Dr. Alvarez’s research interests include optimizing treatment decisions for patients with multiple sclerosis and related diseases and especially in clinical studies involving immunotherapy for the treatment of this disease. Additionally, Dr. Alvarez is interested in biomarkers to improve treatment decisions and diagnosis of neuroimmunological diseases.
Dr. Anderson’s research is focused on stroke prevention and the cognitive and emotional effects of stroke. He assesses neurobehavior in patients with focal cerebrovascular lesions and vascular dementia.
Alexandra Atwood's research interests include barriers to receiving care in patients with non-epileptic seizures, as well as neuropsychological outcomes in post surgical epilepsy patients.
With a background in both clinical epilepsy and health services research, Dr. Baca conducts research focusing on the measurement of health outcomes for people with epilepsy. She conducts patient-centered research to improve access, health disparities, quality of care and health outcomes for people with epilepsy, particularly for vulnerable groups. To date she has conducted projects measuring expectations to adult respective epilepsy surgery, long-term psychosocial outcomes in young adults and adolescents with childhood-onset epilepsy, delays in the timing of pediatric epilepsy surgery, in addition to access and quality of care for veterans with epilepsy. She is now conducting an Epilepsy Foundation American Epilepsy Society funded study of pediatric to adult transitions of epilepsy care. She has received funding from the Epilepsy Foundation, the National Institutes of Health and the Veterans Administration.
Dr. Barry's research interests include etiology, prevention and acute treatment of stroke in children and young adults. She is also interested in developing a transitional model for children with neurological needs graduating to an adult neurologist.
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 uveal retinal cDNA expression library and a random peptide library whose products react with serum or immunoglobulins from OC patients. Using molecular biological 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.
Ms. Berk's research interests are related to projects aimed at improving the quality of life for those suffering with chronic neurologic disease, and their families.
Dr. Berman uses structural and functional imaging techniques to study the underlying pathophysiology of movement disorders including Parkinson disease (PD) and dystonia. His current research projects involve the use of functional MRI (fMRI) and diffusion tensor imaging (DTI) to investigate the changes that occur within basal ganglia circuits in PD and dystonia patients, as well as the use of Positron Emission Tomography (PET) and Electroencephalography (EEG) to investigate inhibitory function in patients with dystonia. Knowledge gained from these investigations will help us better understand the pathophysiology that underlies these chronic neurological disorders. The ultimate goal of these projects is to develop and validate neuroimaging biomarkers for these diseases that will aid our ability to diagnose these heterogeneous disorders and inform treatment development. He is also a lead site investigator for a multi-center natural history and biorepository project in focal dystonia and co-investigator on a study investigating the effects of endurance exercise in PD.
Dr. Bettcher is an Assistant Professor and neuropsychologist in the Department of Neurology, and directs neuropsychology research at the Rocky Mountain Alzheimer’s Disease Center. The overarching goal of Dr. Bettcher’s research program is to elucidate modifiable factors that will inform early treatments for cognitive decline for a wide range of neurodegenerative diseases. Dr. Bettcher’s laboratory focuses on the intersection of innate immunity, Alzheimer’s disease pathology, and cognitive function in late life. Her research utilizes plasma-based and CSF-based multiplex arrays of chemokines, growth factors, and cytokines to delineate how peripheral immune signatures contribute to pathological aging trajectories.
Marius Birlea, MD
I am interested in exploring the epidemiology and social implications of migraine and other primary headaches, including social causation and ways to decrease disability associated with severe headache conditions. The factors involved in the development of chronic headache are multiple and may include frequent reactivation of latent viruses, which can be evaluated by laboratory parameters. Another area of interest for me is searching for laboratory biomarkers that may be associated with migraine and comorbid conditions, including possible blood dyscrasias and cardiovascular disorders. Therapeutic avenues are explored using neuromodulation device Cefaly.
Dr. Bosque’s research is directed at chronic wasting disease, Creutzfeldt-Jakob disease and other prion disorders of humans and animals. Dr. Bosque also studies the role of protein misprocessing in various neurodegenerative diseases.
