Dr. Lönnerdal’s research program integrates observations in human population with studies in animal and cell culture models to investigate two main areas of research: factors that impact pediatric nutrition and the regulation of trace element metabolism, particularly during the unique physiological conditions of pregnancy, lactation and infancy. Current interests of members of our laboratory include:

(1) Studies on factors affecting breast milk composition, including maternal nutrition, hormones and stage of lactation
Milk composition is not static and is often affected by diet. While maternal nutriture is often sub-optimal in both developed and developing countries, the contribution of inadequate maternal nutrition to the regulation of milk composition is not well defined. Studies are currently being conducted to determine the effects of single or multiple micronutrient deficiencies on hormonal secretion, mammary gland biology and milk composition.

(2) Mechanisms for nutrient uptake by mammary cells as well as expression of genes encoding human milk proteins
While many milk components are produced de novo by the mammary gland, there are a number of others that must be transported from material circulation. In addition to trace elements, vitamins such as vitamin A and B12 must be transferred into milk in order to insure adequate nutriture in the offspring. The identification of factors responsible for the transport of minerals and vitamins into the mammary gland as well as the regulation of these processes is currently being investigated.

(3) Bioactive factors in milk
Milk is a complex biological fluid which has been viewed primarily as a food that provides energy and essential nutrients for optimal health and development of young animals. However, it also contains a variety of bioactive components that include a mix of cells, bioactive proteins, hormones and other growth and immunological factors. A number of these factors are able to modulate the intestinal microflora, by enhancing host-friendly bacterial growth or inhibiting pathogenic bacteria, thus enhancing the health of the breastfed infant. The identification, purification and functional assessment of these bioactive factors is currently being investigated.

(4) Bioavailability of nutrients to infants and how this is affected by the mode of feeding
A number of nutrients, are better absorbed from breast milk than from infant formula, possibly as a result of complex interactions between nutrients and other factors found in breast milk. For example, breast milk contains lactoferrin, which is an iron binding protein facilitates the absorption of iron during infancy. We have identified lactoferrin receptor and successfully cloned the gene encoding this protein. Current studies are underway to determine the biological significance to lactoferrin receptor and define the cellular mechanisms through which it facilitates its activity. Additionally, a number of inhibitory factors exist in infant formula which necessitates the supplementation of nutrient levels to ensure adequate nutrient absorption by the infant. Using animal and cell culture models and in vitro techniques we are currently identifying these factors and their effect on nutrient absorption.

(5) Enhancement of iron, zinc, copper and selenium nutrition of infants, children and adolescents
Micronutrient deficiencies are common worldwide and children are a particularly vulnerable population. We have used various strategies have been used to combat these deficiencies including supplementation, food fortification and modification of food preparation and processing methods. A new possible strategy we are pursuing is to use biotechnology to improve trace element nutrition. Genetic engineering can be used in several ways; the most obvious is to increase the trace element content of staple foods such as cereals and legumes. This may be achieved by introduction of genes that code for trace element-binding proteins, over-expression of storage proteins already present and/or increased expression of proteins that are responsible for trace element uptake into plants. However, even very high levels of expression may not substantially increase the iron and zinc contents unless many atoms of trace elements are bound per protein molecule. Another possibility is to introduce a protein that specifically enhances trace element absorption even in the presence of naturally occurring inhibitors, thus improving bioavailability. Genetically modifying plants so that their contents of inhibitors of trace element absorption such as phytate are substantially reduced is another approach. Studies are currently underway to study effects of enhancing iron, zinc, copper and selenium nutrition through the use of traditional methods as well as the use of genetically modified foods in both human populations as well as through the use of animal and cell culture models.

(6) The regulation of trace element uptake and transport across biological membranes, specifically by the placenta, intestine, liver and mammary gland
Recently, a number mammalian proteins have been described which participate in Zn, Cu or Fe trafficking across membranes. We are currently investigating the regulation of mineral transport in animal and cell culture models specifically in the placenta, intestine, liver and mammary gland from the transcriptional to the post-translational level. These studies use a variety of molecular and cellular techniques such as quantitative reverse transcription PCR and Northern blots, gene cloning, gene over-expression and silence, pulse-chase labeling, Western blots, immunohistochemistry and immunofluorescence.

(7) Nutrient-nutrient interactions
There is increasing evidence that micronutrient deficiencies do not exist independently and often a deficiency in one micronutrient creates a secondary deficiency in another. We are currently conducting studies to determine the interaction between deficiencies in a number of micronutrients such as Fe, Zn, Cu and vitamin A.