 2002
Faculty Research Summaries
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Dr. Abrams' research focuses on the mineral nutritional
needs of infants, children and adolescents. His first major
area of interest is in calcium and bone mineral requirements
of children. The goal of this work is to evaluate methods
for optimizing bone mass in childhood, using stable isotopes
to measure calcium absorption and bone kinetics. His second
area of interest is in identifying the optimal forms and amount
of iron and zinc to provide to small children, especially
those who live in developing countries. In these countries,
iron deficiency anemia and zinc deficiency are extremely common
and strategies must be developed for fortifying food sources
and providing complementary foods with adequate amounts of
bioavailable minerals. His team frequently travels to other
countries to assess these issues and assist in developing
research programs using iron and zinc stable isotopes.
Dr. Anderson’s research is aimed at promoting regular
physical activity by understanding its determinants, including
self-identity as a motivational factor in health behavior.
A primary focus is the description and measurement of athletic
identity and its relation to physical activity in children,
adolescents, and parents, as well as factors that contribute
to identity formation, stability, and change. Another focus
of her research is the development of psychometrically valid
and reliable measurement instruments of attitudes and behaviors,
as well as the statistical evaluation of existing measurement
instruments that are used in behavioral research.
Ms. Baranowski is interested in dietary and physical activity
health promotion, and obesity and chronic disease prevention
among children and their families. She designs, implements
and evaluates programs to help children and their families
change dietary and physical activity behaviors. Ms. Baranowski
currently is co-principal investigator on an obesity prevention
project among African-American girls, a diet and physical
activity badge program for Boy Scouts, and an investigation
of influences on availability of fruit, juice and vegetables
in the home.
Dr. Baranowski is interested in obesity and chronic disease
prevention among children and their families. Toward this
end, he develops and tests new measures of diet and physical
activity; assesses correlates of diet and physical activity;
and designs, implements and evaluates programs to help children
and their families change dietary and physical activity behaviors.
He currently is principal investigator on an obesity prevention
project among African-American girls, a diet and physical
activity badge program for Boy Scouts, a diabetes prevention
trial among middle-school students, and an investigation of
influences on availability of fruit, juice and vegetables
in the home.
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.
Dr. Burrin’s major research goal is to elucidate the
critical cellular and hormonal signals that mediate the stimulatory
effects of enteral nutrition on the growth and function of
the neonatal intestine. Current studies are aimed at establishing
the physiological and clinical significance of GLP-2 and enteral
nutrition, and how they impact intestinal nutrient metabolism
in his neonatal pig model. He is using isotope tracers coupled
with arteriovenous organ balance and blood flow measurements
in neonatal pigs to quantify the intestinal absorption and
metabolism of macronutrients provided either enterally or
parenterally. Using these approaches, he is examining amino
acid and oxidative substrate metabolism in piglets fed parenterally,
and evaluating whether this is altered by GLP-2 treatment.
He will test whether the trophic effects of GLP-2 treatment
during total parenteral nutrition translate into enhanced
gut function. Additionally, he is investigating the underlying
mechanisms of enteral nutrition and GLP-2 action at the tissue
and cellular level. These studies are aimed at determining
how these nutritional and hormonal factors modulate the rates
of cellular protein turnover, proliferation and programmed
cell death of mucosal epithelial cells. Dr. Burrin plans to
identify how these factors affect the expression and activity
of key signaling intermediates in these cellular pathways.
Genetic and environmental causes of childhood obesity are
the current focus of Dr. Butte’s research. A genomic
scan for loci associated with the development of obesity is
being performed in 1,600 Hispanic individuals from 300 nuclear
families. Extensive phenotyping of the children includes measurements
of body composition, food intake, eating behavior, energy
partitioning during growth, energy expenditure, physical fitness
and activity, and serum hormones and metabolites. Extensive
research on the food intake, energy expenditure and body composition
of infants and children preceded this work on childhood obesity.
Other major interests include the functional consequences
of variations in energy balance on pregnancy outcome, postpartum
weight retention, lactation performance, and infant growth
and development.
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.
Dr. Conneely’s research focuses on establishing the
role of the iron-binding protein, lactoferrin (LF), in the
regulation of homeostasis, growth and development of the gastrointestinal
tract and in protection against bacterial infection and inflammation.
Lactoferrin is a multifunctional protein found at very high
levels in milk and in the body secretions that interface with
the external environment. The second most abundant protein
in human breast milk, LF is inactivated in infant formulae.