Dr. Buard is a neurophysiologist interested in motor and cognitive impairments across other neuropsychiatric disorders. She investigates the cortical correlates of these impairments through the use of diverse brain imaging methods (Magnetoencephalography - MEG, Magnetic Resonance Imaging) and using diverse neuromodulation methods (Neurologic Music Therapy - NMT, Transcranial Magnetic Stimulation - TMS). Using translational approaches, her long-term goal is to develop strategies for motor and cognitive rehabilitation. She is currently investigating the use of (1) NMT for enhancing fine motor control in Parkinson’s and Huntington’s disease; (2) MEG as a biomarker of cortical network dysfunction in Traumatic Brain Injury; and (3) TMS as a tool for studying and modifying cortical excitability.
Dr. Burke is interested in research on ketamine use for neuropathic pain states and opioid induced hyperalgesia.
Dr. Brown's training in clinical epilepsy and biomedical research represents her clinical research goals of improving the localization of epileptic networks for surgery and devices as a treatment of epilepsy. She believes that improved localization will enable epileptologists to better assign individual patients to the best individualized therapy, whether that is seizure control devices, resective surgery, or continued medical therapy. She has also been involved with clinical trials for epilepsy. Dr Brown is also interested in helping to improve healthcare safety and quality and is participating in a one year certificate program through the Institute for Healthcare Quality, Safety and Efficiency (IHQSE).
Ms. Cardinal is interested in researching quality and safety outcomes in patient care related to communication among healthcare providers, patients and family members, as well as medication errors.
Aaron Carlson, MD
Dr. Carlson's research interests primarily focus on the equitable delivery of care to neurology patients and in clinical trials. His current project aims to determine the prevalence, demography, and care patterns for multiple sclerosis patients in a population of >15 million, comprising ~75% of the Florida population. His clinical trial experience includes serving as a site PI and sub-investigator for consortium-based and industry-sponsored studies in neuroimmunology.
Virus-induced diseases of the central nervous system (CNS), including the brain (encephalitis) and spinal cord (myelitis) induce significant morbidity and mortality throughout the world. Treatments for these diseases are sub-optimal or non-existent. Dr. Clarke’s laboratory uses clinically important viral pathogens (West Nile virus, Japanese encephalitis virus and herpes simplex virus) to investigate cellular genes and signaling pathways that are up-regulated or activated in the CNS following virus infection and to evaluate these host factors as therapeutic targets for virus-induced CNS disease. Dr. Clarke’s research has identified apoptosis as a key mechanism of virus-induced pathology within the CNS and interferon signaling as a critical component of anti-viral defenses. Dr. Clarke’s research has also demonstrated the generation of a robust neuroinflammatory response in the CNS following virus infection, including the activation of resident immune cells (astrocytes and microglia) and the up-regulation of pro-inflammatory gene expression. The role of this response in viral pathology is currently being investigated.
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 chromosomal immunoprecipitation 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.
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 also interested in identification of individuals at high risk of developing MS, and determining the safety and risks associated with discontinuation of MS therapies. 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.
Dr. Damek’s 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 approaches of radiation therapy, and immunotherapy.
Ms. Darrow is currently involved with the research teams for both the Longitudinal Biomarker Study in memory and dementia, as well as clinical trials with Leukine and Aducanumab.
Dr. DeStefano's research interests include investigating mechanisms and interactions between several neurostimulation devices (e.g. RNS, VNS) used for patients with drug resistant epilepsy. He is also focusing on quality improvement within the epilepsy monitoring unit.
Dr. Dixon is interested in clinical trials for treating adults with spinal muscular atrophy.
Dr. Duntley is actively involved as Principal Investigator in multicenter clinical trials investigating new pharmaceutical treatments in the sleep medicine field. Current research involves using readily accessible but under-utilized data sets such as inpatient telemetry signals to detect sleep disorders and measure sleep quality. Other recent areas of research include biomarkers of sleep need, pathophysiology of Restless Legs Syndrome, and interactions between sleep and Alzheimer’s disease, sleep and depression, and sleep and fatigue.
