2003 Faculty Research
Summaries
Steven A. Abrams, M.D.
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.
Cheryl B. Anderson, Ph.D.
Dr. Anderson's
research is aimed at promoting regular physical activity
through 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.
Janice Baranowski, M.P.H., R.D., L.D.
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.
Tom Baranowski, Ph.D.
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.
Dennis M. Bier, M.D.
Dr. Bier's
primary research interest is the integrated regulation
of interorgan transport of metabolic fuels; specifically,
substrate and hormonal regulation of the macronutrient
fuels, glucose, fatty acids, ketones, and proteins/amino
acids. This work has contributed broadly to the endocrine,
nutritional and physiological regulation of endogenous
fuel availability for biochemical and nutritional functions
in otherwise healthy infants born very prematurely,
normal newborn infants born at term, growing children,
maturing adolescents, and healthy young and elderly
adults. Further, his laboratory has helped both define
and refine assessment of the altered metabolic fates
of ingested, exogenous fuels under various pathophysiological
circumstances that detrimentally change nutritional
homeostasis, for example the metabolic fuel derangements
accompanying diabetes and renal failure. In these endeavors,
his laboratory has developed and employed a wide variety
of stable isotope tracer kinetic methods that have
now become the standards in the field for quantifying
substrate flux, metabolism, precursor-product relationships,
and irreversible oxidation to exhaled or excreted end
products.
Douglas G. Burrin, Ph.D.
Dr. Burrin's
major research goal is to elucidate the critical cellular
and hormonal signals mediating the stimulatory effects
of enteral nutrition on the growth and function of
the neonatal intestine. Current studies examine the
physiological and clinical significance of GLP-2 and
enteral nutrition, and how they impact intestinal nutrient
metabolism in his neonatal pig model. Isotope tracers
coupled with arteriovenous organ balance and blood
flow measurements are used to quantify the intestinal
absorption and metabolism of macronutrients provided
either enterally or parenterally, and to examine whether
GLP-2 treatment alters amino acid and oxidative substrate
metabolism in piglets fed parenterally. Whether the
trophic effects of GLP-2 treatment during total parenteral
nutrition translate into enhanced gut function and
the underlying mechanisms of enteral nutrition and
GLP-2 action at the tissue and cellular level are also
studied to determine how they modulate mucosal epithelial
cell protein turnover, proliferation and programmed
cell death rates.
Nancy F. Butte, Ph.D.
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.
Joan
Carter, R.D., M.B.A.
Ms.
Clark's focus is the dissemination of information about
the research activities of the USDA/ARS Children's
Nutrition Research Center through print and electronic
materials describing the center's mission, organization,
and research efforts. She is editor of the CNRC's award-winning
consumer-oriented newsletter, Nutrition & Your
Child, and webmaster for the center's web site, www.kidsnutrition.org,
as well as for related faculty and research project
web sites. She also serves as the center's liaison
to the public, the media, and Baylor College of Medicine
communications personnel.
David M. Cohen, Ph.D.
Dr. Cohen's
research concerns the regulated coordination of metabolic
fluxes that is fundamental to health and sustained
by adequate nutrition. Study of the quantitative relationships
among metabolic flux rates depends on accurate measurement
of those rates, preferably in vivo. To this end, he
has investigated mathematical aspects of modeling rates
of metabolic pathways, subsequent to the administration
of isotope-labeled precursors. An important focus of
Dr. Cohen's work is the measurement of cerebral metabolism
in vivo, using nuclear magnetic resonance spectroscopy.
Currently, he is developing a new method for estimation
of the rate of cerebral glucose metabolism, with a
substantial improvement in time resolution. In the
long term, he hopes to learn more about the role of
diet in support of brain metabolism and function.
Orla M. Conneely, Ph.D.
Dr. Conneely's
research concerns 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. Studies in LF-deficient mice generated
by Dr. Conneely indicate that LF is not required for
intestinal iron uptake, but plays a critical role in
preventing excessive iron absorption 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 will also examine the consequences
of LF ablation on intestinal inflammation, using mouse
models of Crohn's disease and ulcerative colitis. Austin J. Cooney, Ph.D.
Dr. Cooney's
research goal is to understand the mechanism by which
the transcription factor GCNF regulates embryonic gene
expression, and the influence of the maternal diet
on its activity. 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.
Karen Weber Cullen, Dr. P.H.
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.
Teresa A.
Davis, Ph.D.
