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

 
   

   

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.
Dr. Haymond’s research focus 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 increasing incidence of both type I and type II diabetes provides unique opportunities to study the effects of insulin, insulin resistance and obesity on macronutrient assimilation in children. Specific studies utilize a variety of stable isotopic tracer techniques to estimate insulin sensitivity, absorption of carbohydrates, proteolysis, protein synthesis, gluconeogenesis, carbohydrate disposal, and protein and fat metabolism. Studies currently under way explore the impact of diet composition (fat and carbohydrate) on glucose homeostasis and macronutrient accretion in normal and obese children, the impact of lactation on glucose homeostasis, the precursors for lactose production by the mammary gland as well as the factor(s) which regulate it, and the regulation of galactose and fructose metabolism and the effects of co-ingestion of glucose.

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 K. Hirschi, Ph.D.
Blood vessel formation is essential for normal growth and development, and 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 also interested in examining the potential of stem cells derived from adult tissues to give rise to vascular cells in vivo, and utilizing such cells to enhance or suppress normal and pathological neovascularization. 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 goal is to define physiological and behavioral factors associated with optimal breastfeeding practices. To achieve this goal, her research focuses on the following areas: the impact of lactation on maternal and infant physiology, with special emphasis on bone metabolism; the identification of cultural factors that limit breastfeeding duration and/or exclusivity; the characterization and etiology of breast and nipple discomfort encountered by breastfeeding women; and the evaluation of intervention strategies and counseling techniques designed to increase optimal breastfeeding behaviors.

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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, alpha-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.

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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.

Gerard Karsenty, M.D., Ph.D.
Dr. Karsenty’s research focus is on the regulation of bone remodeling by hormones that also affect body weight and reproduction. To that end, Dr. Karsenty is using mutant mouse strains in which either specific hormones or their receptors are deleted. He currently is studying how leptin controls bone mass. He hopes to determine whether leptin acts through a different set of secondary messengers to regulate body weight and bone mass, using mouse models generated in the laboratory. He also is exploring the concept that antagonizing the leptin pathway may be a way to treat osteoporosis without affecting body weight. Lastly, he is studying other hormones that may regulate body weight and bone mass.

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Alexandre Lapillonne, M.D., Ph.D.
Dr. Lapillonne’s primary research interest is to determine if, and how, an early nutritional event may have long-term effects on quality of growth, metabolic functions and development. His work has focused on the most common nutritional problems during early life: the effect of intrauterine growth on body composition and postnatal growth; the effects of specific nutrients on gene transcription; and how alterations in gene transcription affect growth and body composition. His current research focuses specifically on the effect of n-3 polyunsaturated fatty acids on weight gain, body composition, fat oxidation, energy expenditure and transcription of genes controlling lipid oxidation and thermogenesis. A planned project will assess how and when in early life, optimization of protein intake will maximize catch-up growth and neurological development of very-low-birth-weight infants. Each project employs a wide variety of tools of in vivo investigation (e.g., indirect calorimetry, body composition assessment, stable isotope methodologies) as well as in vitro methods such as DNA microarray analysis. The overall goal of Dr Lapillonne’s research is to optimize the nutritional management of extremely low-birth-weight infants in order to overcome long- lasting effects on growth and development.

Carlos Lifschitz, M.D.
Dr. Lifschitz currently is conducting a multicenter study aimed at determining the effect of growth hormone on intestinal adaptation in children with short bowel syndrome. His future plans include the initiation of a Houston study that will focus on the relationship between food allergy and gastrointestinal dysfunction in children.

Ronald L. McNeel, M.S.
Ronald McNeel studies the influence of long-chain fatty acids on adipocyte growth and differentiation. These studies focus on the in vitro use of isolated stromal-vascular cells to evaluate factors regulating the differentiation process in the presence of long-chain fatty acids. Mr. McNeel is studying the binding affinities of these long-chain fatty acids to the ligand-binding region of the PPAR-RXR heterodimer. The goal is to further characterize the molecular mechanisms by which fatty acids influence adipocyte differentiation. In a second research area, Mr. McNeel is studying the association of polymorphisms in adipocyte-specific genes with obesity measures, using a case-control epidemiological design.

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/EBP-alpha or PPAR-gamma) 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 Nichols, M.D.
The ultimate objective of the research being conducted by Dr. Buford Nichols is the determination of the mechanisms by which dietary starch interacts with the gene expressing maltase-glucoamylase. Maltase-glucoamylase is the gatekeeping enzyme that determines small intestinal starch digestion into glucose or, by default, colonic fermentation into short-chain fatty acids. The function and regulation of maltase-glucoamylase are under investigation in knockout mice and children with deficient starch digestion. The mechanism of regulation is under study in a mouse intestinal cell line producing maltase-glucoamylase.

Theresa A. Nicklas, Dr. P.H.
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-American and Hispanic-American preschool children attending Head Start.

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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