Welcome to the Department of Neurology

Principal Investigators C-F

Penny Clarke, PhD
Using reovirus infection of the mouse CNS and heart, Dr. Clarke studies cellular signaling pathways involved in viral-induced apoptosis. 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. Ongoing studies use microarray analysis to identify additional genes and signaling pathways that are activated in the brain following infection with reovirus and West Nile virus and may provide novel therapeutic targets for viral encephalitis. 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 look at novel, still unapproved agents, as well  FDA approved therapies in novel settings. He is the Director of the Rocky Mountain MS Center Tissue Bank, one of the world’s largest MS-specific banks, providing MS tissues to researchers all over the world. In collaboration with others on campus, he also studies biomarkers of disease activity in 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 has conducted research in many areas of behavioral neurology, including the dementias, traumatic brain injury, focal neurobehavioral syndromes, and neuropsychiatric disorders. Early in his career he participated in many observational studies and clinical trials in Alzheimer's Disease, and since 2006 he has organized research projects within the Alzheimer’s Disease and Cognition Center (ADCC) on functional MRI of normal cognition, early diagnosis of Alzheimer’s Disease with functional MRI, and diffusion tensor imaging studies of fragile X tremor ataxia syndrome. Throughout his career, the unifying theme of Dr. Filley's research has been the behavioral neurology of white matter, as manifested by a wide range of disorders such as toluene leukoencephalopathy, multiple sclerosis, and systemic lupus erythematosus. He has formally proposed the concept of white matter dementia to call attention to and characterize cognitive dysfunction attributable to white matter involvement, described in his book The Behavioral Neurology of White Matter, now in its second edition.

Lauren C. Frey, MD
Dr. Frey is interested in the processes of the development of epilepsy after traumatic brain injury. Only about 20% of people who survive severe traumatic brain injury will develop epilepsy. Developing tools to predict which survivors will develop epilepsy offers clues about the changes in brain structure necessary for the occurrence of epilepsy. It will also allow physicians to identify, and aggressively treat, TBI survivors at highest risk of developing epilepsy in hopes of preventing seizures altogether. Dr. Frey is a Faculty Associate of the Colorado Injury Control Research Center and a Faculty Affiliate in the University of Colorado’s graduate Neurosciences Program.

Principle Investigators G-M

Donald H. Gilden, MD
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.

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.

Leila J. Jackson, PhD
In the past few years, several new efficacious therapies have emerged for treatment of patients with neuroimmunological disorders such as Multiple Sclerosis (MS) and Neuromyelitis Optica (NMO). Dr. Jackson’s research lab focuses on the mechanisms of action of these therapeutics, as well as discovering potential novel therapies for patients with neuroimmunological disorders including MS, NMO and others. This lab researches immune mechanisms mediating neurological disorders to further understand how immune cells orchestrate disease initiation, progression, stability, and remission. Dr. Jackson studies innate and adaptive human immune cells and their ability to communicate with (activate or repress) cells within the brain and central nervous system in the context of disease. The results from these studies will potentially lead to a better understanding of the current and emerging therapies in neuroimmunological disorders providing rationale for combination therapies or novel therapeutics for effected patient populations.

Olga S. Klepitskaya, MD
Dr. Klepitskaya’s research interests include surgical treatment for movement disorders, specifically Deep Brain Stimulation (DBS), and behavioral aspects of Parkinson’s disease (PD), such as Dopamine Dysregulation Syndrome, cognitive and behavioral outcomes after DBS. She is involved in clinical trials of new medications and new types of surgical treatments for PD and other movement disorders.

Benzi M. Kluger, MD, MS
Dr. Kluger’s research involves the application of neuropsychological testing, transcranial magnetic stimulation (TMS) and magnetoencephalography (MEG) to understand the pathophysiology of the non-motor symptoms of movement disorders and other neuropsychiatric illnesses. His research currently focuses on understanding the neurophysiologic basis of fatigue, particularly as it affects patients with Parkinson’s disease. Other interests of Dr. Kluger include behavioral neurology, volitional action and conscious perception.

