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My laboratory is interested in developmental, nutritional, gastrointestinal and environmental regulation of gene expression.
We chose the rat small intestine as model because it provides an excellent example of how developmental timing mechanisms are exquisitely programmed to match changes in function. During birth, placental nutrition ceases and enteral nutrition begins. The small intestine acquires many enzymes and transporters before birth to digest then absorb nutrients from milk. During weaning, the small intestine synthesizes different types or different numbers of enzymes and transporters to match expected changes in luminal substrate concentrations arising from an increasing variety of food. We are interested in identifying the signals that lead to adaptive changes in transporter expression. We use micro-array hybridization to determine the pathways of substrate:transporter signal transduction. Once a candidate signaling molecule is identified, it is then stimulated or inhibited to determine its role in regulating transporter gene expression during development. This project is relevant to premature babies born with underdeveloped intestines: if late onset transporters can be induced to appear earlier during development, it would allow feeding of critical nutrients that would otherwise cause complications in the developing intestine.
Conventional indicators of malnutrition
are clinical: excessive changes in body weight and abnormal plasma profiles of
nutrients are among many. High throughput genetic screening methods now allow
investigators to identify factors that change acutely in response to malnutrition,
well before more serious symptoms are detected. We are using a fish model and
the techniques of microarray, subtractive hybridization and RT-PCR to identify
genes whose mRNA abundance changes markedly in response to dietary restriction
or excess of a nutrient. The validity of these potential predictors of malnutrition
is compared with that of conventional indicators. Their importance is evaluated
by altering their function using pharmacological agents, to determine how alterations
of their expression lead to clinical symptoms.