grow magazine article, Spring 2015, about Attie’s Diabetes research click here
Genetics of Metabolic Disease
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.
Genetics delivers causal pathways to disease
We apply a broad definition of phenotype to our genetic screens. This includes physiological measurements and various -omics-derived molecular traits; transcriptomics, proteomics, metabolomics, lipidomics, and assessment of microbiota. We genetically map all of these types of phenotypes to develop causal networks and actionable genes associated with metabolic disease.
Genes that regulate insulin secretion. Our genetic screens have delivered candidate genes that affect insulin secretion. These include transcription factors, enzymes, and proteins that affect vesicle trafficking.
How non-coding DNA contributes to disease susceptibility. The great majority of DNA variants that contribute to disease are in non-coding regions of DNA. They often act by changing chromatin structure and by altering expression of protein-coding genes. A major challenge is discovering what genes are affected by these DNA variants. We integrate human and mouse genetics to identify DNA segments that we study using CRSPR/Cas technology in vivo.
Lipid metabolism. By combining mass spec-based lipidomics with genetics, we have identified candidate genes that regulate the abundance of many lipids. Some of these lipids act in a hormone-like fashion to regulate metabolism.
The role of amylin in diabetes. Amylin (aka islet amyloid polypeptide precursor) is a small peptide hormone that is co-secreted with insulin. It can form toxic multimers and lead to diabetes. Martin Zanni (Dept of Chemistry) has developed mutant forms of amylin that form stable toxic multimers. We are looking for a new graduate student or post-doc to discover how these molecules are toxic to b-cells.
We are looking for talented post-doctoral and pre-doctoral scholars interested in multi-disciplinary projects centered around metabolic disease. Our projects encompass mouse and human genetics, bioinformatics, mammalian physiology, cell biology, transcriptomics, lipidomics, and proteomics.
Our lab is affiliated with the following programs:
- Integrated Program in Biochemistry
- Cellular and Molecular Biology Training Program
- Nutritional Sciences Training Program
- Genetics Training Program
- Cell and Molecular Pathology Training Program
Alan D. Attie, Ph.D.