Dr. Filley has conducted research in many areas of behavioral neurology, including the dementias, traumatic brain injury, focal neurobehavioral syndromes, and neuropsychiatric disorders. Throughout his career, the unifying theme of his research has been the behavioral neurology of white matter, as manifested by a wide range of disorders such as toluene leukoencephalopathy, multiple sclerosis, CADASIL, systemic lupus erythematosus, and fragile X tremor/ataxia syndrome. Dr. Filley has formally proposed the concept of white matter dementia to call attention to the cognitive dysfunction that can be attributable to white matter involvement, and worked to characterize the specific neurobehavioral features of this syndrome, as described in his book, The Behavioral Neurology of White Matter, now in its second edition. His current interests center on the role of disrupted white matter in the etiopathogenesis of neurodegenerative diseases, a perspective that informs the expanded departmental effort to investigate Alzheimer's Disease.
Dr. Foster is interested in clinical research focused on improving quality of life for patients with ALS.
Dr. Frey’s research focuses on neurofeedback, a specific mind-body intervention with a long history of being used with people with refractory epilepsy. She is the Director of the Neurofeedback Clinic at the University of Colorado Hospital, and has published studies looking at the effect of neurofeedback training on seizure control and quality of life in patients with epilepsy.
Dr. Fridman’s research interests focus of identifying therapies for hereditary nerve disorders (also known as Charcot Marie Tooth Disease). Additionally, she is interested in identifying new forms of hereditary neuropathy and in defining biomarkers that can be used to measure progression in these disorders over time.
Dr. Fullard’s research focuses on health services and health outcomes in Parkinson’s disease, as well as disparities in outcomes and care. She is also interested in using technology to improve symptom monitoring and access to care in Parkinson’s disease. Her current projects examine health care utilization in older adults with Parkinson’s disease, factors associated with disability in Parkinson’s disease, and using smart phone applications and wearable devices to track symptoms in Parkinson’s disease.
Multiple sclerosis (MS) is a chronic condition of the central nervous system consisting of inflammatory and neurodegenerative components. Many treatments targeting the immune system have been shown to positively influence the disease course of MS patients,
though there remains a significant variability in patient outcomes. Dr. Gross is interested in learning more about this heterogeneity through the identification of blood, spinal fluid, and imaging biomarkers associated with treatment response and
with neurological decline.
Dr. Hadipour-Niktarash's research interests include multi-scale dynamics and functional network in epileptic brain states, fundamentals of cortical and subcortical oscillations, quantitative EEG, mechanisms of seizure propagation and brain stimulation/neuromodulation.
Trevor H. Hawkins, MD
Dr. Hawkins is interested in the diagnosis, management and clinical progression of genetic forms of ataxia, in particular spinocerebellar ataxia. He is also interested in the use of cannabis in Huntington’s disease and other neurological diseases. He is involved in several clinical trials for treatment of other movement disorders, such as Parkinson’s disease.
With training in both behavioral neurology and movement disorders, Dr. Holden’s research focuses on cognition, behavior and quality of life in parkinsonian conditions. Her current research projects include determining the best methods for predicting and diagnosing dementia in Parkinson’s disease, as well as investigating non-pharmacological treatments for bothersome behavioral symptoms in dementia, such as music therapy. She is interested in developing practical and personally meaningful interventions to improve quality of life for people living with neurodegenerative dementias.
Dr. Hughes has an extensive history of Clinical Research in Cerebrovascular Disease. This includes multiple NIH Multi-Center trials for Cartotid Endarterectomy, Unruptured Aneurysms, PKD-Related Aneurysm natural history, most recently the Wafarin Aspirin trial in heart failure (WARCEF), and the soon-to-be released Insulin Resistence in Ischemic Stroke (IRIS). He has also participated in many industry supported trials, incluing CAPRI (clopidogrel), PROFESS (ASA/Dipyridamole vs. Clopidogrel), Acute Neuroprotection, PFO Closure, and in the earlty rTPA clinical trials.
