Faculty Research Summaries

Steven A. Abrams, M.D.

Dr. Abrams' research projects are designed to use stable isotopes to evaluate mineral metabolism in infants and children. True dietary calcium absorption and bone formation and turnover are determined using orally and intravenously administered stable isotopes of calcium. Studies in children with mineral deficiencies are designed to determine the etiology of the mineral deficiency and the possible response to therapy. Studies are under way to evaluate the absorption of calcium and iron from milk, formula and dietary supplements in children age 4-12 months. Studies are being conducted to determine the iron needs of children with rheumatoid arthritis.

Janice Baranowski, M.P.H., R.D., L.D.
Ms. Baranowski's recent research has focused on improving fruit and vegetable consumption among children in a variety of settings (school, Boy Scout troops). She is currently developing and testing a computer-based food recording system and an interactive, multimedia, fruit and vegetable dietary behavior change program with elementary school children.  A newly funded grant will involve translating these successful methods into obesity prevention among children.

Tom Baranowski, Ph.D.
Dr. Baranowski is interested in three general topics:  why children eat the foods that they do; the design, implementation, and evaluation of dietary and physical activity change programs; and whether children's diet and physical activity practices become adult practices (behavior tracking). Most of his research in the last 10 years has focused on children's fruit, juice and vegetable intake. Recent projects also focus on the prevention of childhood obesity. The interventions have been school-based and with Boy Scouts. Intervention modalities  include classroom curriculum, interactive multimedia games, the internet and video tapes. The intended outcome of this work is the design of new public health programs effecting positive changes in the dietary habits and physical activities of children.

Dennis M. Bier, M.D.
Dr. Bier's primary research interest is the regulation of interorgan transport of metabolic fuels; specifically,  substrate and hormonal regulation of glucose, lipid, and protein/amino acid fuels. This work has taken two principal directions. The first entails the regulation of endogenous fuel availability for metabolic functions when a subject is ill and incapable of ingesting sufficient food. The second involves the assessment of the metabolic fates of ingested, exogenous fuels under various classical nutritional circumstances. In each instance, he has developed and employed a wide variety of stable isotope tracer kinetic methods to quantify substrate flux, metabolism, precursor-product relationships, and irreversible oxidation to excreted end products. The physiological information obtained also has been used to further assess aberrations in interorgan fuel transport consequent to a variety of pathological conditions.

Douglas G. Burrin, Ph.D.
The research objectives in Dr. Burrin's laboratory are to elucidate the cellular and hormonal signals that mediate the stimulatory effects of enteral nutrition on the growth and function of the neonatal intestine. Current studies are focused on the establishing the optimum quantity and composition of enteral nutrients necessary to maintain normal intestinal growth and function.  He has found that the secretion of gut-derived peptides, including glucagon-like peptide 2 (GLP-2), are closely correlated with enteral nutrient intake and produce trophic effects when given to neonatal pigs. Future studies will investigate the physiological significance of GLP-2 and how it impacts intestinal protein and amino acid metabolism in a neonatal pig model.

Nancy F. Butte, Ph.D.
The energy requirements of reproductive women and their infants are the focus of Dr. Butte's research. Her major interests are the functional consequences of variations in energy balance on pregnancy outcome, lactation performance, and infant growth and development. To further these evaluations, methodologies have been developed to measure energy expenditure and body composition in the populations of interest, including room respiration calorimeters and the doubly labeled water method for the measurement of free-living energy expenditure. Factors which predispose women to postpartum weight retention and later development of obesity are under investigation. Also, genetic and environmental factors that predispose infants and children to the development of obesity are being explored.

