emotional effects of stroke.  He assesses neurobehavior in patients with focal
cerebrovascular lesions and vascular dementia. 

Jeffrey L. Bennett, MD, PhD
Optic Neuritis.  Optic neuritis (ON) is the most common clinically-isolated
demyelinating syndrome, and is the presenting feature in approximately 25% of
individuals with multiple sclerosis (MS).  Dr. Bennett is attempting to identify the
primary target of the humoral immune response in ON and MS.  His laboratory
utilizes a RT-PCR protocol to amplify the expressed variable-region sequences of
single B-lymphocytes and plasma cells isolated from ON CSF by fluorescence-
activated cell sorting.  The B-lymphocyte and plasma cell heavy- and light-chain
pairings found in vivo are reconstituted in vitro to produce a panel of recombinant
monoclonal antibodies (mAbs) whose specificity is determined by
immunocytochemistry, immunoblotting, and screening of white matter and random
peptide expression libraries.  Since many patients with ON do not develop MS, these
studies will allow identification of clinical and molecular risk factors that may point
to the ultimate cause of human demyelinating disease and allow physicians to
identify at-risk individuals, to diagnose MS at the earliest stage of disease and to
treat patients with therapies designed to modify or even cure disease.
 
Occult Chorioretinal (OC) Disorder.  Acute zonal occult outer retinopathy, multiple
evanescent white dot syndrome, acute macular neuroretinopathy, acute idiopathic
blind spot enlargement syndrome, multifocal choroiditis, punctate inner
choroidopathy and diffuse subretinal fibrosis syndrome are a group of chorioretinal
inflammatory disorders of unknown etiology that mimic optic neuropathy.  These
disorders possess common clinical features, and affected individuals may evolve
from one condition to another.  Dr. Bennett’s laboratory has identified clones in a
human uveoretinal cDNA expression library and a random peptide library whose
products react with serum or immunoglobulins from OC patients.  Using molecular
biologic techniques, the lab screens candidate antigens with sera from OC and
control patients to characterize disease-relevant clones.  Identification of OC-
specific markers will help classify occult chorioretinal disorders as a specific
nosologic entity.
 
Patrick J. Bosque, MD
Dr. Bosque’s research is directed at chronic wasting disease, Creutzfeldt-Jakob
disease and other prion disorders of human and animals.  Dr. Bosque also studies
the role of protein misprocessing in various neurodegenerative diseases.
 
Mark P. Burgoon, PhD
Dr. Burgoon’s research investigates the unknown etiology of multiple sclerosis (MS)
by examining the humoral immune response in the CNS of MS patients. The
persistence of increased IgG in the brains and CSF of MS patients, observed as
intrathecally synthesized oligoclonal bands, suggests a continuous antigen-driven
immune response. The IgG response in the brain and CSF MS patients is being
dissected to determine the antigenic targets in archival acute plaques. These
unbiased studies of the intrathecal humoral response can potentially identify an
antigen in MS and ultimately the cause of disease.  Dr. Burgoon’s laboratory also
uses recombinant antibodies and biopanning techniques to analyze molecular
features of the IgG response in subacute sclerosing panencephalitis (SSPE), a proof
of principle model in which the antigen-driven humoral response is directed against
measles virus, the cause of the disease.
 
Penny Clarke, PhD
Using reovirus infection of the mouse CNS and heart, Dr. Clarke studies viral-
induced apoptosis and signaling pathways.  Apoptotic and cell signaling pathways
involved in reovirus-induced pathogenesis are identified and studied in vitro using
primary neuronal and myocyte cultures and other established cell lines.  The lab has
demonstrated that reovirus-induced regulation of the transcription factor nuclear
factor kappa B (NF-kB) is required for apoptotic cell death in virus-infected cells.
Reovirus-induced apoptosis requires both activation of NF-kB early after infection
and at a later phase of regulation when activation of NF-kB is blocked.  The lab has
also shown that activation of both c-Jun N-terminal kinase (JNK) and the JNK
dependent transcription factor c-Jun are associated with reovirus-induced cell death,
and that reovirus-induced apoptosis is mediated by members of the tumor necrosis
factor family of death inducing ligands, which bind to cell surface death receptors
resulting in Fas activated death domain (FADD)-dependent activation of cellular
caspases.  By inhibiting signaling pathways required for virus-induced cell death, it
may be possible to reduce virus-induced injury and disease.  Finally, Dr. Clarke's
studies have shown that reovirus sensitize cells derived from various human cancers
to TRAIL-induced apoptosis by a mechanism that involves an increase in activation
of caspase 8.  These studies demonstrate a potential to use reovirus and TRAIL as
combination therapy for human cancer.
 
