Wright State University announced today that is has received a prestigious
Program Project Grant (PPG) from the National Institute of Neurological
Disorders and Stroke (NINDS). The $4.8 million grant is the first Program
Project Grant Wright State University has received. Five university scientists
will use the grant to further their research into why full recovery is
not always achieved after damaged nerves have regenerated.
“These grants are extremely competitive, and this award underscores
the high caliber of neuroscience research being conducted at Wright State,” said
David R. Hopkins, president of Wright State. “In this research
arena we are successfully competing at a national level. We are extremely
proud that Wright State has taken a leadership role by bringing this
Program Project Grant to the region.”
Program Project Grants are designed to “encourage multidisciplinary
research approaches to a diverse array of nervous system disorders,” according
to NINDS, one of the 27 institutes and centers that comprise the National
Institutes of Health, and the guidelines require at least three interrelated
projects that contribute to the program objective. Five collaborative
projects, each led by a Wright State NIH-funded investigator, will work
together to better understand the recovery—or lack of it—from
neurotrauma.
The team of Wright State investigators—Drs. Francisco Alvarez,
Timothy Cope, Kathrin Engisch, Robert Fyffe and Mark Rich—are accomplished
researchers in fields covering developmental biology, synaptic function
and sensorimotor behavior of the spinal cord and peripheral nervous system.
The diversity of their analytical viewpoints will, through this grant,
create a synergy of research information focused on a common interest.
(see sidebar on the five projects)
Above: Researchers (left to right) Robert
E.W. Fyffe, Ph.D., Timothy Cope, Ph.D., Francisco Alvarez, Ph.D., Kathrin
Engisch, Ph.D., and Mark Rich, M.D., Ph.D.
Download a High-Resolution image suitable for printing by selecting the
photo above.
When the Connections No Longer Work: After Nerves Regenerate
Our wired communication system sends and receives electrical impulses
from the central nervous system (CNS) through a highly specialized peripheral
nervous system (PNS), which transmits sensory information and controls
movement. The PNS relays messages from the body to the brain and regulates
internal processes. When the PNS is damaged, nerve activity may be blocked,
interrupted or completely disrupted, depending on the severity of the
injury.
Damage to the PNS, peripheral neuropathy, includes more than 100 classifications,
each unique in its presenting symptoms, based upon the type of nerves damaged—motor,
sensory, or autonomic, or a combination of these. The most common cause of peripheral
neuropathy is trauma. But, chemotherapy and a wide range of systemic diseases,
including diabetes mellitus, vascular disease, and kidney disorders, also damage
nerves and neuronal cells. Unlike the CNS, the PNS can regenerate both neurons
and nerve circuitry.
 “We know that damaged peripheral nerves regenerate,
but regeneration is not synonymous with recovery,” said Timothy Cope, Ph.D.,
professor and chair of the Department of Neuroscience, Cell Biology, and Physiology
in WSU’s
Boonshoft School of Medicine, director of the school’s new Comprehensive
Neuroscience Center, and principal investigator on the PPG. “Neither sensation
nor movement return to pre-injury levels after nerve regeneration. Although regeneration
of the PNS is necessary to restore voluntary movement, injury initiates changes
in the spinal cord that do not reverse with regeneration. Problems remain in
timing and strength of muscle contraction, problems that are essential to normal
movement.”
The goal of Wright State’s Program Project Grant is “to understand
how injury, regeneration and alterations in neural activity affect synaptic
and network function and to explore the mechanisms that either promote or impede
recovery,” said Cope. “The wide array of approaches and expertise
that we have as a team is likely to accelerate our understanding because we
can attack the problem of limits on regeneration with greater insight and technical
expertise than any one of us could achieve alone.”
Cutting-edge methodologies will be shared across the five
projects. Studies
will examine neurons and synapses using electrophysiological tools to evaluate
their function. Microscopy and associated imaging techniques will assess structure
and changes in protein expression.
“Collaboration with the other team members is critical to placing our
findings in the context of functional and structural changes that are occurring
in the CNS and PNS after nerves regenerate,” adds Dr. Fyffe, Ph.D., associate
dean for research affairs.
“Essential details about the mechanisms underlying changes following
PNS injury are largely unknown and must be obtained in order to develop clinical
applications to many common human conditions, including spinal cord injury,” adds
Dr. Cope. “How can we get these neural circuits to operate normally,
to communicate the way they used to? Our research niche focuses on the limits
to recovery after nerve regeneration.”