David M. Cohen, Ph.D.
Dr. Cohen's research concerns the regulated coordination of metabolic fluxes that is fundamental to health and sustained by adequate nutrition.  Study of the quantitative relationships among metabolic flux rates depends on accurate measurement of those rates, preferably in vivo.  To this end, he has investigated mathematical aspects of modeling rates of metabolic pathways, subsequent to the administration of isotopically labeled precursors.  An important focus of Dr. Cohen's work is the measurement of cerebral metabolism in vivo, using nuclear magnetic resonance spectroscopy.  Currently, he is developing a new method for estimation of the rate of cerebral glucose metabolism, with a substantial improvement in time resolution. In the long term, he hopes to learn more about the role of diet in support of brain metabolism and function.

Karen W. Cullen, Dr. P.H., R.D., L.D.
Dr. Cullen's research focuses on improving fruit and vegetable consumption and decreasing fat consumption among children and adolescents.  She has received funding to investigate social and environmental influences on children's diets, children's goal-setting processes for dietary behavior change, and the effect of school a la carte/snack bars on the fruit, vegetable, and fat intakes of middle school children. The results of these studies will be used to develop methods to assist children with goal-setting procedures as part of dietary behavior change programs; develop interventions to increase children's fruit and vegetable consumption, both at school and home; and document tracking of dietary behaviors among children.

Teresa A. Davis, Ph.D.
The goal of Dr. Davis' work is to determine the mechanisms by which nutrients, hormones, and growth factors regulate the high rate of muscle in the neonate.  To achieve this objective, her research focuses on four main areas: 1) the developmental changes in the regulation of protein synthesis and degradation by insulin, 2) the direct effect of amino acids on protein synthesis and their influence on insulin-stimulated protein synthesis, 3) the interaction of insulin and insulin-like growth factor-I in regulating protein turnover, and 4) the role of insulin and insulin-like growth factor-I in the anabolic response to growth hormone. To examine the effects of these endocrine and metabolic factors on tissue and whole body protein synthesis and degradation, stable isotopes and radioisotopes of amino acids are used during in vivo infusion studies in growing pigs. Novel techniques are being used which allow the active control of many of the hormones and substrates which interact to regulate protein anabolism.  Identification of the signal transduction proteins and translation initiation factors which regulate the high growth rate of muscle is a primary goal of her current research.      

Kenneth J. Ellis, Ph.D.
The goal of Dr. Ellis' research is to establish reference standards for body elemental composition in infancy, childhood and adolescence. This research focuses on the development and application of nuclearbased techniques for in vivo studies of human body composition. This approach provides knowledge of changes in growth and body composition that reflect the body's cumulative response to basic physiologic and metabolic processes. Detection of these changes often requires unique instrumentation  like the CNRC's whole body counters, which monitor ⁴⁰K, a naturally occurring isotope in the human. Dr Ellis has developed in vivo neutron activation techniques for clinical research and postmortem examinations, and he has extended the use of dual-energy X-ray absorptiometry to the examination of infants and children.

Marta Fiorotto, Ph.D.
The effects of chronic alterations in nutrient intake on the growth and development of skeletal muscle are the focus of Dr. Fiorotto's research.  Currently, she is attempting to show that the nature of skeletal muscle response is dependent on the developmental stage at which the organism is subjected to a nutritional insult. She is also attempting to identify the underlying factors responsible for the agerelated change in the sensitivity of skeletal muscle to nutritional perturbations. Dr. Fiorotto also will evaluate the consequences of changes in sensitivity on the numerous functional roles of skeletal muscle in the body.

Michael A. Grusak, Ph.D.
Dr. Grusak's laboratory is involved in both plant physiology and human nutrition research. His plant physiology research is focused on the mechanisms and regulation of nutrients in plants. His long-term goals are to characterize the dynamics of nutrient flow within plants to determine the biophysical/molecular signals which regulate source-to-sink nutrient partitioning, and ultimately to use this information to enhance the nutritional quality of plant foods. With regard to human nutrition research, his laboratory group has developed hydroponic growth facilities and protocols to label plant foods intrinsically with stable isotopes of important nutrients; these then are used to assess nutrient bioavailability and metabolism in humans.