Dr. Conneely’s studies indicate that LF is not required
for intestinal iron uptake, but plays a critical role in preventing
against excessive iron absorption in mice. Dr. Conneely has
generated a mouse deficient in LF to establish the essential
physiological functions of this iron-binding protein. As described
above, she has uncovered a critical temporally restricted
function of LF in the prevention against excessive iron uptake
during the neonatal period of development. She plans to continue
her studies on the neonatal iron sequestration role of LF,
and to examine its role in prevention against bacterial infections.
She also will examine the consequences of LF ablation on intestinal
inflammation, using mouse models of Crohn’s disease
and ulcerative colitis.
Dr. Cooney’s research goal is to understand the mechanism
of action of the transcription factor GCNF in regulating embryonic
gene expression, and the influence of the maternal diet on
its activity. To achieve this objective, his research focuses
on identifying GCNF- responsive target genes expressed during
embryogenesis and studying the GCNF mode of regulation of
these genes. To date, he has been able to identify Oct4 as
a GCNF- responsive gene that is silenced in somatic cells
after gastrulation by GCNF. Using a yeast two-hybrid screen,
he has identified DNA methyl transferases as interacting partners
of GCNF. Methylation of DNA around genes has been implicated
in the silencing of genes, so this would be the first example
of regulated and targeted DNA methylation by specific recruitment
of a DNA methyltransferase. His laboratory is using knockout
mouse models and the multipotent embryonic carcinoma cell
P19 to study GCNF’s regulation of Oct4 expression via
DNA methylation.
Dr. Cullen’s research focuses on the prevention of
diet-related chronic diseases through the development, implementation,
and evaluation of nutrition behavior change programs for children
and adolescents. Of particular interest are programs aimed
at increasing children’s fruit and vegetable consumption,
utilizing unique delivery channels. Current projects include
implementing and evaluating an environmental behavior change
program for middle-school cafeteria a la carte/snack bars
that includes social marketing within the cafeteria environment;
developing and implementing a school-based program for the
prevention of type 2 diabetes among youth; and conducting
a feasibility study on an Internet-based dietary behavior
change program aimed at families.
Dr. Davis' research goal 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: the role of insulin and amino acids in the regulation
of protein synthesis in the neonate; the role of insulin and
amino acids in the regulation of the insulin signaling pathway
which leads to translation initiation in the neonate; the
role of hormones, cytokines, and nutrients in the regulation
of muscle protein synthesis during sepsis in the neonate;
and the role of insulin and nutrient intake in the anabolic
response to growth hormone.
Two focal points of interest of Dr. Debby Demory-Luce are
the eating habits of preschool children, and pediatric nutrition
education for primary care providers. A current research area
involves the examination of how preschool children’s
eating habits are affected by environmental factors and their
parents’ personal characteristics, such as weight and
health-related beliefs.
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 regulation of muscle growth rate during early postnatal
life and its impact on muscle function in adulthood comprise
the focus of Dr. Fiorotto’s research. The major objective
of the work is to identify how the developmental stage of
the tissue influences both the short- and the long-term response
of the muscle to two of the primary regulators of muscle growth:
nutrient availability and endocrine factors [growth hormone-releasing
hormone (GHRH), growth hormone, and insulin-like growth factors.]
In addition to overall growth and body composition effects,
the responses that are being examined include the rate of
muscle protein turnover, the expression of muscle-specific
protein genes and transcription factors, satellite cell replication
and accretion. To carry out these studies, Dr. Fiorotto uses
a variety of animal models, including transgenic mice with
altered muscle growth and growth factor expression, as well
as gene-transfer techniques in which an exogenous gene for
GHRH is administered postnatally, or prenatally to the mother,
to drive the long-term expression of the hormone.
Dr. Fisher’s research investigates the development
of food preferences and the controls of food intake during
infancy and early childhood. The broad goal of her research
program is to understand how early eating environments modify
young children’s eating behavior and health outcomes.
Of particular interest is parents’ role in selecting
foods of the family diet, in serving as models of eating behavior,
and in making child feeding decisions that affect child food
preferences, selection, and intake patterns. Currently, studies
are being conducted to understand the influence of maternal
feeding practices on the development of food intake regulation
and growth during infancy. Another line of research evaluates
the role of maternal feeding practices and family eating styles
in problematic food intake regulation and overweight among
Hispanic children. A new project will assess the effects of
large portions on daily intake in young children and their
mothers.