Over the past 20 years, Dr. Hughes has become more involved in the scholarship of clinical stroke service delivery. After Co-Directing the Colorado Acute Stroke Network to support hospitals' transition to the rTPA era, he has worked on the AHA national committes for the development and implementaion of Primary Stroke Centers, then Comprehensive Stroke Centers, and soon Acute Stroke Ready Centers. He currently sits on the AHA Hospital Accreditation Committee, which oversees all of the stroke and cardiac programs jointly administrated by the AHA and The Joint Commission.
Dr. Kern is interested in several novel diagnostic approaches and treatment options for movement disorders. These areas include investigating potential biomarkers in parkinsonism, including tissue biopsies of skin and colon as well as cardiac imaging (MIBG SPECT scanning). He has an interest in surgical treatments, particularly deep brain stimulation (DBS), investigating optimal patient selection for dystonic tremor and the use of interleaving stimulation. Finally, he is involved in several clinical trials including botulinium toxin and medications.
Dr. Kluger is interested in improving the lives of patients with advanced neurological illnesses through a variety of research approaches. He is investigating the needs of patients and caregivers from a palliative care perspective and testing the efficacy of palliative care interventions for addressing these needs. He is interested in improving our understanding of non motor symptoms, particularly fatigue and cognitive dysfunction, through the use of behavioral, neuroimaging and neurophysiological studies. Lastly, he is interested in exploring non pharmacological approaches to the treatment of non motor symptoms including noninvasive brain stimulation (transcranial magnetic stimulation and direct current stimulation) and complementary and alternative medicine approaches.
Dr. Korb’s research interests include areas of clinical epilepsy specifically the use of continuous electroencephalogram (EEG) monitoring in critically ill patients and the use of advanced imaging techniques (e.g., PET quantification, SPECT analysis, DTI, etc.) for identification of epileptogenic zones as potential targets for epilepsy surgery. He has also been involved with clinical trials for epilepsy. His other areas of research interest include quality improvement for inpatient evaluation and management of neurological emergencies including status epilepticus.
I am interested in seeing progress in multiple facets of care through the treatment plans I implement along with the partnership of the patients. I am also interested in exploring NES in the setting of mental illness and the efficacy of different forms of therapy as treatment measures.
Dr. Leehey studies the etiology and treatment of neurodegenerative disease characterized by movement disorders. She and her collaborators 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. Working with another team of scientists, she uncovered the genetic etiology (a prion mutation) and described the clinical findings of a large family with a rare neurodegenerative disease. Most recently Dr. Leehey is leading research on the effects of cannabidiol (CBD), a component of marijuana, on Parkinson disease. Dr. Leehey continues to she direct multiple clinical trials designed to offer novel medical therapy and to uncover the etiology and genetics of various movement disorders, especially Parkinson disease. She collaborates closely with basic scientists to translate their efforts into meaningful interventions. Her efforts are funded by the National Institutes of Health, Michael J. Fox Foundation, Colorado Department of Public Health and Environment and other governmental and private agencies.
Dr. Leppert utilizes health services research methods to study stroke. Her particular interests include cost-effectiveness evaluation and strokes in young adults.
Dr. Maa is interested in treating medically and surgically refractory epilepsies. He is involved with clinical trials involving the antiepileptic drug development pipeline, but has specific interests in novel therapies including bumetanide and other diuretics, as well as cannabidiol and other phytocompounds used in the treatment of epilepsy. He is currently investigating the use of acupuncture for the treatment of non-epileptic seizures, and has had a long standing interest in the effects of high altitude and patients with epilepsy as well as new onset seizures in travelers to high altitude environments.
