James F. Padbury - Pediatrics Faculty Profile

James F. Padbury
Pediatrician-in-Chief • Professor, The Warren Alpert Medical School of Brown University
MD, UCLA, Los Angeles, 1973
401-274-1122, x1205
James_Padbury@Brown.edu

Dr. Padbury’s team’s work is in the area of developmental biology and molecular pharmacology. They are interested in the biology of adrenergic receptors and biogenic amine transporters during development. Maturation of the hypothalamic pituitary and adrenal axes is one of the central events during intrauterine development of all mammalian species. Through some well characterized and some unclear mechanisms, the expression of important genes involved in regulation of cell function and cell and organ structure are induced. The team has identified the beta 1-adrenergic receptor (beta 1AR) as a gene whose expression is induced in postnatal and adult animals by glucocorticoids and thyroid hormones but not in fetal animals. The mechanism for this switch in transcriptional activation was not known. They have cloned and are characterizing the promoter of this receptor. They have also identified a novel glucocorticoid regulatory unit which contains a consensus sequence for bHLH transcription factors and may couple beta 1AR transactivation to regulation of cardiac cell cycle via the myc/max family of proteins. Observation is important as activation of myocardial beta 1-adrenergic receptors is the predominant mechanism for minute to minute regulation of cardiac activity and its activity and expression are tightly regulated. Dysregulation of the beta 1-adrenergic receptor underlies a number of pathobiological conditions including the transition from fetal to neonatal life and cardiac hypertrophy and congestive heart failure.

The team also interested in the developmental expression and regulation of biogenic amine transporters, and they have identified the placenta as an unusual site of these "neuronal proteins," responsible for the reuptake of neurotransmitters like norepinephrine, epinephrine, dopamine and serotonin. The placenta is a unique non-neuronal site of neurotransmitter transport. They have cloned homologs of the serotonin and norepinephrine transporters from the placenta. They have also cloned the 5' flanking sequence of the norepinephrine transporter gene and are doing studies on differential regulation of this gene in neuronal and placental cells. These studies are important to the mechanisms of early embryogenesis, placentation and later intrauterine regulation of fetal growth. The researchers believe they are also relevant to the pathobiology of disorders of placental function like preeclampsia and to the molecular mechanisms for the unique vulnerability of the fetus to uptake inhibitors like cocaine.

Selected Publications
• Tseng YT, Yano N, Rojan A, Stabila JP, McGonnigal BG, Ianus V, Wadhawan R, Padbury JF. Ontogeny of Phosphoinositide 3-Kinase (PI3K) Signaling in Developing Heart: Effect of Acute {beta}-Adrenergic Stimulation. Am J Physiol Heart Circ Physiol. 2005 Jul 8; [Epub ahead of print]
• Lum LG, Padbury JF, Davol PA, Lee RJ. Virtual reality of stem cell transplantation to repair injured myocardium. J Cell Biochem. 2005 95:869-74.
• Hleb M, Murphy S, Wagner EF, Hanna NN, Sharma N, Park J, Li XC, Strom TB, Padbury JF, Tseng YT, Sharma S. Evidence for cyclin D3 as a novel target of rapamycin in human T lymphocytes. J Biol Chem. 2004 279:31948-55.
• Padbury JF, Diah SK, McGonnigal B, Miller C, Fugere C, Kuzniar M, Thompson NL: Transcriptional regulation of the LAT-1/CD98 light chain. Biochim Biophys Acta 318, 535-540, 2004.