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.
Neuromuscular hyperexcitability syndromes are a group of neuromuscular disorders due to hyperexcitable nerves or muscles. Patients typically present with myalgia, muscle cramps or muscle stiffness accompanied by involuntary muscle twitching. Neuromuscular hyperexcitability disorders include rippling muscle disease (RMD) and various peripheral nerve hyperexcitability (PNH) syndromes (e.g. cramp-fasciculation syndrome, Isaacs syndrome and Morvan syndrome). RMD can be genetically determined (CAV3 or PTRF mutations) or less commonly, immune-mediated. Voltage-gated potassium channel (VGKC)-complex autoantibodies are known to cause PNH syndrome. Dr. Liewluck is interested in the autoimmune basis and treatment of RMD and PNH syndromes.
Congenital myasthenic syndrome (CMS) is a genetically heterogeneous group of primary neuromuscular junction disorders. Most CMS patients develop fatigue and limb, ocular or bulbar weakness in their childhood; however, some may have adult-onset symptoms, which are clinically indistinguishable from patients with seronegative myasthenia gravis. Pyridostigmine (Mestinon) is a standard treatment for seropositive and seronegative myasthenia gravis, but it may be ineffective or worsen myasthenic symptoms in some CMS patients. Dr. Liewluck is interested in albuterol therapy in CMS patients who do not respond or respond poorly to Pyridostigmine. He and his former mentor, Dr. Andrew G. Engel, have recently reported the beneficial effects of albuterol in CMS patients due to endplate acetylcholinesterase deficiency and patients with Dok-7 myasthenia.
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.