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
five main areas: the role of insulin, amino acids,
and glucose in the regulation of protein synthesis
in the neonate; the role of insulin, amino acids, and
glucose 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; the role of development in the
regulation of the protein synthetic response to a chronic
high protein diet; and the role of insulin and nutrient
intake in the anabolic response to growth hormone.
Debby Demory-Luce, Ph.D.
Two focal
points of interest of Dr. 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.
Kenneth J. Ellis, Ph.D.
A primary
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 counter, which monitors
40 K, a naturally occurring isotope in the human. Dr.
Ellis has continued to develop in vivo neutron activation
techniques for clinical research and postmortem examinations,
and he has extended the use of dual-energy X-ray absorptiometry
to the examination of infants and children.
Marta Fiorotto, Ph.D.
The focus
of Dr. Fiorotto's research is the regulation of muscle
growth rate during early postnatal life and its impact
on muscle function in adulthood. The major objective
is to identify how the developmental stage of muscle
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 (GHRH, growth hormone, and insulin-like growth
factors). In addition to overall growth and body composition
effects, Dr. Fiorotto is also examining the rate of
muscle protein turnover, the expression of muscle-specific
protein genes and transcription factors, satellite
cell replication and accretion. For these studies,
she uses animal models, such as 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.
Jennifer Orlet Fisher, Ph.D.
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 the role of parents 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. Finally,
experimental research is being conducted to determine
the effects of large portions on daily intake in young
children and their mothers.
Ian J. Griffin, M. B., Ch. B.
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.
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.
Insulin-like
growth factors (IGFs) are necessary for mammary gland
development and lactation. Despite this, the mechanisms
by which these peptides regulate mammary gland function
are poorly understood. The focus of Dr. Hadsell's research
is to understand the specific signaling mechanisms
through which the IGF-I receptor (IGF-IR) regulates
mammary gland development and lactation. Transgenic
and/or gene targeting strategies are used to modify
the activity of key IGF-IR signaling pathway intermediates
within the mammary gland. These strategies have demonstrated:
1) that IGF-IR regulates early mammary ductal development
through the ability to regulate cell cycle progression
within specialized structures called terminal endbuds;
2) that IGF-I also acts during lactation to maintain
mammary cell survival; 3) that specific intracellular
scaffolding proteins, termed insulin receptor substrates
(IRS), are important to both the cell survival actions
and to other potential actions of IGF-I on the regulation
of milk volume and composition during early lactation.
Peter M. Haney, M.D., Ph.D.
Dr.
Haney's 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 GLUT1, the only
glucose transporter isoform identified in the mammary
gland and in established and primary mammary epithelial
cell lines 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 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.
Morey W. Haymond, M.D.
Dr. Haymond's
research focus is to delineate and ultimately manipulate
hormone and substrate factors regulating absorption,
assimilation, mobilization, and disposal of carbohydrates
in infants and children. Nutrient availability to meet
the energy and growth needs of children is frequently
disturbed by chronic disease, infection, trauma and/or
organ failure. The increase in type 1 and type 2 diabetes
provides opportunities to study the effects of insulin,
insulin resistance, and obesity on macronutrient assimilation
in children. Specific studies utilize stable isotopic
tracer techniques to estimate insulin sensitivity,
absorption of carbohydrates, proteolysis, protein synthesis,
gluconeogenesis, carbohydrate disposal, and protein
and fat metabolism. Current studies 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, precursors for and regulation of lactose
production by the mammary gland, and the regulation
of galactose and fructose metabolism.
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, 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.
Karen Hirschi, Ph.D.
Dr. Karen Hirschi's goal 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 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 are functionally integrated
into existing vascular networks, are of particular
interest. Insights gained from such 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.
Kendal D. Hirschi, Ph.D.
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.
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.
Farook Jahoor, Ph.D.
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, sickle cell disease and chronic infections.
He also studies glutathione metabolism and its relationship
to oxidant damage of lipids and proteins in conditions
of oxidative stress.
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.
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.
Alexandre Lapillonne, M.D., Ph.D.
Dr.
Lapillonne's research interest is to determine whether,
and how, early nutritional events affect long-term
growth, metabolic function and development. His work
has focused on 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. 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. He is also planning
to assess how and when in early life, optimization
of protein intake can maximize catch-up growth and
neurological development of very-low-birth-weight infants.
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, Dr. P.H.
Dr.
McNeel studies the pathways and nutritional controls
of differentiation in preadipocytes and fat mass accretion
as they relate to the pathological condition of obesity.
