Alan D. Attie

Genetics of diabetes, beta-cell biology, lipid metabolism, and diet outcome

Genetics, Metabolism, and the Biology of Diabetes

Our laboratory seeks to answer one of the most important questions in modern medicine:
Why do some individuals develop diabetes and metabolic disease while others remain healthy, even under the same environmental challenges?
We investigate the genetic and molecular mechanisms that control insulin secretion, glucose homeostasis, lipid metabolism, and susceptibility to metabolic disease. Our work combines mouse genetics, systems biology, metabolomics, molecular biology, and physiology to discover new pathways that regulate metabolism and to understand how their dysfunction leads to diabetes, obesity, fatty liver disease, and cardiovascular disease.

Understanding the β-Cell

The pancreatic β-cell is responsible for sensing blood glucose and secreting insulin with remarkable precision. Failure of this process is a central cause of type 2 diabetes.
Our laboratory studies the genes and pathways that allow β-cells to sense nutrients, generate metabolic signals, and release insulin. Using genetic models and state-of-the-art physiological approaches, we identify novel regulators of β-cell function and determine how genetic variation influences diabetes risk.

Discovering New Metabolic Pathways Through Genetics

Many of our projects begin with a simple question:
Which genes make one individual metabolically healthy and another susceptible to disease?
To answer this question, we use genetically diverse mouse populations that model the genetic complexity of human populations. These approaches allow us to identify previously unknown genes that influence insulin secretion, obesity, lipid metabolism, and metabolic resilience.
Once a candidate gene is discovered, we pursue its mechanism using molecular, cellular, and physiological approaches. This “gene-to-mechanism” pipeline provides trainees with experience spanning discovery science through functional validation.

Systems Genetics and Metabolic Networks

Metabolic diseases arise from interactions among thousands of genes, proteins, and metabolites. We combine genetics with transcriptomics and metabolomics to build causal networks that reveal how these components interact to control metabolic health.

Current projects use stable-isotope tracing and large-scale metabolomic profiling to map genetic regulators of metabolic pathways and to understand why individuals differ dramatically in their responses to diet.