The
NIH Center for
Structural and Functional Neuroscience (CSFN)
The NIH Center for Structural
and Functional Neuroscience (CSFN) was established at The University
of Montana as a Center of Biomedical Research Excellence (COBRE) through
the Institutional Development Award (IdeA) program of the National Center
for Research Resources (NCRR). The research mission of the Center is
to utilize approaches at the interface of chemistry, biochemistry, pharmacology,
toxicology and molecular biology to advance our understanding of protein
structure and function in the central nervous system, particularly as
related to signal transduction, transport, development and pathogenesis.
The Center is also intended to serve as a core around which to develop
infrastructure that benefits a much broader range of basic, clinical
and translational biomedical research efforts in Montana. Multidisciplinary
by design, Center investigators hold faculty positions in the Department
of Pharmaceutical Sciences, the Department of Chemistry and the Division
of Biological Sciences at the University of Montana. In addition to
the Missoula campus, Center investigators are also located at the McLaughlin
Research Institute in Great Falls and at Montana State University.
Center for Structural and Functional
Neuroscience
Basic Research Investigator
Bios
Richard
J. Bridges, Director, Center for Structural and Functional Neuroscience
Professor, Department of Pharmaceutical Sciences, The University of
Montana
After completing undergraduate work in Biochemistry at the University
of California at Davis, Richard Bridges received a Ph.D. in Biochemistry
from Cornell Medical College in 1984. Following postdoctoral and faculty
positions at the University of California at Irvine, he moved to the
University of Montana as an Associate Professor in 1993. He was promoted
to Professor in 1998. In 2000, Bridges became the Director of an NIH
Center for Biomedical Research Excellence in Structural and Functional
Neuroscience at the University of Montana. Bridges serves on the Board
of Directors of the Montana Neuroscience Institute Foundation.
Interests of the Bridges
Laboratory Group
Research in the group focuses primarily on the neurochemistry of the
amino acid glutamate. The balance between the physiological and pathological
actions of glutamate is believed to be maintained, in part, by a family
of glutamate transporter proteins. Work in the Bridges laboratory is
aimed at understanding how these transport proteins work, how the systems
normally function to regulate glutamate levels, and whether or not compromised
function may contribute to brain pathology in neurological disorders
like stroke, epilepsy, spinal cord injury, ALS or Alzheimer's disease.
Experimental approaches used by the research group range from the organic
synthesis and molecular modeling of novel glutamate analogues to the
utilization of selective inhibitors and substrates as probes of transporter
function and dysfunction. A particular emphasis is placed on delineating
the structure activity relationships that appear to be unique to each
of known transporter systems.
Charles
M. Thompson, Co-Director, NSF-EPSCoR program
Professor, Department of Pharmaceutical Sciences, The University of
Montana
After completing undergraduate work in Chemistry at Rutgers University,
Charles Thompson received M.S. (1980) and Ph.D. (1982) degrees in Chemistry
from The University of California, Riverside. Following postdoctoral
appointments at Harvard University (192-1983) and The University of
California, Berkeley (1983-1985) he held a faculty position in Chemistry
at Loyola University of Chicago (1985-1994). He moved to the University
of Montana as an Associate Professor in 1994 and was promoted to Professor
in 1996. In 2000, he became the co-Director of the University of Montana
National Science Foundation (NSF) Experimental program to Stimulate
Competitive Research (EPSCoR) at the University of Montana.
Interests of the Thompson
Laboratory Group
Research in the group uses a combination of [bio]chemical, cellular
and spectroscopic approaches to solve problems in neuroscience, particularly
the neurotransmitter systems, glutamate acetylcholine and glutamate.
Three principal approaches a currently underway include: 1) Design and
synthesis of pharmacologically active compounds to probe, regulate and
inhibit neurotransmitter systems; 2) Computer-aided modeling to design,
simulate and visualize pharmacophore models for receptors, enzymes and
transporters; 3) Application of proteomics to neurotransmitter systems;
and, 4) Development and applications of custom-tailored antibodies for
immunologic detection in neurotransmitter systems.
David
J. Poulsen
Research Assistant Professor, Department of Pharmaceutical Sciences,
The University of Montana
After completing a Bachelors degree in Microbiology at Brigham Young
University, Poulsen obtained his Masters and Ph.D. degrees in Molecular
Virology from the University of Delaware. Following the completion of
his doctoral degree, he trained at the National Institutes of Health
as an Intramural Training Research Award (ITRA) fellow in the Laboratory
of Persistent Viral Diseases (National Institute of Allergy and Infectious
Disease, Rocky Mountain Laboratories). Following his training at the
NIH, Dr. Poulsen served a second post-doctoral fellowship in the CNS
Gene Therapy Center at Thomas Jefferson University in Philadelphia,
PA. In 2001, Poulsen joined the Montana Neuroscience Institute as a
Research Assistant Professor in the Department of Pharmaceutical Sciences
at the University of Montana and as a Translational Research Scientist
with St. Patrick Hospital and Health Sciences Center.
Interests of the Poulsen
Laboratory
Research in the group is ultimately directed toward the development
of gene therapy based applications for the treatment of neurological
disorders such as epilepsy, Amyotrophic Lateral Sclerosis (ALS), chronic
pain, as well as spinal cord injury and regeneration. In addition, the
Poulsen laboratory is also developing genetic therapies for the treatment
of hearing loss through the regeneration of hair cells within the inner
ear. The primary gene delivery vehicle used in the development of these
treatment strategies is the Adeno-Associated Virus (AAV). AAV is the
delivery vector for a number of reasons. It can infect multiple cell
types including terminally differentiated neuron and is nonpathogenic.
