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Steven A. Abrams,
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.
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
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.
David M. Cohen,
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.
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.,
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,
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,
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.
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
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.
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.
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.
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.
D. Moore, 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
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
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.
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.,
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.
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
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,
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.
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.
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
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
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.
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