Dr. Mahalingam’s laboratory studies varicella pathogenesis and latency and reactivation in an animal model. Studies include the role of cell-mediated immunity in the regulation of varicella latency and reactivation. A bacmid-based approach is used to generate mutant varicella virus to study immune evasion by varicella viruses. State-of-the-art technologies such as multiplex PCR analysis is also used for simultaneous detection of multiple human herpes viruses in biological specimens. Finally, the laboratory uses diagnostic tools to understand neurological complications of zoster including postherpetic neuralgia.
Dr. McConnell's current research interests include an investigation of changes to brain function among patients with cognitive problems, including dementia and Alzheimer's disease. His current research goals include the development of novel treatments for memory, mood, and behavioral problems that will utilize non-invasive brain stimulation.
Dr. McDermott has a strong background in epilepsy surgery, including presurgical evaluation and applications of neuromodulation modalities such as Responsive Nerve Stimulation (RNS). Dr. McDermott’s research focuses and novel applications of neuromodulation optimization of stimulation pathways. Dr. McDermott has created region wide epilepsy registries, linked with electronic medical records, to initiate contraceptive counseling in women with epilepsy, with the aim to implement prospective analysis to guide treatment paradigms. Additional interests include integrative approaches of care to address factors that hinder emotional and physical health of patients with chronic illness.
Ms. McMenamin's research includes clinical trials to advance Disease Modifying Therapy (DMT) in patients with Multiple Sclerosis (MS). Within the context of the clinical trials, the patient centered goals include improved quality of life, with attention to maintaining or improving function and shared decision making about disease management.
Maria A. Nagel, MD
Dr. Nagel specializes in neurovirology and studies how varicella zoster virus (VZV), which causes chicken pox and shingles, causes stroke. Her clinical studies include defining the frequency of VZV in patients with stroke, giant cell arteritis, and atypical facial pain. Her basic science studies focuses on the role of purinergic signaling and inflammation on VZV-induced pathological vascular remodeling.
Dr. Ney’s clinical research focuses on innovative and novel treatments for patients with glioma, central nervous system lymphoma and other primary and secondary brain tumors. Research interests also include histiocytic disorders, quality of life and patient reported outcomes in patients with brain tumors, neurologic complications of cancer and paraneoplastic disorders.
Ms. O'Banion is interested in research that focuses on the etiology, prevention and treatment of stroke, along with an interest in the quality of care of patients with ischemic and hemorrhagic strokes in the acute care setting and determinants of stroke recovery.
Dr. O’Brien is currently involved as an Investigator in the Epilepsy Surgery Quality Improvement project and Sub Investigator in multiple industry sponsored clinical trials of novel anti-epileptics at the University of Colorado.
Debra O’Reilly, PA-C is interested in clinical trials for the treatment of ALS. She is actively involved in a trial investigating the use of diaphragmatic stimulation to assist ventilation in patients with ALS and a new drug in the treatment of ALS. She is also working on a quality improvement project to address and treat depression in patients with neuromuscular disease. Lastly, she is involved in the treatment of myasthenia gravis with Rituximab.
Dr. Orjuela’s research interests include areas of vascular neurology specifically secondary stroke prevention, cryptogenic stroke, inherited cerebrovascular disorders and stroke in children and young adults. Her other areas of research interest include stroke disparities worldwide and stroke systems of care in developing countries.
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.
As a neurologist and CDC-trained medical epidemiologist, Dr. Pastula is interested in the epidemiology of various neurologic and infectious conditions. He has particular interest in neuro-infectious diseases (e.g., meningitis and encephalitis), arboviruses and other vector-borne diseases, emerging infectious diseases, neurotoxicology, and many other acute neurologic conditions. Dr. Pastula also has experience in cluster and outbreak investigations, emergency response, and public health policy.
My research interests include treatment of refractory seizures with surgery and/or medical devices.
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.
Ms. Percowycz's research interests includes the management of acute and chronic headache disorders and quality of life of migraine patients.
Dr. Piquet’s research interests include optimizing diagnosis and treatment for patients with autoimmune neurological diseases; this includes the development of standardized guidelines and protocols for the diagnostic work up and treatment for autoimmune encephalitis. Previously, she has been involved with quality improvement projects focus on the diagnosis and management of patients with acute encephalitis.