Obesity research studies center on key transcription
factors that are regulators of preadipocyte differentiation,
metabolism, and proliferation, including, peroxisome
proliferator-activated receptor delta (PPAR d ), gamma
2 (PPAR g 2), and alpha (PPAR a ). These research studies
are not limited to the effects of these transcription
factors only, but are inclusive of other transcription
factors that influence preadipocyte differentiation
and adipocyte metabolism. This research is focused
on a more complete understanding of the molecular mechanisms
involved in fat mass accretion, which are critical
in the design of nutritional or pharmacological intervention
strategies aimed at decreasing nutritional obesity.
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.
Harry J. Mersmann, Ph.D.
Adipocyte
growth and differentiation are regulated by various
hormones and growth factors and may be altered by dietary
components. 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. She has found that
lean body mass of adult women is preserved during lactation,
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. 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.
Starch
from grains and tubers provide the major source of
calories in the human diet. 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 gate-keeping 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 Paneth cells instead of enterocytes.
The mechanism of regulation of both isoforms is under
study in wild type and null MGA mice on different diets.
Theresa A. Nicklas, Dr. P.H.
Dr.
Nicklas's research focuses on nutritional epidemiology
and intervention aspects of chronic disease prevention
and health promotion: specifically, how eating behaviors
and other lifestyles influence the development of chronic
disease risk factors early in life and the behavioral
factors influencing the development of adverse lifestyles
in childhood. 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- and Hispanic-American
preschool children attending Head Start, and a behavioral-based
family intervention designed to increase fruit, fruit
juice, and vegetable consumption by preschool children.
Jeffrey M. Rosen, Ph.D.
Dr. Rosen's
research objectives are to elucidate the mechanisms
regulating the normal development of the mammary gland
and to determine how these regulatory mechanisms deviate
in breast cancer. Studies of the role of systemic hormones
and local growth factors on critical periods of development
in the mouse mammary gland are under way. Transgenic
and knockout mouse models are being used to examine
the roles of specific transcription factors and their
dominant-negative isoforms, postnatal mammary gland
development, and 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. In addition, methods
that permit the analysis of both gain and loss of specific
gene function selectively in the mammary gland have
been developed.
Robert J. Schwartz, Ph.D.
Dr. Schwartz
conducts research focused on defining the molecular
basis underlying the establishment and maintenance
of skeletal, cardiac and smooth muscle differentiation.
Of special interest is Nkx2-5, a transcription factor
instrumental in the patterning of the embryonic heart.
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 appear to originate from separate lineages,
which develop according to their positions along the
anteroposterior axis of the embryo. Recent studies
have revealed cis-regulatory elements that direct cardiac
transcription specifically in the left or right ventricular
chambers and atria, which could be important for the
physiologic and functional differences of the chambers
of the adult heart.
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
that 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 primary
goal of the research project is to identify the causative
gene for this human disorder.
Robert J. Shulman, M.D.
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, initiating studies to understand
the factors that contribute to health care-seeking
behaviors in children with recurrent abdominal pain.
Roman
J. Shypailo, B.S.
The unprecedented growth of technology during
the past decade has created challenges for researchers.
Powerful computers and data acquisition equipment enable
rapid accumulation of information that requires processing.
The CNRC Body Composition Laboratory houses sophisticated
instruments designed to measure the elemental composition
of the human body using nuclear-based techniques. Each
instrument is in a dynamic state of evolution. New
measurement systems are being developed, including
a multiparameter whole-body counter capable of isolating
and measuring a signal coming from a specific site
in the body, and a portable 40 K counter for use in
a hospital setting. Coordinating these efforts and
incorporating new technology are the primary focus
of Mr. Shypailo's work.
C. Wayne Smith, M.D.
Dr. Smith's
research involves the roles of neutrophils in host
resistence to infection and tissue injury in conditions
of inappropriate inflammation. He is currently collaborating
on projects investigating neonatal neutrophil function,
neutrophil mediated injury to myocardium, the phenotypes
of mice with CD18 subunit deficiency, the influence
of stress on leukocyte functions and neutrophil mediated
liver damage, and the molecular and cellular mechanisms
of neutrophil transendothelial migration. He mentors
postdoctoral fellows investigating the development
and use of gene array technology to define gene expression
in neutrophils stimulated with IL-15; the expression
of oncostatin M by neutrophils, the stimuli that lead
to expression, and the potential effects of neutrophil
OSM on endothelial cell functions; the mechanisms of
obesity in mice that are deficient in ICAM-1; and the
contribution of leukocytes to the regrowth of corneal
epithelium. He also mentors a Ph.D. student working
on the use of artifical extracellular matrix in tissue
engineering. 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, developing
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.