Darryl L. Hadsell, Ph.D.
Current evidence supports the idea that insulin-gene family members are necessary for all aspects of mammary gland development and lactation.  Despite this, the mechanisms by which these peptides regulate mammary gland function are poorly understood. Research within Dr. Hadsell's laboratory focuses on three main goals. The first is to understand the specific mechanisms through which the receptors for insulin (IR) or IGF-I (IGF-IR) influence mammary gland development and/or lactation. The second is to understand the mechanisms through which nutrient availability influences mammary gland development and/or lactation.  The last is to understand how these factors interact at the transcriptional level to allow normal mammary gland development and lactation. The combined use of transgenic and knockout mice, tissue grafting strategies, and in-vitro cell culture models to modify IR or IGF-IR activity has provided insights into the mechanism through which apoptosis is regulated within the mammary gland.  These strategies have also led to a focus on putative insulin-responsive transcription factors as a means to define insulin-dependent milk protein gene expression

Peter M. Haney, M.D., Ph.D.
Dr. Haney's long-term research goal is to understand the molecular cell biology of lactation. Human milk is recognized as the ideal source of nutrition for infants, but the mechanisms and regulation of milk secretion are poorly understood at the cellular and molecular level. Current work is focused on glucose transport in the lactating mammary gland. Dr. Haney is studying the regulation of the amount, activity, and subcellular targeting of GLUT1, the only glucose transporter isoform identified in the mammary gland, in established and primary mammary epithelial cell lines, as well as in humans and rodents. Efforts are under way to elucidate the mechanisms of altered glucose transporter targeting, including Golgi sequestration and polarization of plasma membrane distribution, that he has observed during lactation. He will examine how GLUT1 gene expression and subcellular targeting regulate the synthesis of lactose. Dr. Haney has observed a novel protein, structurally similar to GLUT1, that resides in the Golgi, and is expressed only during lactation. He is pursuing the purification of this protein, the cloning of its cDNA, and the characterization of its possible role in regulating the targeting of GLUT1.

Morey W. Haymond, M.D.
The focus of Dr. Haymond's research program is to delineate and ultimately manipulate the hormone and substrate factors that regulate the absorption, assimilation, mobilization and disposal of carbohydrates in infants and children. The delicate balance of nutrient availability to meet the energy and growth needs of children is frequently disturbed as a result of chronic disease, infection, trauma and/or organ failure. In addition, the incidence of both type I and type II diabetes is on the rise, providing unique opportunities to study the effects of insulin, insulin resistance and obesity on macronutrient assimilation in children. These issues are being addressed in infants, children, adults, and when necessary, in animals, using a variety of stable isotope tracer techniques to estimate insulin sensitivity, absorption of carbohydrates, proteolysis, protein synthesis, gluconeogenesis, carbohydrate disposal, and substrate oxidation. Dr. Haymond is currently studying the impact of diet composition (fat and carbohydrate) on glucose homeostasis and macronutrient assertion; the impact of lactation production on glucose homeostasis in women; the precursors for lactose production and the factor(s) that regulate it; and the regulation of galactose and fructose metabolism by the liver.

William C. Heird, M.D.
Dr. Heird's research concerns specific fatty acid and amino acid needs of infants.  Clinical studies of fatty acid needs focus on the effect of 3 vs. 6 fatty acids on energy balance and the mechanism(s) by which these two families of fatty acids exert effects.  Concurrent studies in animals focus on the effects of specific 6 and/or 3 fatty acids on cellular and molecular events controlling nutrient utilization and, hence, energy balance. Clinical studies of amino acid needs focus on the role of aromatic amino acids in supporting the acute-phase protein response of various groups of stressed infants. The need for tyrosine, particularly by infants who require parenteral nutrition, is of specific interest. Studies of fatty acid needs are being conducted collaboratively with Dr. Craig L. Jensen of the CNRC and Dr. Steven D. Clarke of the University of Texas at Austin. Those studies concerning amino acid needs are being conducted collaboratively with Dr. Farook Jahoor of the CNRC.