Dr. Poisson’s research focuses on etiology, prevention and treatment of transient ischemic attack (TIA) and stroke. She has 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, as well as the role of endothelial activation in stroke in the young. In addition, she has an interest in the quality of hospital care of patients with ischemic and hemorrhagic stroke.
Current research includes a quality improvement project aimed at increasing Neurohospitalist division revenue. Interventions are focused on residents though education and direct feedback. A curriculum for the Neurology residents focusing on the business of medicine and personal and professional development is also in development. Other interventions include regular reporting to faculty for feedback on relative and group performance.
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 aneuploid 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 Abeta 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, and that the aneuploid cells are prone to apoptosis, 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, reverse 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. Finally, we showed some time ago that apoE4, the strongest risk factor for late onset AD, other than age itself, exerts its effect by catalyzing the conversion of monomeric Abeta into the multimeric form that is toxic to neurons and accumulates as amyloid deposits. We are currently searching for molecules that block the catalytic activity of apoE.
Dr. Pratt has been a clinical investigator for many stroke therapy national and international trials, and has worked to decrease time to treatment for area stroke patients.
Peter Pressman is interested in verbal and nonverbal communication in neurodegenerative diseases, particularly the frontotemporal dementias. He is particularly interested in applications of computational linguistics and paralinguistics to the assessment of neurological patients.
Dr. Quan is involved in in clinical trials to study transthyretin familial amyloid polyneuropathy, new clinical therapies in ALS, and neuromuscular dysfunction in critical illness.
Dr. Ragole is interested in the areas where inpatient Neurology and Neuromuscular Disorders overlap, with particular focus on: 1) improving treatments and outcomes for myasthenia gravis, immune mediated neuropathies and immune mediated myopathies; 2) evidence-based practice and guideline development for the treatment of hospitalized patients; and 3) improving clinical decision-making at all levels of education.
Mr. Reynek is interested in research about the impact of headaches on daily life, with a focus on the diagnosis and management of head pain conditions.
Brian Sauer's research interests include the neurobiology of acute autoimmune and neuroinfectious diseases; the pathophysiology and treatment of new onset refractory status epilepticus (NORSE); computer-aided clinical decision making in the diagnosis and treatment of complex neurological disorders; and the design and development of health care networks for the efficient and equitable delivery of acute, inpatient neurological care.
Improved management of patients presenting to the ED with primary headaches, components leading to medication overuse headaches, and non-pharmacological interventions to decrease headache days for migraine patients.
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.
Dr. Seeberger has conducted over 80 clinical trials for the advancement of treatments in movement disorders. Her research has involved patients with Parkinson’s disease, Huntington’s disease, Essential tremor, Dystonia, Tics and Restless Legs Syndrome. Dr. Seeberger has a strong interest in the use of rehabilitation in chronic disease. She has recently been selected as an investigator for a therapeutic trial in asymptomatic Huntington’s disease.
Dr. Shrestha studies women’s issues in epilepsy and changes in seizures and seizure medications during pregnancy, including pharmacokinetic changes in anticonvulsants during pregnancy; the utility and effectiveness of MEG scans in patients undergoing epilepsy surgery evaluation; and therapeutic options in patients with medically refractory epilepsy, including epilepsy surgery, stimulating devices and clinical medication trials. She is also interested in ICU and continuous EEG monitoring and epilepsy in developing countries.
Dr. Sillau's interests include regression, generalized linear models, longitudinal data and mixed models, covariates measured with error, survival and event analysis, non-parametric/semi-parametric methods, clinical trials, sampling, and missing data issues.
Dr. Simpson has multiple quality improvement projects, in both the inpatient and outpatient settings. She has outpatient initiatives that help to reduce admissions and improve patient experience in clinic. On the inpatient side, she is working to improve efficiency and timeliness of acute stroke treatment. She is also the local principal investigator for a national trial involving patients with transient ischemic attack.
