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USDA/ARS Children's Nutrition Research Center at Baylor College of Medicine

 
   

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Faculty Research Summaries

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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.

Tom Baranowski, Ph.D.
Janice Baranowski, M.P.H., R.D., L.D.
Eating larger amounts of fruit, 100% juice and vegetables has been shown to provide protection from several chronic diseases, and may enhance weight control. Eating practices are learned in childhood. The focus of the Baranowskis' research is on theory-based programs aimed at determining how to help children eat more fruit, 100% juice and vegetables. The results of several of their community-based nutrition education research projects were published, submitted or completed during the year 2000, including "GIMME 5," a school-based class curriculum intervention; "5 A Day Boy Scout Achievement Badge;" "Squire's Quest!," a school-based, interactive, multimedia, nutrition education game; and "Bringing It Home," a school-based program designed toward influencing the parents of 4th-grade children. All the individuals targeted by these programs showed some change in dietary behavior. The researchers also demonstrated that an interactive, multimedia program for dietary assessment among 4th-grade children worked almost as well as a dietitian-conducted, 24-hour dietary recall. The Baranowskis currently are actively involved in the Houston-area "Fun, Food and Fitness Program," which is part of the national Girls' Health Enrichment Multi-site Study (GEMS), aimed at the prevention of obesity in 8-year-old African-American girls.

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.
Dr. Burrin's major research objective is to elucidate the cellular and hormonal signals that mediate the stimulatory effects of enteral nutrition on the growth and function of the neonatal intestine. Recent studies have established the quantity and quality of enteral nutrients necessary for maintaining normal intestinal growth and function. He has found that the neonatal intestine utilizes a substantial proportion of the dietary nutrients to maintain normal growth. He has also found that the secretion of the gut-derived peptide, glucagon-like peptide 2 (GLP-2), is closely correlated with enteral nutrient intake, and that infusion of GLP-2 produces intestinal trophic effects when given to neonatal pigs. In contrast, treatment with dexamethasone has a potent catabolic effect on the neonatal intestine. Future studies will investigate the physiological significance of GLP-2, and how it affects intestinal protein and amino acid metabolism in neonatal pigs. He will examine whether the catabolic effects of dexamethasone compromise intestinal absorptive function, and how the provision of either minimal enteral nutrition or GLP-2 ameliorates the actions of dexamethasone. To understand how these nutritional and hormonal factors modulate intestinal growth, he will quantify the rates of cellular protein turnover, proliferation and programmed cell death. How these factors affect the expression and activity of key intermediates in these cellular pathways will be identified.

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 that 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.

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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 isotope-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.

Orla M. Conneely, Ph.D.
The objective of Dr. Conneely's research is to establish the role of nuclear receptors in vertebrate development. Nuclear receptors comprise a large family of structurally related transcription factors regulating the expression of genes that control a variety of developmental and physiological responses to diverse stimuli.

Austin J. Cooney, Ph.D.
The focus of Dr. Cooney's research is to analyze the mechanism of action of the orphan nuclear receptor GCNF in embryonic development mediated through repression of essential developmental genes, such as Oct4. Currently, he is attempting to show that the mechanism of gene repression by GCNF is mediated through the DNA methylation machinery. He is also trying to determine the effects that maternal diet plays in modulating these effects on DNA methylation patterns and gene expression mediated by GCNF. His long-term goal is to understand the role of GCNF, DNA methylation and maternal diet on the susceptibility to adult diseases.

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.

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Teresa A. Davis, Ph.D
The goal of Dr. Davis' work is to identify the mechanisms by which hormones and nutrients interact to regulate the high rate of skeletal muscle protein deposition in the neonate. To achieve this objective, her research focuses on four main areas: 1) the role of insulin and amino acids in the regulation of protein synthesis in the neonate; 2) the role of insulin and amino acids in the regulation of the insulin signaling pathway which leads to translation initiation; 3) the effect of sepsis on insulin-stimulated protein synthesis; and 4) the role of insulin and nutrient intake in the anabolic response to growth hormone     

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 nuclear?based 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 age?related 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.

