The Lawson Lab addresses important questions about the genotype – phenotype relationship that must be answered to understand variation in metabolic traits. Specifically:

  • Are particular metabolic traits more genetically or epigenetically controlled?
  • How does diet affect the relative contribution of genetics or epigenetics?
  • Do differences in genetic and epigenetic modes of regulation result in discordance among metabolic traits?

Answers to these questions are critical to understanding why some individuals with metabolic complications respond to lifestyle modifications while others require therapeutic interventions. Further, understanding how diet modifies genetic and epigenetic effects might shed light on why some obese individuals develop metabolic complications while others remain metabolically normal.

We have found that the modes (genetic or epigenetic) of regulating genes underlying variation in metabolic traits vary depending on environment rather than being universal. We aim to characterize the genotype-phenotype relationship using a model system, and then translate our results to human studies. The ability to predict such effects would be a step towards precision medicine and towards understanding how associations among metabolic traits evolved.


Parent-of-Origin Effects

Parent-of-origin effects occur when the phenotypic effects of an allele depends on whether it is inherited from the mother or the father. We have found prevalent complex parent-of-origin effects on dietary obesity-related metabolic traits. One of our main research goals is to understand the molecular mechanisms that generate these complex phenotypic patterns. 




Unraveling Metabolically Heathy Obesity

While studying the interaction of high fat diet and genetic background on mouse metabolism, we identified an unexpected effect of aging in a strain of mice that develop normoglycemic obesity as they age.



High fat-fed mice almost always have higher basal glucose than low fat-fed mice, but our high fat-fed mice develop lower basal glucose comparable to low fat-fed mice at 30-weeks. Concurrently, these mice develop a dramatic expansion of their interscapular brown adipose tissue (hump) between the ages of 20- and 30-weeks. We are actively researching both of these phenomena to understand their relationship with each other and the causes and consequences of each phenotype. Understanding the molecular and physiological mechanisms that underlie this healthy obesity in our mice will provide critical information that could open the door for innovative therapies for metabolic dysfunction in obesity.


 Improving ß-cell Function

Improving β-cell function is a major therapeutic goal in diabetes research. Our mice provide a unique model for studying the relationship between brown adipose tissue and the natural enhancement of insulin production.



Our high fat-fed mice: (A) improve glycemic control between 20- and 30-weeks; (B) increase circulating insulin levels between 20- and 30-weeks; and (C) have dramatically larger pancreatic islets than low-fat controls at 30-weeks of age. Our mice provide a unique model for studying ß-cell expansion and enhancement of insulin production. Understanding the changes that occur during this transition can provide insight into how islets are regulated, and may shed light on important metabolic pathways with therapeutic potential.