Dr. Sladek’s laboratory, since his early publications on the chemical neuroanatomy of mammalian brain, has focused on the unique distribution of the histologically identifiable monoamine neurotransmitters, especially dopamine, norepinephrine, serotonin as well as peptidergic neurons of the hypothalamus including vasopressin, oxytocin, LHRH and others. His laboratory developed dual localization techniques that permitted detailed studies in higher order primates. His interests in the role these neurotransmitters played in normal brain function led to novel investigations during development and aging that suggested functional interactions between specific systems. In 1980, his pivotal publication in Science demonstrated that fetal neurons could be transplanted to the brain of a genetic mutant rat that that was incapable of producing vasopressin and that grafted fetal neurons could survive, integrate with the host brain and restore a lost neural function. This lead to new and continuing studies on the potential for fetal dopamine neurons to restore motor activity in a primate model of Parkinson’s disease. His proof of principle findings led to the first clinical trials in parkinson patients and in recent years have been extended to incorporate human neural stem cells in the experimental protocols. Professor Sladek continues his exploration of the ability of the primate brain to respond to various neural repair strategies including the potential for induction of neurogenesis in response to injury. His work has been supported continuously by NIH, NSF and several foundations since 1974. Dr. Sladek is the founding President of the American Society for Neural Therapy and Repair, has presented his work at over 350 invited meetings and seminars and is Editor-in-Chief Emeritus of the journal, Experimental Neurology.
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.
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.
Ms. Tice's research interests include psychosis in Parkinson's Disease, caregiver support in chronic disease progression, the role of CBD in pain management, and long term effects of ICU delirium on cognition and depression.
Dr. Tsai is interested in the regulation of sleep and the biological effects of sleep. The interaction between sleep disorders and neurological diseases, such as that between sleep apnea and stroke, RBD and neurodegenerative disorders, and RLS and movement disorders, is an area of particular importance.
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 in the CNS. Major current projects include: (1) Identifying differences in patterns of gene expression in the brain and the cognate signaling pathways induced by distinct neurotropic viruses, including reoviruses and flaviviruses (West Nile and Japanese encephalitis virus), in an effort to identify novel therapeutic targets for antiviral therapy; (2) Investigating the neuroinflammatory responses to CNS viral infections, including the activation of astrocytes, microglia and chemokine/cytokine production in experimental models utilizing mice and ex vivo brain and spinal cord slice cultures; and (3) Studying the mechanism of virus-induced CNS apoptosis, including mitochondrial and cell-death mediated pathways, and the impact of modulating these pathways on CNS injury and neuronal death.
Dr. Vaughan has completed fellowship training in Movement Disorders and in Hospice/Palliative Medicine and holds a Master of Clinical Research (M.S.). She has participated in multiple clinical research studies as co-investigator, site-PI, and has served as Clinical Monitor for several multi-center clinical trials through the Huntington’s Study Group. At present she is most interested in: the optimization of multi-disciplinary care models for those with advanced and end-stage neurologic disease; strategies to improve quality of life for those with advanced neurologic disease and their families; the development of non-pharmacologic and pharmacologic interventions for management of advanced symptoms of parkinsonism, Huntington disease, and other movement disorders; and integration of tele-medicine as a means of outreach for those with advanced neurologic disease.
Dr. Vollmer is the Director of Neurosciences Clinical Research. He is currently involved as Principle Investigator or Sub Investigator on approximately 30 clinical studies in multiples sclerosis at the University of Colorado. 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 using volumetric MRI and biomarkers as key outcome assessments. He also collaborates with several basic science laboratories on mechanism of action of newer MS therapies, and is working in collaboration to develop a vaccine approach to MS that involves inducing regulatory B lymphocytes that target CNS antigens. 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 internationally.
Ms. Walczyk is interested in research that focuses on the etiology, prevention, and treatment of neuroimmunological diseases such as Multiple Sclerosis and Neuromyelitis Optica spectrum disorders. She is also interested in the teaching and training of Advanced Practice Providers in subspecialty practices such as Neurology.
