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Associate Professor, Pharmacological Sciences
talmage@pharm.stonybrook.edu
I have a long standing interest in how cells respond to their environment –
mechanistically, a process commonly known as signal transduction. The current focus of our studies is on how
one pair of molecules, Nrg1 and ErbB4, interact to regulate synapse formation
and maintenance. The Nrg1 gene encodes a
family of ~20 different proteins that serve as ligands for members of the ErbB
family of receptor tyrosine kinases. These proteins have long been recognized
as playing important roles during vertebrate development, and inappropriate
Nrg1 – ErbB signaling plays key roles in such diverse diseases as breast cancer
and schizophrenia.
The Type III subfamily of Nrg1 isoforms are expressed exclusively in neurons, and are
“shipped” to both axonal and dendritic processes. We have demonstrated that this subfamily of
Nrg1 proteins function both as ligands for ErbB receptors and as receptors;
i.e. they participate in bi-directional, juxtacrine signaling that mediates
interactions between Type III Nrg1
expressing neurons and ErbB expressing neurons or glia. These interactions are
required for myelination of peripheral nerves, survival of motor and sensory
neurons and aspects of plasticity at central synapses. Currently, in close collaboration with the
laboratory of Dr. Lorna Role, we are attempting to understand the function of
Type III Nrg1 in the development
of the nociceptive population of sensory neurons, and in the establishment of
cholinergic modulation of cortical-limbic circuits. In addition we are
dissecting the relative contribution of Type III
Nrg1 “forward” vs. “reverse” signaling in these processes.
Selected Publications
Matsumoto, Y., Kim, K., and Bogenhagen D.F. (1994). Proliferating cell nuclear antigen (PCNA)-dependent abasic site repair in Xenopus laevis oocytes: an alternative pathway of base excision repair. Mol. Cell. Biol. 14. 6187-6197
Chen,
Y-J, Role, L.W. and Talmage, D.A. Neuregulin and Schizophrenia. in Handbook of
Neurochemistry and Molecular Neurobiology, in press.
Talmage,
D.A. Mechanisms of Neuregulin 1 signaling, in Growth factors and psychiatric
disorders, Novartis Found. Symp. 289, p 74-86, 2007.
Role, L.W. and Talmage,
D.A. Neurobiology: new order for thought
disorders. Nature 448:263-5,
2007.
Berman,
J. Talmage, D.A. and Role, L.W. Cholinergic circuits and signaling in the
pathophysiology of schizophrenia. Int.
Rev Neurobiology 78: 193 – 223, 2007.
López-Bendito,
G., Cautinat, A., Sánchez, J.A., Bielle, F., Flames, N., Garratt, A.N.,
Talmage, D.A., Role, L.W., Charnay, P.
Marín, O. and Garel, S. 125, 127-142, 2006.
Jo, YH, Chen, Y.J.,
Chua, S., Talmage, D.A. and Role, L.W. Leptin regulates endocannabinoid
signaling in an appetite-related neural circuit. Neuron 48:1055-1066, 2005.
Talmage, D.A. and Role, L.W. Multiple personalities of neuregulin gene family
members J. Comp. Neurology,
472:134-139, 2004.
Tighe, A.P. and Talmage, D.A. Retinoids arrest breast cancer cell proliferation: Retinoic acid
selectively reduces the extent and duration of receptor tyrosine kinase
signaling. Expt. Cell Research
301:147-157, 2004.
Bao, J., Wolpowitz, D., Role, L.W. and Talmage,
D.A. Back-signaling by the Nrg-1
intracellular domain. J. Cell Biology 161:1133-1141, 2003.
Jo, Y.H., Talmage, D.A. and Role, L.W. Nicotinic
receptor-mediated effects on appetite and food intake. J. Neurobiology
53:618-632, 2002.
Cho, Y. and Talmage, D.A. Protein kinase Ca
expression confers retinoic acid sensitivity in MDA-MB-231
human breast cancer cells. Expt. Cell Research, 269:97-108, 2001.
Wolpowitz,
D., Mason, T.B.A., Mendelsohn, M., Talmage, D.A. and Role, L.W. Requirement for
cysteine-rich domain isoforms of the Neuregulin-1 gene in synapse
formation. Neuron 25:79-91, 2000.
Bao,
J.-X., Talmage, D.A., Role, L.W. and Gautier, J. Regulation of neurogenesis by
interactions between HEN1 and neuronal LMO proteins. Development 127:425-435,
2000.
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