Research

RESEARCH OVERVIEW

Research in the Kelleher Lab is broadly aimed at understanding the role of diet, genetics, and environmental contaminants on the role and regulation of zinc transport in mammary and intestinal epithelial cells. We utilize cultured cells and transgenic mouse models, to understand the cellular mechanisms that integrate nutrition with genetics, cell biology, and physiology. 

A long-term focus of our research has been to understand the molecular role of the zinc transporter ZnT2 (SLC30A2) in regulating mammary gland function during lactation and involution and dysregulation in breast cancer. These studies have been expanded to focus on understanding the role and regulation of ZnT2 in select intestinal cells, and the role zinc and ZnT2 play in mucosal inflammation and  the risk for intestinal disease.

In addition, current studies aim to understand how diet, genetics and environmental contaminants affect breast cell function, milk production  and composition more broadly, and how these factors underlie low milk supply and poor breastfeeding outcomes.

Role of zinc & ZnT2 in intestinal function
The intestine acts as a barrier to prevent the passage of harmful intraluminal entities including foreign antigens, microorganisms and their toxins, and second, it is responsible for regulating the absorption of nutrients. Factors such as diet, genetics, and environmental exposures have important implications on intestinal function, and can affect the risk for intestinal illness such as inflammatory bowel disease (IBD) and necrotizing enterocolitis (NEC). A critical gap in knowledge is our lack of understanding regarding how dietary factors, genetics, and environmental contaminants affect intestinal function and risk for disease.

Fundamental questions our research works to address is (1) What is the role of zinc  in intestinal function? (2) How does zinc dysregulation affect the gut microbiome, mucosal inflammation, and risk for intestinal disorders?

Nutrigenetics and mammary gland function
Mammary glands are highly specialized exocrine glands unique to mammals that have developed to produce milk to nourish the developing offspring. Human milk is a complex biological fluid that provides nutrients and non-nutritive factors for optimal growth and development. The benefits of breastfeeding on infant health are indisputable and include optimized growth, neurological development and immune function. These benefits extend throughout adulthood to include reduced risk of obesity and metabolic syndrome. Factors such as diet, genetics, and environmental exposures have important effects on mammary cell function, and can affect the ability to produce enough high-quality milk to nourish the infant. A critical gap in knowledge is our lack of understanding regarding factors that affect mammary gland function, the production and secretion of milk, and risk for low milk supply.

Fundamental questions our research works to address are (1) How do maternal exposures affect mammary gland function? (2) Why are so many women unable to to produce enough high-quality milk? (3) Can we develop novel therapeutic strategies to improve milk production in breastfeeding women?