Dr. Griffin’s work focuses on understanding the mechanisms
by which humans regulate zinc metabolism, particularly the
metabolic adaptations to low zinc intakes, and the importance
of marginal zinc status in human disease (e.g., Crohn’s
disease.) His research uses stable (nonradioactive) isotopes
and mathematical modeling techniques to describe zinc metabolism
in health and disease.
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.
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.
Dr. Haney’s current long-term research goal is to understand
the molecular cell biology of lactation. Current work focuses
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. He has shown
that GLUT1, normally a plasma membrane protein, is diverted
to the intracellular site of lactose synthesis in lactating
mammary epithelial cells, suggesting that these cells have
a unique, hormonally and developmentally regulated, and nutritionally
important mechanism to alter GLUT1 targeting. Efforts are
under way to elucidate this mechanism by identifying structural
determinants of intracellular GLUT1 targeting in mammary epithelial
cells. Video confocal microscopy demonstrates that intracellular
GLUT1 targeting is highly dynamic and can be altered with
certain drugs. Dr. Haney is also examining how GLUT1 gene
expression and subcellular targeting regulate the synthesis
of lactose. This work should ultimately help to understand
and influence lactational performance in women, thereby promoting
successful breastfeeding.
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
isotope 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.
Dr. Heird’s studies focus on the nutrient needs of
low-birth-weight infants and other infants and children with
special needs, including the specific amino acid needs of
those who depend upon parenterally delivered nutrients, as
well as ways of meeting these needs. An additional interest
concerns the metabolism of essential fatty acids during infancy
and childhood and the role of long-chain polyunsaturated fatty
acids in infant development.
Dr. Karen Hirschi’s primary research interest is to
understand, at the cellular and molecular level, the events
leading to blood vessel formation. She is interested in elucidating
regulators of vascular cell (endothelial and smooth muscle)
recruitment, proliferation and differentiation needed for
blood vessel assembly and maintenance. One aim is to define
mechanisms by which soluble effectors, such as retinoids and
TGF-beta, and cell-cell junctional components, such as gap
junctions, modulate vascular cell phenotype and cell cycle
progression. Another focus is to investigate the potential
of adult stem cells to contribute to neovascularization in
response to tissue injury and growth. The mechanisms by which
adult stem cells are recruited, induced to differentiate into
vascular cells, and functionally integrated into existing
vascular networks, are of particular interest. Insights gained
from such cell and developmental studies are applied to the
optimization of clinically relevant treatments, including
autologous vascular cell and gene therapy, assembly of blood
vessels grafts, and vascularization of engineered tissues.
Plants cannot run from environmental stresses; they must
adapt. Dr. Kendal Hirschi is studying the mechanisms by which
plants sequester nutrients and toxic metals into the plant
vacuole to cope with environmental challenges. At the molecular
level, his goal is to understand the structure, biological
function, and regulation of transporter proteins that control
trafficking into and out of the plant vacuole. Another major
goal is to learn how to manipulate the expression and function
of these transporters to increase the nutritional content
of crop plants, improve plant productivity, and cleanse polluted
soils. He views these objectives as integral components of
the Green Revolution, the global agricultural movement whose
aim is to end world hunger by developing innovative ways of
increasing grain yields, particularly via the use of genetically
improved food plant varieties.
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.
Dr. Jahoor's research focuses on the metabolic alterations
of specific nutrient transport and acute-phase proteins, amino
acids, carbohydrate and lipids in response to different pathologies,
including undernutrition, diabetes mellitus and chronic infections.
He also studies glutathione metabolism and its relationship
to oxidant damage of lipids and proteins in conditions of
increased oxidant stress.
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.
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. 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.
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.
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 McNeel studies the pathways and nutritional controls
of differentiation in preadipocytes as they relate to the
pathological condition of obesity. Obesity research studies
center on a key transcription factor that is the key regulator
for adipocyte differentiation and proliferation, peroxisome
proliferator-activated receptor g (PPARg2). These research
studies are not limited to the effects of PPARg2, but are
inclusive of other transcription factors that regulate PPARg2
and thereby influence adipocyte differentiation. Of key importance
is the contribution of nutritional factors as they relate
to differential regulation of preadipocyte differentiation
through these transcription factor pathways that include PPARg2.
Another area of research investigates the association between
multiple candidate gene variations and quantitative measures
of body size and fat in populations. Analysis includes gene-gene
and gene-environment interaction.
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.
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.
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.
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.
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 (KO) mice and children
with deficient starch digestion. The most recent discovery
is the presence of a spliced secreted isoform, which participates
in starch digestion in the lumen of the ileum of KO mice.