Randall J. Cohrs, PhD
Varicella zoster virus (VZV) is a ubiquitous neurotropic alphaherpesvirus that
typically causes childhood chickenpox, becomes latent in cranial nerve, dorsal root
and autonomic nervous system ganglia, and reactivates during a declining T-cell
response to produce shingles.  Dr. Cohrs studies the molecular mechanism by which
VZV latency is established and maintained, and the steps involved in virus
reactivation.  Dr. Cohrs’ laboratory uses state-of-the-art techniques including
genomics (expression microarrays) and proteomics (protein identification) as well as
more standard cDNA analysis by RT-PCR to investigate the state of virus
transcription in latently infected human ganglia.  After latently transcribed VZV
genes have been identified, their regulation and function of the encoded protein is
analyzed.  A more complete understanding of virus latency will aid in development
of steps to prevent virus reactivation.
 
John R. Corboy, MD
Dr. Corboy's research involves immunotherapies for multiple sclerosis (MS) patients.
These studies utilize FDA approved therapies in novel settings and experimental
agents.  He also studies the role of anti-oxidants, especially uric acid, as it relates to
progression of MS.
 
Denise M. Damek, MD
Dr. Damek clinical research interest focuses on experimental drug therapy of CNS
tumors.  Ongoing clinical trials in the neuro-oncology program include investigation
of novel drugs, new combinations of chemotherapy agents, innovative methods of
drug delivery, innovative approaches of radiation therapy, immunotherapy to
enhance T-lymphocyte stimulation, and gene therapy using retroviral gene transfer.
 
Christopher M. Filley, MD
Dr. Filley is the Interim Director of the Alzheimer’s Disease and Cognition Center
(ADCC), established in 2006, and in this capacity he oversees research projects on
functional MRI of normal cognition, early diagnosis of AD using functional MRI,
and pioglitazone therapy for mild cognitive impairment in patients with metabolic
syndrome.  He is the author of the textbook Neurobehavioral Anatomy, now in its
second edition, and currently participates in research on cognitive aspects of
systemic lupus erythematosus and traumatic brain injury.  A unifying theme of Dr.
Filley's research is the behavioral neurology of cerebral white matter, including
neurologic, psychiatric, neuropsychological, neuroimaging, and neuropathological
aspects of disorders such as toluene leukoencephalopathy and multiple sclerosis. He
has formally proposed the concept of "white matter dementia" to call attention to
cognitive deficits attributable to white matter involvement, described in his second
book The Behavioral Neurology of White Matter.
 
Lauren C. Frey, MD
Dr. Frey is interested in the prediction of epilepsy after traumatic brain injury (TBI).
Only ~20% of people who survive severe TBI develop epilepsy. Developing a method
to predict which survivors will develop epilepsy offers clues about changes in brain
structure necessary for epilepsy. It will also allow physicians to identify and
aggressively treat TBI survivors at highest risk of developing epilepsy.
 
Donald H. Gilden, MD, Chairman
Varicella Zoster Virus/Simian Varicella Virus.  The neurovirology laboratory studies
the physical state of varicella zoster virus (VZV) nucleic acid and viral gene
expression during latency in human ganglia.  Studies include state-of-the-art
technologies such as polymerase chain reaction, cDNA preparation and microarray
to analyze VZV transcription.  Interaction of VZV proteins with other virus and
cellular proteins are also being examined.  In parallel, a model system of varicella in
primates produced by simian varicella virus (SVV) is used to study pathogenesis and
latency.  Finally, the neurovirology laboratory uses diagnostic tests to understand
and treat the neurological complications of zoster, including postherpetic neuralgia
and other complications of  VZV reactivation such as myelopathy and vasculopathy.
 