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 (FXTAS), which affects about 1 in 10,000 men over age 50, especially grandfathers of children with fragile X syndrome. While Dr. Leehey’s major research effort is to characterize FXTAS, she directs multiple clinical trials designed to offer novel medical therapy and to uncover the etiology and genetics of various movement disorders, especially Parkinson disease. Dr. Leehey collaborates closely with basic scientists to translate their efforts into meaningful interventions. She and her colleagues recently uncovered the genetic etiology (a prion mutation) of a large family with a rare neurodegenerative disease. Her efforts are funded by the National Institutes of Health, Michael J. Fox Foundation, and other governmental and private agencies.

Teerin Liewluck, MD
Muscular dystrophies and non-inflammatory myopathies are genetically heterogeneous disorders primarily affecting skeletal muscle, which lead to progressive muscle weakness and some extramuscular problems.  Myofibrillar myopathies are a group of muscular dystrophies that share the common pathological features of early myofibrillar degeneration. Dr. Liewluck is interested in the heterogeneity and complexity of genetic basis of these primary muscle disorders. Dysferlinopathy is a muscular dystrophy caused by mutations in dysferlin-encoding gene (DYSF). DYSF mutations were reported to cause amyloid myopathy without systemic amyloidosis (isolated amyloid myopathy). He and his former mentor, Dr. Margherita Milone, have recently described a novel form of isolated amyloid myopathy due to ANO5 mutations. ANO5 mutations were previously reported to cause limb-girdle and distal muscular dystrophies.

Ravi Mahalingam, PhD
Dr. Mahalingam’s laboratory studies varicella pathogenesis and latency and reactivation. Studies include the use of state-of-the-art technologies such as polymerase chain reaction, cDNA analysis and multiplex PCR analysis to study varicella transcription during primary infection as well as reactivation. Other studies include the role of cell-mediated immunity in the regulation of varicella latency and reactivation. A bacmid-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.

Augusto A. Miravalle, MD

Dr. Miravalle is currently involved as Principle Investigator or Sub Investigator in multiple clinical trials at the University of Colorado, with participation in additional studies in the near future. Many of these studies involve novel immunotherapies as well as cutting edge therapeutic approaches for the treatment of MS.  Dr. Miravalle has a particular interest in imaging studies evaluating early detectors for future disability in MS patients. He is active in the local, regional and international community, lecturing frequently in the United States and Europe.

Principal Investigators N-R

Maria A. Nagel, MD
Dr. Nagel studies the molecular mechanisms of varicella zoster virus latency and reactivation. Using a novel multiplex PCR assay, Dr. Nagel is characterizing viral transcripts in latently-infected human ganglia and the kinetic classes of the VZV genes during reactivation

Douglas E. Ney, MD
Dr. Ney’s clinical research interests focus on innovative treatments for primary brain tumors and metastatic disease including novel chemotherapeutic agents as well as molecularly targeted agents for the treatment of malignant glioma.

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 UCDSOM Brain Imaging Center

Sharon N. Poisson, MD
Dr. Poisson’s research focuses on etiology, prevention and treatment of transient ischemic attack (TIA) and stroke. She previously conducted research evaluating gender roles in the treatment of carotid stenosis in TIA, as well as the role of intracranial large vessel stenoses in TIA. She has a specific interest in the increasing trends of ischemic stroke in young adults, and is studying the role of atherosclerotic risk factors and race as potential causes of this trend. In addition, she has an interest in the quality of hospital care of patients with ischemic and hemorrhagic stroke. 

