019;15(8):e1008073.

Keller MP, Rabaglia ME, Schueler KL, Stapleton DS, Gatti DM, Vincent M, . . . Attie AD. Gene loci associated with insulin secretion in islets from non-diabetic mice. J Clin Invest. 2019;129(10):4419-32.

Keller MP, Gatti DM, Schueler KL, Rabaglia ME, Stapleton DS, Simecek P, . . . Attie AD. Genetic Drivers of Pancreatic Islet Function. Genetics. 2018;209(1):335-56.

Mitok KA, Freiberger EC, Schueler KL, Rabaglia ME, Stapleton DS, Kwiecien NW, . . . Attie AD. Islet proteomics reveals genetic variation in dopamine production resulting in altered insulin secretion. J Biol Chem. 2018;293(16):5860-77.