Janice E. Stuff, Ph.D.
Dr. Stuff's
interest is nutritional epidemiology and the role of
nutrition in chronic diseases and public health problems.
One emphasis is to understand dietary carcinogen and
chemopreventive exposure, the genetic susceptibility
to dietary carcinogens, and their interaction as determinants
for cancer. Dr. Stuff is developing and validating
databases of N-nitroso compounds
and isothiocyanate compounds in foods in order to investigate
their role in the development and prevention of cancer.
Another interest is to investigate the role of diet,
body composition, and hormone levels in the development
of risk factors for breast cancer. Dr. Stuff also collaborates
with the USDA/ARS Delta NIRI (Nutrition Intervention
Research Initiative), an initiative designed to measure
the nutrition and health status of individuals and
communities in the Lower Mississippi Delta region,
and to develop interventions. This project also investigates
the impact of food insecurity on the health, nutritional
requirements and nutritional status of children.
Agneta L. Sunehag, M.D., Ph.D.
Dr.
Sunehag studies carbohydrate metabolism in infants
and children. In particular, she is interested in how
well very premature infants utilize the gluconeogenic
pathway to produce glucose from parenterally administered
lipid and amino acid solutions. This research is needed
in order to develop neonatal parenteral nutrition solutions
that prevent both hypo- and hyperglycemia while providing
a sufficient energy intake for normal growth. Her other
research projects are aimed at determining whether
the macronutrient content of the diet affects the development
of insulin resistance and, thus, the risk of type 2
diabetes in children, whether obese children differ
from non-obese with regard to metabolic adaptation
to changes in dietary carbohydrate and fat content,
and whether exercise will improve glucose metabolism
and insulin sensitivity in obese children. Dr Sunehag
is also involved in studies of glucose metabolism in
lactating women and in children with type 1 diabetes.
Deborah
I. Thompson, Ph.D.
Dr.
Thompson is interested in children's problem solving
to overcome barriers to physical activity and in the
design, development, and evaluation of eHealth programs.
Dr. Thompson is studying the use of Dual Code Theory
and how to best design interactive multi media programs
to promote health behavior change, as well as the impact
of monetary incentives on log-on rates to an eHealth
program promoting diet and physical activity change.
She also coordinates qualitative research for a large,
multi-site study to prevent type 2 diabetes among middle
school youth. Qiang Tong, Ph.D.
The study of
adipose tissue development may reveal clues about the
molecular mechanisms of metabolic diseases, such as
type 2 diabetes and cardiovascular disease. Dr. Tong
has established the mammalian GATA transcription factors
as molecular gatekeepers in the early stages of adipogenesis.
He demonstrated that both GATA-2 and GATA-3 transcription
factors are negative regulators of adipocyte differentiation.
This effect is mediated through direct suppression
of the promoters of adipogenic factors PPARg and C/EBPa
by GATA factors and protein-protein interactions between
GATA and C/EBPa or C/EBPb. Currently he is investigating
the regulation of GATA factors at the protein level,
with the goal of characterizing the identity and dynamics
of the GATA protein complexes during adipogenesis,
and the role of GATA in the lineage determination of
adipogenic progenitor cells. He also plans to identify
new regulators of adipogenesis and to develop mouse
models to study the roles of these genes in obesity.
Ignatia B. Van den Veyver,
M.D.
The neurodevelopmental disorder Rett
syndrome is caused by mutations in a gene on the X
chromosome, MECP2 .
This gene encodes methyl-CpG-binding protein 2, thought
to be a transcriptional repressor that binds to methylated
CpGs in DNA. Based on this, we propose the more general
hypothesis that DNA methylation is important for regulation
of gene expression during development, especially of
the brain. There is evidence that DNA methylation can
be influenced by methyl-donor enriched diets, containing
substances such as folic acid and betaine. We are investigating
in animal and cell culture models whether this treatment
can alter DNA methylation and gene expression in the
brain. 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 prenatally-onset
disorders and birth defects, such as neural tube defects
or for the fetal origin of adult-onset disorders.
William
W. Wong, Ph.D.
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 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
currently investigating the safety, efficacy, and optimal
dosage of soy isoflavones to prevent osteoporosis in
postmenopausal women and the effects of soy isoflavones
on nitric oxide production and blood pressure in postmenopausal
women with high-normal blood pressure.
Issa
F. Zakeri, Ph.D.
Dr. Zakeri
is interested in Nutrimetrics, 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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