Developmental Pharmacology and
Toxicology Laboratory
Research in this laboratory is aimed toward understanding the interaction of drugs, hormones and environmental factors with the developing organism, with particular emphasis on the fetal and neonatal nervous system. The role of biochemical factors mediating development of nerve cells and other types of tissue is a major thrust, since they influence the subsequent structural and physiological status of critical organ systems. Of necessity, students and fellows typically are trained in biochemical/molecular, anatomical, behavioral and physiological techniques, since a multidisciplinary approach must be used in such studies.
Ongoing projects comprise five areas:
1- Mechanisms regulating development of synapses: role of endocrine and other trophic factors; intracellular messengers in developing cells; control of target organ differentiation by neural input.
2- Adverse effects of exogenous agents on development, with an emphasis on identification of mechanisms by which behavioral or physiological damage occurs; drugs of abuse (especially nicotine), hormonal imbalances, environmental contaminants (especially pesticides), food additives, intrauterine growth retardation, fetal and neonatal hypoxia.
3- Control of fetal and neonatal cardiovascular and respiratory function by the immature nervous system; normal physiological mechanisms, responses to stress, factors mediating the transition from fetal to neonatal function, reactivity during delivery, Sudden Infant Death Syndrome.
4- Molecular mechanisms in human brain dysfunction in the elderly; Alzheimer's Disease and Depression.
5- Breast cancer cell growth regulation. Role of hormone and neurotransmitter receptors converging on common cell signaling mechanisms, and targeting of these receptors for cancer therapeutics.
Trainees receiving their degrees in this laboratory have performed research on: effects of fetal exposure to antihypertensive drugs and opiates on nervous system development; biochemical and physiological characterization of synaptic development in the heart; endocrine regulation of nerve development; trophic control of development of brain cells by endogenous and exogenous biogenic amines; nervous system participation in the response of fetus and neonate to stress and hypoxia; control of neurotransmitter receptor expression and receptor transduction systems during development; animal models of Sudden Infant Death Syndrome; and control of protooncogene nuclear transcription factors during development and carcinogenesis. In keeping with the diverse interests of the research group, current funding comes from the National Institute of Child Health and Human Development, the National Institute of Mental Health, the Department of Defense, and private foundations.
New directions within the laboratory are concentrating on neural and hormonal control of cell differentiation, growth control and gene expression:
1- Control of gene expression of neurotransmitter receptor proteins and second messenger cell signaling components. Role of b-adrenergic, thyroid and steroid receptors in cell growth regulation during development and in cancer cell lines.
2- Glucocorticoid receptor expression and regulation by developing cells; role of glucocorticoid receptors as a target for developmental abnormalities in cell differentiation and physiological function.
3- Neurotransmitter control of cell differentiation in the central nervous system; role of transient receptor expression and transduction in timing of replication — differentiation switchover; molecular mechanisms underlying control of fetal oncogenes.
4- Animal models of elderly depression. Molecular biology and pharmacology of serotonin transporter molecules in aging brain. Control of transporter expression by glucocorticoids.
Applicants should submit a cover letter indicating area of interest, curriculum vitae and the names of three references to:
Dr. Theodore A. Slotkin
Dept. of Pharmacology and Cancer Biology
Box 3813
Duke Medical Center
Durham, NC 27710
see Dr. Slotkin's CV