Jennifer Orlet Fisher, Ph.D.
Dr. Fisher investigates the development of food preferences and the controls of food intake during infancy and early childhood. Her work has focused on understanding how early eating environments modify young children's eating behavior and health outcomes. Of particular interest is the role of the parents in selecting foods of the family diet, in serving as models of eating behavior, and in making child feeding decisions. Dr. Fisher's research has shown that restrictive feeding practices may favor the development of childhood overweight by focusing children's attention on restricted foods and promoting children's intake of those foods in the absence of hunger. Currently, she is conducting research that evaluates children's responsiveness to increasing portion sizes, and aims to determine whether repeated experience with large portion sizes affects children's learning about what constitutes a normal portion. Future projects will evaluate the roles of maternal dietary choices and infant feeding practices with regard to food preferences, the regulation of food intake, and development of overweight during infancy.

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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 nutrient transport in plants. His long-term goals are to characterize the dynamics of nutrient flow within plants in order to determine the biophysical/molecular signals that regulate source-to-sink nutrient partitioning, and ultimately to use this information to enhance the nutritional quality of plant foods for human consumption. With regard to his human nutrition research, his laboratory group has developed hydroponic growth facilities and various protocols to intrinsically label plant foods with stable isotopes of important nutrients; these are then 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 studies focus on the nutrient needs of low-birth-weight infants and other infants and children with special needs as well as ways of meeting these needs, including the specific amino acid needs of those who depend upon parenterally delivered nutrients. An additional interest concerns the metabolism of essential fatty acids during infancy and childhood, including the role of long-chain polyunsaturated fatty acids in this population.

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. 

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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.

Heidi Karpen, M.D.
Dr. Karpen's research involves the study of Patched, a tumor suppressor gene responsible for Gorlin Syndrome. Patched is a member of the Sonic Hedgehog signaling pathway, critical for early embryonic patterning and development. Dr. Karpen is using mutations identified in Gorlin patients and sporadic basal cell carcinomas to define functional domains important for protein trafficking and function. The goal of this research is to better understand mechanisms of aberrant embryonic development and cancer formation so that targets for intervention may be identified.

Carlos Lifschitz, M.D.
Dr. Lifschitz has several research interests. First, he is conducting a multicenter study aimed at determining the effect of growth hormone on intestinal adaptation in children with short bowel syndrome. A second research interest involves the effect of nutrients on gut function. Dr. Lifschitz will be one of the investigators involved in a study in Botswana, South Africa, aimed at determining the effect of two levels of nucleotide supplementation on HIV-positive infants. A third interest involves food allergies. Dr. Lifschitz plans to conduct a Houston-area study on the relationship between food allergy and gastrointestinal function in children.

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Ronald L. McNeel, M.S.
Mr. McNeel's research interests involve studies of the influence of various fatty acids (e.g., conjugated linoleic acid) on adipocyte growth and differentiation in the human.  These studies focus on the in vitro use of isolated human stromal cells to evaluate factors regulating the differentiation process in the presence of fatty acids.  Transcript concentrations for transcription factors that regulate differentiation (C/EBP, PPAR, and ADD1) and transcript concentrations for key proteins that characterize the adipocyte (LPL, leptin, and aP2) are measured. These measurements help to characterize the mechanisms by which fatty acids influence adipocyte differentiation. A second research area involves studying the binding kinetics of fatty acids to the PPAR-RXR heterodimer. 

