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Peter D Holohan, Ph.D.
Professor, Pharmacology
3157 Weiskotten Hall
Upstate Medical University
750 East Adams Street
Syracuse, NY 13210
(315) 464-7960
| Education and Clinical Training
Ph.D.: 1973, Syracuse University
Research Program and Department Affiliations
Pharmacology
Research Interests Drug secretion
Research Abstract
The primary interest of the laboratory
is to understand in molecular terms an inherited neurodegenerative disease
that we have recently described, Familial Encephalopathy
with Neuroserpin Inclusion Bodies (FENIB). The disease
is caused by point mutations in the gene encoding a neuron-specific serine
protease inhibitor, neuroserpin. The mutations translate into proteins
that are prone to self-polymerization and intracellular aggregation. Different
mutations result in different ages of onset, from adolescence to adulthood,
and in different degrees of severity; however, all present clinically with
epilepsy and progressive dementia. Our studies utilize both in
vivo (i.e., transgenic animals) and in vitro
(i.e., cell culture) models. The objectives are to describe why the inappropriate
cellular processing of neuroserpin leads to disruption of synaptic structure
and function, why this presents clinically as a seizure disorder, and why
unregulated electrical activity causes loss of cognitive function. The
long-term goal is to suggest pharmacotherapeutic interventions that could
block the pathogenic cascade, and thereby either restore normal function
or at the very least, ameliorate further deterioration.
Selected References
Davis RL, Holohan PD, Shrimpton AE, Tatum AH, Daucher J, Collins GH,
Todd R, Bradshaw C, Kent P, Feiglin D, Rosenbaum A, Yerby MS, Shaw CM,
Lacbawan F, Lawrence DA. Familial encephalopathy with neuroserpin inclusion
bodies. Am J Pathol. 1999 Dec;155(6):1901-13.
Davis RL, Shrimpton AE, Holohan PD, Bradshaw C, Feiglin D, Collins GH,
Sonderegger P, Kinter J, Becker LM, Lacbawan F, Krasnewich D, Muenke M,
Lawrence DA, Yerby MS, Shaw CM, Gooptu B, Elliott PR, Finch JT, Carrell
RW, Lomas DA. Familial dementia caused by polymerization of mutant neuroserpin.
Nature. 1999 Sep 23;401(6751):376-9.
Publications - link to PubMed
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This profile was last updated on 02/18/2008
A short link is available for this profile:
http://www.upstate.edu/pharm/faculty.php?ID=holohanp
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