Multiple Sclerosis.  Dr. Gilden directs the multiple sclerosis (MS) laboratory. His
laboratory uses molecular immunology techniques to determine the cause of MS.
Cutting-edge methodologies have been developed to examine the antigenic targets
of the IgG antibody present in MS brain and CSF. The techniques include single cell
PCR to identify IgG sequences utilized in MS brains, synthetic antibody production,
and phage-displayed library panning to isolate high-affinity antibodies and antigens
from brain. Subacute sclerosing panencephalitis (SSPE) is being used as an
experimental paradigm to demonstrate these new techniques and to develop the
sensitivity required for studies of MS.
 
Deborah A. Hall, MD
Dr. Hall's studies the etiology, diagnosis and treatment of cerebellar ataxia.  She is
currently studying genetic mutations in movement disorders, particularly mutations
in the fragile X mental retardation gene.  Her goal is to define the prevalence of
mutations of the FMR1 gene in populations with tremor, ataxia, and/or parkinsonism.
She collaborates on studies which investigate the role of exercise and physical
therapy in Parkinson disease, and also participates in large, multi-center clinical trials
in various movement disorders.
 
Richard L. Hughes, MD
Dr. Hughes has participated in multiple clinical trials on acute stroke resuscitation,
secondary prevention of stroke and the detection of intracranial aneurysms.  Current
trials include treatment of intracerebral hemorrhage with activated Factor VII, the use
of warfarin and aspirin in heart failure, and treatment of insulin resistance to reduce
stroke.  He works with the Colorado Department of Heath and Environment to
establish a statewide registry to help design and implement a statewide stroke
system in Colorado.
 
Maureen A. Leehey, MD
Dr. Leehey studies the etiology and treatment of neurodegenerative disease.  She
and her collaborators recently discovered the Fragile X Associated Tremor/ Ataxia
Syndrome, which affects about 1 in 10,000 men over age 50.  Dr. Leehey directs
multiple clinical trials designed to offer novel medical therapy and to uncover the
etiology and genetics of various movement disorders.   As a Lead Investigator for
the Parkinson’s Study Group, she is working to identify susceptibility genes that
contribute to the development of Parkinson’s disease.  Dr. Leehey collaborates with
Dr. Curt Freed, a neuroscientist who directs the UCHSC Parkinson’s Disease (PD)
Neurotransplantation Program, which has contributed greatly to our current
knowledge of the effects of neurotransplantation in PD.  Dr. Leehey and her
colleagues recently uncovered the genetic etiology (a prion mutation) of a large
family with a rare neurodegenerative disease. She works with other collaborators to
elucidate neuropsychological changes in Huntington’s disease.
 
Ravi Mahalingam, PhD
Dr. Mahalingam’s laboratory studies varicella pathogenesis and latency.  Studies
include the use of state-of-the-art technologies such as polymerase chain reaction,
cDNA analysis and array analysis to study varicella transcription and the location of
varicella within the ganglia during latency. A cosmid-based approach is also used to
generate mutant varicella virus in an animal model.  Finally, the laboratory uses
diagnostic tools to understand neurological complications of zoster including
postherpetic neuralgia.
 
Hans E. Neville, MD
Dr. Neville enrolls ALS patients into clinical trials.  This multi-center research project
evaluates the efficacy and tolerability of early versus late non-invasive positive
pressure ventilation in ALS patients.
 
Bjorn Oskarsson, MD
Dr. Oskarsson participates in clinical trials to study diagnostic and therapeutic
strategies for ALS.
 
Gregory P. Owens, PhD
Multiple sclerosis (MS) is a CNS inflammatory disease of unknown cause.  Dr.
Owens’ research investigates the role of B cell immunity in the pathogenesis of MS.
To better understand the nature of this response, they have used fluorescence-
activated cell sorting and single cell PCR to analyze the B and plasma cell populations
infiltrating the CNS of MS patients.  The features of the B cell repertoire are indicative
of a targeted and antigen driven response in MS.  They have generated a panel of
monoclonal recombinant antibodies from plasma cell clones identified in MS CSF and
are using recombinant antibodies for immunological screening to identify disease-
relevant MS antigens.
 