Affirming our goals, our resources and our expertise
“Getting this grant places us in an elite category,” says Howard
M. Part, M.D., dean for the Boonshoft School of Medicine. “Our team’s
impressive accomplishment reflects the hard work and dedication of our outstanding
scientists, as well as the continued support of our community, especially from
The Kettering Fund and from the Oscar Boonshoft family.”
Grants received from these sources helped coordinate neuroscience research and
recruit additional outstanding research faculty to Wright State. The Kettering
Fund has supported biomedical research at the Boonshoft School of Medicine since
1998 and was instrumental in advancing several key research areas at the medical
school.
In February, the school announced the formation of a Comprehensive Neuroscience
Center (CNC) for improving research of neurological, developmental, cognitive,
psychiatric and trauma-induced nervous system disorders. The CNC was made possible
through a grant from the Boonshoft Innovation Fund, established when Oscar
Boonshoft, a local philanthropist and long-time supporter, gave Wright State
University School of Medicine a gift of $28.5 million dollars in 2005. His
goal was to provide new resources to spur innovative ideas and programs that
would propel the school to national leadership in medical education, patient
care and research.
The newly established center integrates teams of scientists and clinicians
across several disciplines—on and off campus—to collaboratively
address fundamental issues in both basic science and clinical neuroscience
research. Actively involved are faculty in the fields of biochemistry, cell
biology, molecular biology, neuroscience, pharmacology, physiology, psychiatry,
psychology and toxicology.
“The CNC will advance our research of the nervous system at levels ranging
from cellular and molecular mechanisms to behavior,” said Cope.
“The Program Project Grant has, in effect, affirmed our goals, our resources
and our expertise. The vision for this collaborative center is to continue
to build upon our core strengths and infrastructure as well as leverage strategic
resources,” said Part. “We see neuroscience research as a significant
growth area and an important component in educating our students and advancing
patient care.”
# # #
Detailed scientific information available at www.med.wright.edu/cnc/ppg
The Program Project Grant recently awarded to five Wright State University
researchers by the National Institute of Neurological Disorders and Stroke
reaffirms that there is strength in numbers in scientific endeavors. It is
the power of shared experience, shared expertise, technology, equipment and
resources that are at the foundation of a Program Project Grant. Drs. Francisco
Alvarez, Timothy Cope, Kathrin Engisch, Robert Fyffe and Mark Rich bring decades
of combined expertise to the pursuit of their common interest. Following are
specifics about the researchers’ five individual projects by which they
endeavor to better understand the recovery—or lack of it—from neurotrauma.
Project One: Circuit Plasticity
Timothy Cope, Ph.D.
Professor and Chair, Department of Neuroscience, Cell Biology and Physiology,
Director, Comprehensive Neuroscience Center, Program
Project Grant principal investigator
“After nerve damage and regeneration, we lose the stretch reflex in
affected muscles, adversely affecting our ability to control movement. We theorize
that damage to the PNS creates problems in spinal/neural circuits which do
not reverse after nerve regeneration.” More.
Project Two: Excitatory/Inhibitory Balance
Francisco J. Alvarez, Ph.D.
Associate Professor of Neuroscience, Cell Biology and Physiology
Director of Imaging Core Facilities
“Motoneurons control the activity in our muscles, but their function
is in turn modulated by a fine balance between excitatory and inhibitory influences.
We suspect that deficits in reacquiring this balance following nerve injury
and regeneration are partly responsible for the incomplete restoration of motor
function.” More.
Project Three: Synaptic Plasticity
Mark Rich, M.D., Ph.D.
Associate Professor of Neuroscience, Cell Biology and Physiology
“Injury changes how the synapses transmit at the neuromuscular junction
and we theorize that reduced cellular activity at the time of injury adversely
impacts signaling strength.” More.
Project Four: Molecular Regulation of Release
Kathrin Engisch, Ph.D.
Associate Professor of Neuroscience, Cell Biology and
Physiology
“We are examining the underlying molecular mechanism caused by the change
of cellular activity. The process at the molecular level indicates that the
protein Rab3A plays a major regulatory role.” More.
Project Five: Postsynaptic Excitability
Robert E. W. Fyffe, Ph.D.
Associate Dean for Research Affairs
“Our laboratory will use new imaging techniques to help determine how
the excitability and electrical properties of motoneurons are regulated after
nerve injury.” More.
For more information or to arrange for interviews, please contact
Office of Public Relations, Boonshoft
School of Medicine, (937) 775-2951. |