This secreted isoform of the enzyme is produced in the goblet
cells instead of enterocytes. The mechanism of regulation
of both isoforms is under study in a mouse intestinal cell
line producing maltase-glucoamylase in wild-type and null
MGA mice on different starch diets.
The research conducted by Dr. Nicklas focuses on 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 environmental factors
influencing the development of eating patterns early in childhood;
how these eating patterns relate to the onset of obesity,
cardiovascular disease, cancer and type 2 diabetes; and effective
intervention strategies for changing and maintaining healthful
behavior changes, particularly in children and adolescents.
Current areas of research include a detailed investigation
of the relationship among eating patterns, diet quality, and
obesity in children and young adults; an examination of environmental
influences on fruit, juice, and vegetable consumption and
body mass index of Head Start preschool children; and development
of a valid and reliable computerized food preference measure
for use with preschool children. Planned studies include a
behavior-based intervention aimed at favorably influencing
food preferences and consumption by African-American and Hispanic-American
preschool children attending Head Start; and a behavior-based
family intervention designed to increase fruit, fruit juice,
and vegetable consumption by preschool children.
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.
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.
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.
Partha Sen, Ph.D.
Dr. Partha Sen is the director of the Child Health Research
Center (CHRC) Molecular Core Laboratory. The laboratory provides
DNA sequencing and DNA synthesis services to the CHRC awardees
and their mentors and Baylor faculty at large. Dr. Sen is
also involved in research related to alveolar capillary dysplasia
(ACD). This is a genetic disorder which causes misalignment
of lung blood vessels, and is also characterized by a severe
reduction of capillaries in the lungs of the patient. The
relentless course of the disease culminates in the death of
the neonate despite intensive therapy. The inheritance of
the disease is presumed to be autosomal recessive. The study
is being done in collaboration with Dr. C. Langston, Department
of Pathology, Baylor College of Medicine, and Dr. B. Bejjani,
Department of Human Genetics, Baylor College of Medicine.
The primary goal of the research project is to identify the
causative gene for this human disorder.
Dr. Shulman is investigating the factors regulating the
development of gastrointestinal function in the premature
infant. He is interested particularly 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. The long-term
goal is to understand and, thereby, be able to treat feeding
intolerance in premature infants. These data also can be applied
to treat infants with short bowel syndrome. Most recently,
he has been broadening his research efforts, and has initiated
studies to understand the factors that contribute to health
care-seeking behaviors in children with recurrent abdominal
pain.
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.
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.
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, the design of
research protocols, statistical analysis, interpretation,
and manuscript preparation. His support services range from
basic consultation to extensive involvement in a project.
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 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.
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 with regard to conditions such as Rett syndrome,
but may also provide a better understanding of 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.
Dr. Wong’s main research interests include strategies
to prevent childhood obesity and the use of dietary supplementation
to prevent chronic diseases. Based on the data that he collected
in the Houston Independent School District to document the
prevalence and risk factors of childhood obesity, a grant
application designed to determine the appropriateness and
effectiveness of an after-school physical activity program
to prevent obesity among Hispanic children has been submitted
to the National Institutes of Health. With respect to projects
related to the use of dietary supplements to prevent chronic
diseases, Dr. Wong is the project director of a USDA-funded,
multicenter, 2-year follow-up, randomized, double-blind, placebo-controlled
study to determine the safety, efficacy, and optimal dosage
of soy isoflavones to prevent osteoporosis in postmenopausal
women. Dr. Wong also is the principal investigator of a project
to determine the effects of soy isoflavones on nitric oxide
production and blood pressure in postmenopausal women with
high-normal blood pressure. This project has received a score
of 156 from the National Institute of Aging. Dr. Wong serves
as the director of the Gas-Isotope-Ratio Mass Spectrometry
Core Laboratory, the chairman of the Space and Equipment Committee,
and the chairman of the Equipment Maintenance/Repair Program
at the USDA/ARS Children’s Nutrition Research Center.
He has been appointed by the Texas Board of Health to serve
on the Texas Department of Health Osteoporosis Advisory Committee
between January 1, 2001 and December 31, 2006.
Dr. Zakeri is interested in Nutimetrics, the application
of statistical methods to problems in nutrition. His goal
is to advance, develop and apply more accurate and computationally
flexible statistical techniques to analyze and better understand
many complex problems in nutrition, particularly behavioral
nutrition. His primary research interests in statistics are
time series analysis, multivariate analysis, sequential analysis,
and statistical pattern recognition.
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