The mission of the La Merrill Lab is to understand susceptibility to environmental diseases. We consider susceptibilities to disease that may result from environmental insults during the exquisitely sensitive developmental period, from poor diet and ensuing metabolic diseases, and from genetic and epigenetic predispositions.
Much of our susceptibility research is centered on the developmental basis of environmental disease. We conduct research on how developmental exposure to persistent organic pollutants increases risk of metabolic disorders in adults. The possibility that the nutritional environment during development may increase risk of adult disease has established the 'developmental basis of adult health and disease' hypothesis. We are exploring the relatively under-explored possibility that increased risk of metabolic disorders is due to dietary exposure to toxicants, such as pesticides and bioaccumulative compounds.
The La Merrill lab examines how prenatal toxicant exposures increase susceptibility to obesity, type 2 diabetes, dyslipidemia, and hypertension (together known as “metabolic syndrome”) during adulthood. Metabolic syndrome increases risk of cardiovascular disease and breast cancer, two major causes of death worldwide, hence we also investigate how prenatal toxicant exposures increase risk of cardiovascular disease and breast cancer. We have found that perinatal exposure to chemicals can cause metabolic changes in adults which increase risk for diseases such as type 2 diabetes, obesity, hypertension, breast cancer, and cardiovascular disease.
The La Merrill lab is also interested in how obesity resulting from high fat diet increases susceptibility to these diseases. We have recapitulated known associations between obesity and risk of type 2 diabetes and breast cancer in our mouse models. Interestingly, we have found that the risk of these diseases due to toxicant exposure and obesity is greater than you would expect from the singular effects of either obesity or toxicants on disease risk. We continue to explore why obese individuals are especially susceptible to toxicants and to diseases.
The La Merrill lab also evaluates genetic susceptibility to environmental disease. Our research on gene x environment interactions has been primarily focused on the dietary fat environment. We have used genomic approaches in mouse populations to reveal that the majority of genetic modifiers of mammary cancer significantly interacted with high fat diet. We plan to expand our research of genetic susceptibility using the Collaborative Cross, an emerging population of inbred mice strains with fine mapped SNPs designed to model the heterogeneous human population for the delineation of genetic and environmental determinants of disease.
In order to address our research questions, the La Merrill Lab conducts both epidemiological- and experimental- research to integrate human observations with mechanistic investigations. We believe this research approach will ultimately lead to improved disease prevention through primary prevention of exposure and secondarily through lifestyle- and pharmaceutical- interventions.