Harry J. Mersmann, Ph.D.
Adipocyte growth and differentiation are regulated by various hormones and growth factors. Beta-adrenergic receptors are among the major regulators of adipocyte metabolism. Dietary components may alter the pattern of adipocyte growth and differentiation. Dr. Mersmann's laboratory has studied the influence of the stage of development and of dietary factors on adipocyte beta-adrenergic receptors. Currently, the focus of his efforts is on adipocyte development. Porcine adipocyte precursor cells may be isolated from adipose tissue and when grown in culture in vitro under the proper conditions, differentiate to adipocytes. He has used this system to evaluate factors regulating the differentiation process and the influence of dietary components of differentiation. In addition to mRNA for the beta-adrenergic receptors, mRNA for various transcription factors that regulate differentiation (e.g., C/EBPa or PPAR) and mRNA for key proteins that characterize the adipocyte (e.g., lipoprotein lipase and aP2) are being measured. He is particularly interested in the role of individual fatty acids in the stimulation or inhibition of adipocyte differentiation.

David D. Moore, Ph.D.
The receptors for retinoic acid, thyroid hormone, steroids, and other potent biological regulators belong to a nuclear hormone receptor superfamily. This family also includes a number of additional proteins called orphan receptors, which do not have known ligands. The conventional receptors regulate a variety of processes in developing and adult animals. The orphans are less well characterized, but it is thought that they also play important roles in diverse areas. The broad-ranging effects of these proteins are a consequence of their function as ligand-dependent, or in some cases, ligand-independent transcription factors. The main goal of Dr. Moore's laboratory is to understand the mechanisms of action of the members of this superfamily. Toward this aim, he has identified a number of proteins that interact with both conventional and orphan receptors, and he is characterizing their functions.


Kathleen J. Motil, M.D., Ph.D.

Dr. Motil's studies focus on estimating dietary protein and amino acid needs of lactating women and adolescents and elucidating the mechanisms that underlie increased nutrient needs for milk production. Using stable isotope techniques, she has found that lean body mass of adult women is preserved during lactation because of the downregulation of rates of whole body protein turnover, synthesis and degradation, suggesting that nutrient conservation occurs because of the needs of milk production. In contrast, lean body mass of adolescents increases during lactation at the expense of a reduction in milk production. Dr. Motil's studies also focus on estimating the dietary protein and energy needs of girls with Rett syndrome and elucidating the mechanisms that underlie the universal finding of growth failure in this disorder. Using stable isotope techniques and whole-room calorimetry, she has found that involuntary motor movements associated with Rett syndrome do not increase rates of energy expenditure, and that poor growth results from reduced dietary energy intakes associated with oropharyngeal and gastroesophageal dysfunction.

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Paul Nakata, Ph.D.
Calcium in plants is sequestered as a complex with other substances such as oxalates, phytates, fiber, fatty acids, proteins and other anions. Some of these substances (oxalates and phytates) are considered antinutrients, and render the calcium in plant foods unavailable for nutritional absorption by the human. The purpose of Dr. Nakata's research program is to elucidate the mechanism regulating calcium partitioning and sequestration in plants. The acquired information will be applied toward the rational design of strategies to enhance calcium abundance and bioavailability in plant food products.

Buford L. Nichols, M.D.

Dr. Nichols recently cloned the cDNA of human maltase-glucoamylase (MGA) in order to begin investigations of dietary regulation of human hydrolase gene expression. Studies of protein synthesis and degradation are carried out in human biopsies by organ culture with 35S-labeled amino acids, and gene expression is investigated by quantitation of mRNA. Probes for real-time RT/PCR quantitation of maltase-glucoamylase message levels are used to study cis-regulation. Dr. Nichols has sequenced the human MGA gene in order to determine the presence of genetic polymorphisms and mutations from clinical blood DNA samples. Dr. Nichols also developed a 13C-starch loading test to determine the rate of starch digestion to glucose as a confirmatory clinical test for starch proximal malabsorption. Using a combination of these methods, Dr. Nichols recently discovered two children with apparent coding defects in MGA and five with an apparent cis-regulatory defect, which also reduces lactase and sucrase activities.