Although about 85% of the world population is infected with AAV by 10
years of age, it has never been associated with pathology or disease.
Experimental approaches used in the development of gene therapy applications
in the Poulsen laboratory range from standard molecular cloning and
gene expression to the stereotactic delivery of recombinant AAV to the
brain and spinal cord.
John
M. Gerdes
Associate Professor, Department of Chemistry, The University of Montana
After completing undergraduate work in Chemistry at Colorado State University
during 1978, Gerdes received a Ph.D. in Chemistry from the University
of California at Riverside (1982). Following a postdoctoral position
at U. C. Berkeley, he joined Lawrence Berkeley National Laboratory (LBNL)
as a staff scientist in 1986. During 1991 he began his industrial experience,
working for Zenenca, Ltd., which was followed by a faculty post within
the Department of Chemistry at Central Washington University (1995).
He was promoted to full professor in 2001 and subsequently joined the
CFSN and the Department of Chemistry at The University of Montana during
September, 2001.
Interests of the Gerdes Laboratory
Group
Our research encompasses a full spectrum of medicinal chemistry studies
of the serotonin (5-HT) system and other integrated complexes. Many
of the investigations are focused on pre- and post-synaptic ligands
and the structured-function of various 5-HT receptors (transporter,
5-HT1A, 5-HT2A-C). Our efforts involve small molecule superposition-consensus
pharmacophore model generation through innovative computational means.
The models serve to drive various de novo drug design venues and synthetic
initiatives, including the fabrication of novel therapeutic agents,
diagnostic probes and biochemical reagents. Of particular interest are
those investigations that are carried out with collaborators at the
Center for Functional Imaging, LBNL, where select drugs from our laboratory
are evaluated as functional brain imaging agents in living brain.
Diana
I. Lurie
Associate Professor, Department of Pharmaceutical Sciences, University
of Montana
After completing undergraduate work in Biopsychology at Wesleyan University
in Middletown, Connecticut, Lurie received a Ph.D. in Neuroscience from
The University of Pennsylvania in 1989. Following a postdoctoral fellowship
at the University of Washington, she moved to the University of Montana
as an Assistant Professor in 1995. She was promoted to Associate Professor
in 2000.
Interests of the Lurie Laboratory
Group
Research in the group focuses on the glial response to central nervous
system (CNS) injury and disease. Specifically, Lurie and her co-workers
are interested in cellular cascades that control the proliferation and
migration of glial cells following damage, as well as those processes
that regulate both the production of, and the glial response to, various
growth factors. Recent work has centered on elucidating the role that
tyrosine phosphorylation plays in these signal transduction events during
CNS injury, including stroke. The Lurie laboratory has three major focus
areas: 1) the response of the brain to stroke injury, 2) the response
of the auditory brainstem to loss of activity in the ear, and 3) the
effect of lead exposure on the developing auditory system.
Keith
K. Parker
Associate Professor, Department of Pharmaceutical Sciences,
University of Montana
After completing undergraduate work in Psychology at Montana State University,
Parker received a Ph.D. in Pharmacology and Toxicology from the University
of California, San Francisco in 1977. Following postdoctoral positions
at the University of Colorado Health Sciences Center in Denver and the
University of Denver, he moved to Western Montana College in 1981 where
he remained until 1993. At that time he assumed his current position
at the University of Montana.
Interests of the Parker Laboratory
Group
The group has a long-standing applied interest in understanding headache,
and particularly in developing better anti-migraine headache drugs.
Because the neurotransmitter serotonin (5HT) has been implicated in
the pathology of migraine headache, the group is focused on receptors
that bind to serotonin. Because serotonin mechanisms are also associated
with depression, anxiety, obsessive-compulsive disorders, and panic
disorder, this work has additional applications. Much of the work in
the Parker laboratory is focused on the interface between the 5HT1a
receptor, and the signal transducing molecule, G protein. Our recent
work has emphasized small peptides, which we have synthesized based
upon the sequences of intracellular loops 2 and 3. We are using these
peptides as molecular tools for analyzing the specific structural requirements
of the receptor-G protein system. These peptides may eventually be prototypes
for new drug structures. A secondary focus of the lab is the analysis
of natural product drugs for anti-migraine treatments.
C.
Sean Esslinger
Research Assistant Professor, Department of Pharmaceutical Sciences
University of Montana
After completing undergraduate work in Chemistry at New Mexico State
University, Esslinger received a Ph.D. in Chemistry from Colorado State
University in 1992. Following a postdoctoral position at the University
of California at Irvine, he became the first NIH postdoctoral fellow
in the history of the University of Montana in 1997. In 2000, Esslinger
joined the NIH Center for Biomedical Research Excellence in Structural
and Functional Neuroscience at the University of Montana. He is a research
assistant professor in the Department of Pharmaceutical Sciences, and
is affiliated with the Department of Chemistry.
Interests of the Esslinger
Laboratory Group
Research in the group focuses
primarily on the neurochemistry of the amino acid glutamate, the major
excitatory signaling molecule in central nervous system (CNS), and the
glutamate metabolic precursor glutamine. This research is focused on
delineating the process of membrane translocation within neurons and
glia by these amino acids, and how these processes contribute to both
normal and diseased brain function.. Through the use of asymmmetric
syntheses of amino acid analogues with subsequent molecular modeling
of the bioassay data, these interactions are analyzed to determine the
important and possibly selective interactions occurring between the
ligand and the various transport proteins. Testing of these novel synthetic
analogues occurs in the Esslinger laboratory as well as the Bridges
and Thompson laboratories.