Jane E. Cavanaugh, Ph.D.
Assistant Professor of Pharmacology

455 Mellon Hall
T 412.396.6358
E cavanaughj@duq.edu

B.A. -- Franklin & Marshall
Ph.D. -- Pennsylvania State College of Medicine

• L. Liu, J.E. Cavanaugh, Y. Wang, H. Sakagami, Z. Moa, Z. Xia. ERK activation of MEF2-mediated gene expression plays a critical role in BDNF-mediated survival of developing but not mature cortical neurons. Proc. Nat. Acad. Sci., 100(14): 8532-8537, 2003. these authors contributed equally
• J.E. Cavanaugh. Role of extracellular signal regulated kinase 5 in neuronal survival. Eur. J. Biochem., 271(11): 2056-2059, 2004.
• J.E. Cavanaugh, J.D. Jaumotte, J.M. Lakoski, M.J. Zigmond. Neuroprotective role of ERK1/2 and ERK5 in dopaminergic cells under basal conditions and in repsonse to oxidative stress. J. Neurosci. Res.,  84(6): 1367-1375, 2006.
• E. Lin, J.E. Cavanaugh, R.K. Leak, R.G. Perez, M.J. Zigmond. Effect of 6-hydroxydopamine on ERK activation in a dopaminergic cell line: Relation to cell survival. Neuroscience, Submitted for publication.

• "The Role of ERK1/2 in GDNF-Mediated Neuroprotection of Midbrain Dopaminergic Neurons, " 37th Winter Conference on Brain Research, Copper Mountain, CO, January 2004.
• "Neurotoxin-induced DA Neurodegeneration: Assessment of Mobility and Intracellular Signaling with Aging," Claude D. Pepper Center for Aging, University of Pittsburgh, Pittsburgh, PA, April 2006.
• "Behavioral and Immunohistochemical Assessment of Dopaminergic Neurodegeneration in an MPTP Model of Parkinson’s Disease," Departments of Biology and Psychology, Franklin and Marshall College, Lancaster, PA, April 2006.
• "Studies of MAP Kinases in Aging and Oxidative Stress," Department of Neurology, University of Virginia, Charlottesville, VA, May 2006.

My scholarly interests are focused on the regulation of neuronal survival and apoptosis which occurs during normal and diseased aging. Dopamine (DA) neurons of the CNS play an essential role in movement. DA neurons are lost throughout life, a process that is attenuated by the actions of endogenous neurotrophic factors (NT) and exacerbated by environmental toxins. Initially, the loss of DA cells appears to have few if any consequences due to the compensatory capacity of the brain. However, with increasing age, compensations decline, and it is likely that the combination of DA cell loss and reduced compensation plays a role in age-related functional impairments. Parkinson's disease (PD), which is accompanied by a dramatic increase in DA cell loss, may well represent an extreme case of the intersection of environmental toxicity and age-related reductions in compensatory processes. One mechanism by which cell death is blocked in neurons is the activation of the extracellular signal-regulated kinase (ERK) pathways which are members of the mitogen-activated protein kinase (MAPK) family. Neurotrophin-mediated activation of the ERK1/2 signaling cascades is important for neuroprotection from a variety of toxic insults. Interestingly, the expression and activation of the ERK1/2 signaling pathways decrease with normal aging, and thereby may contribute to an age-related decrease in neuronal survival. In 1995, ERK5, a new member of the MAPK family, was discovered. Since that time, ERK5 has received relatively little attention. However, like ERK1/2, ERK5 has been implicated in neuroprotection by studies that I performed while a postdoctoral fellow, as well as a few other studies. Recently, we have also shown that ERK5 expression in the brain declines with age. Many of the studies that implicate ERK1/2 in neuroprotection have relied on pharmacological inhibitors of ERK1/2 activation that also inhibit the ERK5 pathway. Thus, some of the functions hitherto attributed solely to ERK1/2 may be regulated by ERK5 exclusively or in conjunction with ERK1/2. Currently I am studying the role of ERK5 together with ERK1/2 in neuronal survival with aging using a specific cell type (dopamine neurons) exposed to a selective toxin (6-hydroxydopamine; 6-OHDA) that produces a specific insult (oxidative stress).
I am concurrently investigating the role of ERK pathways in neuronal survival with aging under normal conditions and with chronic exposure to a selective toxin (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine, MPTP) that mimics the action of many environmental contaminants in dopamine neurons. MPTP produces a depletion of dopamine neurons in the substantia nigra, dopamine terminals in the striatum and results in a loss of motor function as assessed by various behavioral analyses.
Although studies of the neuroprotective role of MAPKs have previously been reported, the combination of aging, chronic exposure to a neurotoxin, and a focus on ERK pathways is unique and should advance our understanding of regulation of neuronal vulnerability during normal aging and in neurodegenerative diseases. It should also provide insights in the development of new therapeutic agents for age-related motor impairments.

My professional interests are focused on neuroscience and the neurobiology of aging. To maintain visibility among neuroscientists, I am currently an active member in the Society for Neuroscience and participate in their annual meetings. I am also involved in the Winter Conference on Brain Research and have presented scientific talks at this meeting to the other neuroscientists and to local grade schools. I am also actively involved in the Faculty for Undergraduate Neuroscience organization. This organization provides valuable educational resources to use in the teaching of undergraduate and graduate students. Furthermore, it gives me the opportunity to interact with undergraduate students around the world at the annual Society for Neuroscience meeting.  Finally, I am involved in outreach programs targeted to the Pittsburgh public schools. I coauthored a grant to the Society for Neuroscience for a Scientist Teacher Educational Partnership for a day of “teaching the teachers.” Through this program, I was paired with a middle-school teacher in the Pittsburgh area and have visited his school to teach the students about the effects of drugs on the brain.