Theresa A. Nicklas, Dr.P.H., M.P.H., L.N.
Dr. Nicklas' research focuses on the epidemiological and intervention aspects of chronic disease prevention and health promotion. Specifically, how do eating behaviors and other lifestyles influence the development of chronic disease risk factors early in life? Also, what are the behavioral factors influencing the development of adverse lifestyles early in life? Areas of interest include: (1) environmental factors influencing the development of adverse eating patterns early in childhood; (2) how these eating patterns relate to the onset of obesity, cardiovascular disease, cancer and type 2 diabetes; and (3) effective intervention strategies for changing and maintaining healthful behavior changes, particularly in children and adolescents. A current area of research involves a detailed investigation of the relationship between eating patterns and obesity in children and young adults. Planned studies include an examination of family and caregiver influences on fruit, juice and vegetable consumption by preschool children from different ethnic groups, and a behavior-based intervention aimed at favorably influencing food preferences and consumption by African- and Hispanic-American preschool children attending Head Start.

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Emiel W. Owens, Ed.D.
Dr. Owens' research projects focus on development of mathematical models to access dietary and behavior patterns among children. Modeling dietary habits in children will open the door to understanding and ultimately precluding the potential causes of fatal disease in their adult years. His other work involves the evaluation of school-based nutrition programs.

Peter J. Reeds, Ph.D.
Dr. Reeds' primary work concerns the nutritional and humoral regulation of growth. He places specific  emphasis on comparative nutrition and studies of growth regulation in both animal models and humans.  He has concentrated much of his recent efforts on the study of in vivo intermediary metabolism, especially in the gastrointestinal tract, and its impact on amino acid bioavailability and requirements. He makes extensive use of stable isotopic techniques, which he applies to studies of nonessential amino acid metabolism and its relationship to the energetics of growth.

Jeffrey M. Rosen, Ph.D.
The research objectives of Dr. Rosen's laboratory are to elucidate the mechanisms regulating the normal development of the mammary gland, including the hormonal control of milk protein expression, and to determine how these regulatory mechanisms have deviated in breast cancer. Critical periods of development in the mouse mammary gland include the ductal proliferation and branching that occur during sexual maturity, lobuloalveolar proliferation that occurs during pregnancy, terminal differentiation that results in lactation, and involution characterized by increased apoptosis and extensive tissue remodeling. Studies of the role of systemic hormones (e.g., prolactin, glucocorticoids, estrogens and progestins) and local growth factors, including members of the Wnt and Fgf families, on each of these processes are under way. The roles of specific transcription factors and their dominant-negative isoforms, including members of the C/EBP, Stat and NF I families, also are being examined using transgenic and knockout mouse models. Gene arrays and subtractive hybridization techniques are employed to identify downstream targets of these transcription factors. Postnatal mammary gland development is being studied in knockout mice displaying late embryonic or neonatal mortality by transplantation of mammary epithelium into the cleared mammary gland fat pad of syngeneic recipients. In addition, methods that permit the analysis of both gain and loss of specific gene function selectively in the mammary gland have been developed. Finally, transgenic and knockout mouse models are being used to elucidate the changes in normal signal transduction pathways that are involved in the progression from the normal mammary gland to preneoplasias, as well as the role of mutant p53 in genomic instability and the development of aneuploidy.

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Hemanta K. Sarkar, Ph.D.
Dr. Sarkar's primary research interest is amino acid transport, particularly the transport of the sulfur containing the amino acid taurine, which is one of the most abundant free amino acids found in the brain, eye and muscle. Taurine is a conditionally essential amino acid, because it is required for fetal and neonatal growth and development. Taurine transport across the placental membrane, and taurine absorption by specific tissues (i.e., brain, muscles, intestine, etc.), are mediated solely via a specific plasma membrane-imbedded protein known as the taurine transporter. Current research efforts are directed toward elucidating the molecular mechanism by which the taurine transporter facilitates transport of taurine across the cell membrane, and how various cellular factors and signaling molecules modulate the function of this protein. Dr. Sarkar makes extensive use of a variety of biochemical, cell biological, and molecular biological techniques to address important physiological and clinical questions regarding cellular absorption and utilization of taurine in humans, including infants.

