Department of Pediatrics
Ph.D., Univeristy of Washington
Phone: (631) 444-7646
The ability of neural stimuli to regulate gene expression provides one
means of integrating the many types of information typically received by
a single neuron. Often the production of mRNA serves as the first step
in gene regulation. Frequently transcriptional regulatory sites on DNA
function as focal points to coordinate a gene's response to these
influences. Currently I investigate regulation of the gene encoding
phenylethanolamine N-methyltransferase (PNMT), the final enzyme in the
catecholamine biosynthetic pathway. The objective of our research is to
learn how neural stimuli, primarily neurotransmitters, can regulate the
expression of other neural genes, using transcription of the PNMT gene
as a model system. Physiologically, it has been established that
catecholamine enzymes are stimulated by "chronic stress", a general term
encompassing the ability of neurotransmitters and/or neural impulses to
induce PNMT expression transynaptically. We have determined that
cholinergic stimuli (e.g. acetylcholine) induce production of PNMT mRNA
through two separate receptor systems, i.e. nicotinic and muscarinic,
which involve distinct second messenger intermediates. Knowing that
neural influences affect transcription of the PNMT gene has served as
the basis for mapping the cis-active elements on this gene that convey
responsiveness to nicotinic, muscarinic, and depolarizing stimuli. Our
future research directions involve identification of those nuclear
proteins that interact with neurally responsive sites on the PNMT gene.
These studies should contribute significantly toward understanding the
molecular basis of transmitter production and regulation in the central
and peripheral nervous systems.
Additionally, we explore expression profiles of developmental-specific transcription factors in neuronal tumors and cell lines. Medulloblastoma and neuroblastoma tissues serve as CNS and PNS models of altered gene expression that may prove instrumental for understanding transformaion to the malignant neuronal phenotype.
- Laboratory Personnel
- Evinger, M.J., Cikos, S., Nuafor-Anene,V., Powers, J.F., and Tischler, A.S. (2002) Hypoxia activates multiple transcriptional pathways in mouse pheochromacytoma cells. Ann. New York Acad. Sci. (O'Connor, D.T. and Eiden, L., eds) 971. In Press.
- Powers, J.F., Evinger, M.J., Tsokas, P., Bedri, S., Alroy, J.F., Shahsavi, M., and Tischler, A.S. (2000) Pheochromatocytoma cell lines from neurofibromatosis knock out mice. Cell and Tissue Res 302:309-320.
- Lee, Y-S. E., Raia, G., Tonshoff, C., and Evinger, M.J. (1999) Neural regulation of phenylethanolamine N-methyltransferase (PNMT) gene expression in bovine chromaffin cells differs from other catecholamine biosynthetic enzyme genes. J. Molecular Neuroscience 12: 53-68.
- Evinger, M.J. (1998) Determinants of phenylethanolamine N-methyltransferase expression. Adv. Pharmacol. 42: 73-76.
- Tonshoff, C., Hemmick, L., and Evinger, M.J. (1997) Pituitary adenylate cyclase activating polypeptide (PACAP) regulates expression of catecholamine biosynthetic enzyme genes in bovine adrenal chromaffin cells. J. Molecular Neuroscience, 9: 127-140.
- Evinger, M.J., Ernsberger, P., Regunathan, S., Joh, T.H., and Reis, D.J. (1994) A single transmitter regulates gene expression through two separate mechanisms: Cholinergic regulation of phenylethanolamine N-methyltransferase mRNA via nicotinic and muscarinic pathways. J. Neurosci. 14: 2106-2116.