Ms. Wall's research interests include immunotherapies for multiple sclerosis (MS) patients and quality of life in patients with demyelinating diseases.
Dr. West’s research interests cover multiple areas, including medical education, inpatient medicine and multiple sclerosis (MS). His primary interest is in medical/clinical education, particularly for residents and fellows, and includes methods of bedside teaching, curriculum development and effective feedback. He has also been involved in inpatient studies of acute treatment of stroke, secondary stroke prevention, and quality improvement initiatives in hospitalized neurology patients. His other area of interest is in optimizing treatment in patients with MS.
Dr. Wicklund has been involved in clinical and translational research of neuromuscular disorders with specific emphasis on muscle diseases, including gene therapies for muscular dystrophies. His research includes persons of all ages, both adults and children.
I am interested in epilepsy as a whole, and the improvement in the quality of life of our patients. I am also very interested in more effective treatments for those with non-epileptic seizures and improving their prognosis through better mental health services.
Dr. Woodcock directs clinical research projects in dementia including medication trials in Alzheimer’s disease, cognitive and functional deficits in adults with Down syndrome, and assessment and management of behavioral syndromes in dementia.
Andrew Bubak, PhD
Laboratory of Maria Nagel, MD
Varicella zoster virus (VZV) is an exclusively human neurotropic virus that causes chickenpox (varicella) on primary infection after which virus establishes latency in neurons in the cranial nerve, dorsal root and autonomic ganglia along the entire neuraxis. With a decline in VZV-specific cell-mediated immunity such as seen in the elderly and immunocompromised individuals, VZV reactivates from one or more ganglia and typically produces zoster, which can be complicated by persistent dermatomal distribution pain (postherpetic neuralgia; PHN). I am interested in the neurochemical mechanisms mediating PHN at the junction of the peripheral and central nervous systems, with the hope of discovering novel targets for pain therapy. An additional interest includes developing RNAi based therapies for the prevention and treatment of viral infections.
James Eric Hassell, Jr., PhD
Laboratory of Maria Nagel, MD
Dr. Hassell completed his Ph.D. in Integrative Physiology/Neuroscience at the University of Colorado Boulder in 2019. His work in the Nagel lab focuses on behavioral changes and multi-organ changes that accompany varicella zoster virus (VZV) infection.
Michael Rudy, PhD
Laboratory of Kenneth Tyler, MD
Dr. Rudy conducted his graduate and postdoctoral research at the University of Rochester. Enterovirus D68 (EV-D68) is an emerging pathogen which causes a biennial respiratory disease and is associated with a rapid-onset muscle-weakness and limb paralysis in children (termed “acute flaccid myelitis”). The number of confirmed EVD-68 cases has increased markedly since its discovery, with 9 documented cases between 1962-2005; 699 documented cases between 2005-2010; and thousands of cases since 2014. It is not known whether the increased virulence of EV-D68 is due to a change in the virus or a change in population immunity. Density gradient centrifugation of three modern EV-D68 strains (US/MO/14-18947; US/CA/14-4231; US/IL/14-18952) plus an ancestral strain (Fermon) identified three distinct densities of infectious virus. Electron microscopy shows two different densities of naked particles and a third, previously unrecognized, membrane-associated form of the virus. Over 30% of the total infectivity of modern strains is associated with naked viral particles found at a density between 1.170g/cm3 and 1.210g/cm3, while less than 1% of the infectivity of Fermon is found in this density range, suggesting that particles with this density may account for differences in virulence between the modern and ancestral strains. Modern strains also show a second peak of infectivity at a density of 1.240g/cm3, while the ancestral Fermon strain shows only a single peak of infectivity at 1.272g/cm3. The membrane-associated form of the virus (density 1.070g/cm3 – 1.165g/cm3) appears to be present, in variable amounts, in all strains. It is infectious, sensitive to non-ionic detergent, and is positive for both CD63 and CD81, suggesting that the virus is associating with exosomes.