Richard J. Schanler, M.D.
Dr. Schanler's research focuses on clinical aspects of feeding premature infants human milk. Current investigations address the potential protection from infection and necrotizing enterocolitis afforded by human milk, the effect of stress on lactation performance, and the growth and body composition of premature infants during the first few years after hospital discharge.

Robert J. Schwartz, Ph.D.
Dr. Robert Schwartz conducts research focused on defining the molecular basis underlying the establishment and maintenance of skeletal, cardiac and smooth muscle differentiation. He has devoted considerable attention to Nkx2-5, a transcription factor instrumental in the patterning of the embryonic heart. Dr. Schwartz notes that the heart appears to develop as a modular organ, such that a distinct transcriptional regulatory program controls each anatomical region. Consistent with this notion, the heart tube can be divided into segments that form the atria, left ventricle, right ventricle, and ventricular outflow tract. Precursors of these regions of the heart appear to originate from separate lineages, which develop according to their positions along the anteroposterior axis of the embryo. Recent studies conducted by Dr. Schwartz have revealed cis-regulatory elements that direct cardiac transcription specifically in the left or right ventricular chambers and atria, and even within subdomains within the chambers. Whether this regional specificity of transcription is important for the physiologic and functional differences of the chambers of the adult heart, and how these transcriptional territories are established and maintained, are issues of intense interest to Dr. Schwartz.


Robert J. Shulman, M.D.

Dr. Shulman is investigating the factors regulating the development of gastrointestinal function in the premature infant. He is particularly interested in carbohydrate digestion and absorption and the interaction of carbohydrates with other nutrients, both as facilitators and potential inhibitors of digestion and absorption of other nutrients. He also is studying the factors that contribute to feeding intolerance, and is seeking ways to ameliorate the problems that premature infants experience with enteral feedings. Dr. Shulman recently initiated studies to understand the factors that contribute to health care-seeking behaviors in children with recurrent abdominal pain.

Roman J. Shypailo, B.S.
The unprecedented growth of technology during the past decade has created challenges for researchers. Powerful computers and data acquisition equipment enable rapid accumulation of information that requires processing. The CNRC Body Composition Laboratory houses sophisticated instruments designed to measure the elemental composition of the human body using nuclear-based techniques. Each instrument is in a dynamic state of evolution. New measurement systems are being developed, including a multiparameter whole-body counter capable of isolating and measuring a signal coming from a specific site in the body, and a portable  40  K counter for use in a hospital setting.  Coordinating these efforts and incorporating new technology are the primary focus of Mr. Shypailo's work.

C. Wayne Smith, M.D.
Dr. C. Wayne Smith, who is the head of the Leukocyte Biology Section of the Pediatrics Department as well as a CNRC researcher, has a multifaceted research focus involving the roles of neutrophils in host resistance to infection and tissue injury under conditions of inappropriate inflammation. Dr. Smith is actively involved in a number of projects with other researchers. He works with Dr. Michele Mariscalco in a project on neonatal neutrophil function; with Dr. Mark Entman of Baylor's Department of Medicine on neutrophil-mediated injury to myocardium; with Dr. Christie Ballantyne on the phenotypes of mice with CD18 subunit deficiency; with Dr. Jim Smolen on the influence of stress on leukocyte functions; and with Dr. Alan Burns on the molecular and cellular mechanisms of neutrophil transendothelial migration. Dr. Smith also is collaborating with Dr. Hartmut Jaeschke of the University of Arkansas on neutrophil-mediated liver damage. Further, Dr. Smith is working with CNRC researcher Dr. Harry Mersmann on the potential role of leukocytes in the development of obesity.