Victoria S. Pelak, MD
Dr. Pelak’s research investigates cortical visual processing, with a particular interest
in the effects of aging and dementia on visual motion processing. She is exploring
new methods to diagnose and track cortical visual dysfunction in early Alzheimer’s
disease (AD). Traditionally, it is believed that visual processing deficits occur in the
middle or late stages of AD. Recent studies from her Visual Perception Laboratory
have demonstrated that visual processing deficits (as detected by a novel virtual task
of kinetopsic 3D object processing developed by her research group) may be readily
detectable in the very early stages of AD; this may have implications for predicting
progression from mild memory impairment to AD. Additional ongoing investigations
include studies of the effects of testosterone on visual motion/object/spatial
processing and studies of visual hallucinations associated with degenerative
disorders and vision loss. Methods of assessment include psychophysical testing
using immersive virtual reality technology in her Visual Perception Laboratory and
functional MRI techniques at the UCHSC Brain Imaging Center.
 
Dianna Quan, MD
Dr. Quan is involved in clinical trials to study postherpetic neuralgia, ALS, and
neuromuscular dysfunction in critical illness.
 
Steven P. Ringel, MD
Dr. Ringel’s current investigative activities include the development of an economic
model to perform cost-effectiveness analyses of tests and treatments in ALS,
outcome studies in ALS using a national ALSCARE community database, and a
randomized trial to evaluate the effect of non-invasive ventilation in ALS.  He is also
currently analyzing the results of a Community Tracking Study Physician Survey
which explores factors that influence physician attitudes and performance.
 
Yvonne D. Rollins, MD, PhD
Dr. Rollins is a principal investigator for ALS clinical trials of CoQ10 and minocycline,
early intervention with NIPPV and Pompe compassionate use of Myozyme, a
recombinant enzyme therapy.
 
Archana Shrestha, MD
Dr. Shrestha’s studies medically refractory epilepsy and epilepsy surgery.  She also
is interested in women’s issues in epilepsy and the influence of female hormones on
seizures and epilepsy.
 
Mark C. Spitz, MD
Dr. Spitz’ clinical research includes epilepsy that begins in the elderly, psychiatric
aspects of epilepsy and physical injuries that occur from seizures.  Dr. Spitz is
involved in several ongoing medication trials.
 
Laura Strom, MD
Dr. Strom’s studies autonomic dysfunction and apnea in patients with refractory
epilepsy and its correlation with sudden unexpected death in epileptic persons
(SUDEP).  She is an active member of the SUDEP task force which studies
populations at risk.  Her research also includes outcome measures in patients after
temporal lobectomy, and a developing study on the effects of Lamictal withdrawal.
 
Kenneth L. Tyler, MD
Dr. Tyler’s laboratory uses both in vivo and in vitro models to study the molecular
and genetic basis of viral pathogenesis and viral-induced cell death. A major
research effort investigates the mechanisms by which viruses induce apoptosis.
Current projects include: (1) investigating the role played by specific viral genes and
the proteins they encode in triggering apoptosis; (2) identifying the role of apoptosis
in mediating virus-induced tissue injury in various target organs, including the CNS
in vivo (3) defining the cellular pathways by which apoptosis is induced in virus-
infected cells.  Studies of cellular mechanisms of apoptosis currently involve
investigations into virus-induced alterations in MAP kinase and other signal
transduction pathways, transcriptional activators including c-Jun and NF-kB, the
use of genomic microarray and proteomic technology to identify genes and proteins
altered during viral infection of target cells, and identifying death-receptor and
mitochondrial caspase signaling pathways.  Further details about specific personnel
and their projects can be found on the Tyler lab web site at:
http://www.uchsc.edu/sm/neuro/tylerlab.  Ongoing clinical research includes
projects sponsored by the Collaborative Antiviral Study Group, the AIDS Clinical
Trials Group, and the Neurologic AIDS Research Consortium in areas of West Nile
virus infection, herpes encephalitis, and the neurological complications of HIV
infection.