Karen Hirschi, Ph.D.
Blood vessel formation is essential for normal growth and development. It plays a central role in the progression of prevalent pathologies including atherosclerosis, tumor angiogenesis and diabetic retinopathy. Dr. Karen Hirschi is interested in understanding how blood vessels are assembled, elucidating the regulators of cellular recruitment, proliferation and differentiation needed for vessel formation and maintenance, and exploring the role of such effectors in prevention and treatment of vascular pathologies.  She is specifically interested in elucidating the role of nutrients in the direct modulation of vascular cell growth and mural cell differentiation via cell cycle-associated, and mural-cell-specific, gene regulation.  She is also interested in the indirect modulation of vascular cell differentiation and growth via nutrient regulation of cell-cell junctional components such as extracellular matrix and gap junctions.These issues are being addressed using novel in vitro coculture systems, murine embryo culture, and transgenic mouse models.

Kendal Hirschi, Ph.D.
Unable to flee when challenged by an environmental threat, plants must adapt by altering their physiology. Calcium ions play a central signaling role in the cascade of events that empower plant cells to initiate these responses. Dr. Kendal Hirschi has utilized mutants in budding yeast to isolate plant genes that regulate intracellular calcium levels. Future work in his lab will be directed toward molecular and genetic approaches to study calcium transport and signaling in the model plant Arabidopsis thaliana.

Judy A. Hopkinson, Ph.D.
Dr. Hopkinson's research is focused on body composition changes during reproduction, and the effects of those changes on pregnancy outcome, lactation performance, and maternal weight retention. Maternal energy balance is computed from measures of food intake, energy expenditure, energy deposition during pregnancy, and milk production during lactation. Maternal body composition changes are monitored for 2 years postpartum.  Dr. Hopkinson continues to study maternal factors that influence milk production and composition: preterm delivery, frequency of nursing, smoking, and alcohol consumption.  

Kazumi Ishimura-Oka, M.D.
Dr. Ishimura-Oka's major interest is lipoprotein metabolism. She has recently generated transgenic mice which express lipoprotein lipase (LPL), a pivotal enzyme of lipoprotein metabolism. In this animal model, LPL is expressed only in adipose tissue. Using this animal model, her laboratory will determine the tissue-specific effects of LPL in lipid metabolism with regard to metabolic disorders such as obesity, atherosclerosis and non-insulin-dependent diabetes mellitus.

Farook Jahoor, Ph.D.
Dr. Jahoor's research focuses on the intermediary metabolism of macronutrient fuels. One area of primary interest is the altered metabolic response to the stress of infections, and its impact on nutritional requirements during early growth and development. Studies are being performed in both animals and humans to determine how stress alters protein (and specific amino acids), carbohydrate and lipid metabolism.  Another area of research looks at how the production of antioxidants and proteins involved in the immune response is affected by conditions such as protein-energy malnutrition, HIV infection, aging and diabetes mellitus. Specific studies focus on the metabolism of glutathione, cysteine, acute-phase proteins and nitric oxide. Stress-induced changes in the partitioning of nitrogen for the synthesis of muscle proteins, acute-phase proteins and nutrient transport proteins are also being investigated. Dr. Jahoor is also involved in the development and use of different stable isotope tracer methodologies to investigate intermediary metabolism.

Craig L. Jensen, M.D.
Dr. Jensen's research is directed toward determining the optimal intakes of polyunsaturated fatty acids for term and preterm infants. The ability of infants to synthesize longer-chain n-3 and n-6 polyunsaturated fatty acids from their precursors,  -linolenic and linoleic acids, respectively, is being investigated using stable isotope techniques. The effects of different dietary intakes of essential fatty acids on biochemical and functional outcomes in both term and preterm infants are being assessed.