Huntington Potter, PhD
Our current research is devoted to laboratory and clinical investigation of neurodegenerative diseases, particularly Alzheimer’s disease (AD) and trisomy 21/Down syndrome (DS), which also induces AD by age 40. We hypothesized and showed that AD patients develop trisomy 21 and other aneuploidy cells, including neurons, during the course of their life and thus that AD is a mosaic form of DS. We recently found the mechanism by which aneuploidy develops in AD: the Ab peptide inhibits certain microtubule based kinesin motor proteins and thus prevents the transport of key cellular components, including vesicles, chromosomes, and microtubules themselves to their proper locations in the cell. As a result, dividing cells mis-segregate their chromosomes, generating aneuploid, including trisomy 21 cells in AD patients, cells in culture, and transgenic AD mice. Neurons also fail to localize neurotrophin and neurotransmitter receptors to the cell surface, resulting in the poor neuroplasticity. We have also found aneuploid neurons and other cells in patients and mouse models of Niemann Pick C and Fronto-Temporal Dementia, suggesting that chromosome mis-segregation may underlie many different forms of neurodegeneration. We are currently investigating the mechanism of chromosome mis-segregation and searching for means to prevent or reverse it. We also hypothesized that rheumatoid arthritis patients, who seldom develop AD release an endogenous protective molecule and showed that GMCSF and GCSF, over produced in RA, reversed AD pathology and cognitive deficits in a mouse model of AD. We are currently carrying out a clinical trial to test the safety and efficacy of human GMCSF (Leukine) in AD patients and have proposed a similar trial in DS.

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 focus heavily on quality, safety and effectiveness studies. He has organized department-wide inpatient and ambulatory performance improvement projects and is assisting each subspecialty section of the department in the development of quality and safety projects. He continues to be involved in multi-university therapeutic trials in ALS. A current trial involves testing the efficacy of diaphragmatic stimulation to assist ventilation in ALS.

Principal Investigators S-Z

Teri L. Schreiner, MD, MPH
Dr. Schreiner's research interests include genetic and environmental triggers of pediatric multiple sclerosis, immunotherapies for multiple sclerosis (MS) patients, and quality of life in pediatric patients with demyelinating diseases. In collaboration with others on campus, she also studies biomarkers of disease activity in MS.

Archana A. Shrestha, MD
Dr. Shrestha 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 A. Strom, MD
Dr. Strom is currently working on investigator initiated clinical research with two different areas of interest. She continues to be very interested in the influence on patients with medically refractory epilepsy of the autonomic nervous system. She is working with resident physician, Dr. Peter Bergmann on a project to investigate how heart rate variability may predict changes in heart rate during seizure activity. Her second area of active interest is in the impact on epilepsy of hormones. She is working with another resident, Dr. Danielle McDermott to develop a research project looking at fluctuations in sex hormone levels in patient with medically refractory epilepsy. In addition to clinical research, Dr. Strom is primary investigator for several industry sponsored clinical trials of novel anti-epileptics as well as novel uses for anti-epileptic drugs which are already on the market.

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. 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.

Timothy L. Vollmer, MD
Dr. Vollmer is the Director of Neurosciences Clinical Research.  He is currently involved as Principles Investigator of Sub Investigator in 26 clinical trials in multiples sclerosis at the University of Colorado, with participation in additional studies in the near future.  Many of these studies involve immunotherapies for the treatment of this disease.  Dr. Vollmer has a particular interest in investigator initiated clinical trials focusing on optimizing current therapies and combinations of therapies.  To date, Dr. Vollmer has completed over 100 clinical studies in MS.  He is active in the local, regional and international communities conducting research in MS.  He lectures frequently in the United States and Europe.

Xiaoli Yu, PhD
Dr. Yu’s research investigates the specificity of IgG in patients with multiple sclerosis (MS) using phage-displayed peptide libraries approach. A hallmark of MS is the persistence of oligoclonal IgG and elevated numbers of B cells in the CNS. Our published studies have demonstrated the antigen-driven response of clonally expanded B cells in MS. We are using recombinant antibodies generated from these B cells to identify peptide epitopes/mimotopes by panning phage-displayed random peptide libraries. The specificity of the peptides is confirmed by ELISA, immunoblot and competitive inhibition assays. By applying a highly sensitive phage mediated immuno-PCR technique, these peptides are screened for bindings to IgG in multiple MS patients. MS peptides can then be used to determine the corresponding protein antigens using bioinformatics approach. Identification of MS antigens has the potential to determine the cause of disease, and to develop strategies for diagnostic and therapeutic intervention.