E. O'Brian Smith, Ph.D.
Dr. E. O'Brian Smith provides statistical design, analysis, and teaching support to the USDA/ARS Children's Nutrition Research Center, the General Clinical Research Center, the Pediatrics Department, and Baylor College of Medicine investigators. This support includes teaching statistical methods, development of grant applications, design of research protocols, statistical analysis, interpretation, and manuscript preparation. His support services range from basic consultation to extensive involvement in a project.

Janice E. Stuff, Ph.D.
Dr. Stuff's broad area of interest is that of nutritional epidemiology and the role of nutrition in chronic diseases and public health problems. A focus area is research on methodologies to assess dietary intakes in populations. Currently, Dr. Stuff collaborates with the USDA/ARS Delta Nutrition Intervention Research Initiative. The initial purpose of this initiative is to measure the nutrition and health status of individuals and communities in the Lower Mississippi Delta region.  Specifically, Dr. Stuff has helped in efforts to develop and validate dietary methodology in the Lower Delta, which now will be applied to assess dietary intakes in cross-sectional and longitudinal designs. Other interests include the impact of food insecurity on the health, nutritional requirements and health status of children; nutritional interventions for children in high-risk, low-income areas; and the application of research findings on mineral and caloric requirements of children to interpreting nationwide nutrition surveys and databases.

Agneta L. Sunehag, M.D., Ph.D.
The focus of Dr. Sunehag's research is carbohydrate metabolism in infants and children. In particular, she is interested in the metabolism of very premature infants during their first days of life. The aim of her studies is to determine how these infants utilize their gluconeogenic pathway to produce glucose from parenterally administered lipid and amino acid solutions. The ultimate goal of these studies is to optimize the composition of neonatal parenteral nutrition solutions to prevent both hypo- and hyperglycemia, while providing a sufficient energy intake for normal growth. Her other major research interest is to determine the effects of dietary carbohydrate and fat intakes on parameters of glucose metabolism, particularly insulin sensitivity, in obese and nonobese children. The aim of these studies is to determine whether the macronutrient content of the diet affects the development of insulin resistance and, thus, the risk of type II diabetes, and whether obese children differ from nonobese with regard to metabolic adaptation to changes in dietary carbohydrate and fat content.

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Ignatia B. Van den Veyver, M.D.

Rett syndrome is caused by mutations in a gene on the X chromosome named MECP2. This gene encodes methyl-CpG-binding protein 2, which is the molecular link between DNA-methylation and suppression of transcription of genes with methylation at their promoters. Based on the discovery that this mechanism is at the basis of this devastating neurodevelopmental disorder, Dr. Van den Veyver hypothesizes that DNA methylation may play a role in the proper downregulation of certain genes during development. There is some evidence that DNA methylation can be influenced by methyl-donor enriched diets, containing substances such as folic acid and betaine. Hence, she is investigating in cultured cells and in laboratory mice whether this treatment can alter DNA methylation and gene expression. This is not only important for conditions such as Rett syndrome, but may also provide a better understanding for the role of such agents in other prenatal-onset disorders and birth defects, for example, in the mechanism by which folic acid may prevent neural tube defects.


William W. Wong, Ph.D.

Childhood obesity is a major health problem in the United States. To determine the prevalence of childhood obesity in Texas, Dr. Wong is measuring the weight and height of approximately 8,300 students attending six elementary schools, one middle school, and one high school in the Houston Independent School District. Family surveys and student questionnaires will be used to determine the effects of gender, ethnicity, socioeconomic status, dietary habits, parental obesity, and physical inactivity on childhood obesity. Another project addresses cardiovascular disease and osteoporosis, two major health problems among postmenopausal women. Dr. Wong is attempting to determine the effectiveness and the mechanisms of soy isoflavone therapy in the prevention of high blood pressure and bone loss in postmenopausal women.

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