Neurodegenerative diseases are characterized clinically by their insidious onset and chronic progression. Particular parts of the brain, spinal cord, or peripheral nerves functionally fail and the neurons of the dysfunctional region die. Neuroanatomically localizable functional impairment and neurodegeneration associate with recognizable syndromes that are ideally distinct, although in clinical and even neuropathologic practice substantial syndromic overlap exists. Neurodegenerative disease clinical syndromes are often categorized by whether they initially affect cognition, movement, strength, coordination, sensation, or autonomic control. Frequently, however, patients will present with symptoms and signs referable to more than one system. Either involvement of several systems can occur concomitantly, or else by the time the patient has functionally declined enough to seek medical attention multiple systems have become involved. Diagnosing neurodegenerative diseases can prove particularly intimidating to clinicians, because many times the diagnosis cannot be critically “confirmed” by a simple test.
Neurodegenerative diseases are complicated on other levels. While the term “neurodegenerative” implies it is the loss of neurons that cause disease, it is possible neuronal demise is merely the final stage of a preceding period of neuron dysfunction. It is difficult to know whether clinical decline associates with actual neuron loss, or with a period of neuron dysfunction that precedes neuron loss. Also, particular neurodegenerative diseases are etiologically heterogeneous. The manifestations of human nervous system failure, not surprisingly, are limited. This brings up some very real questions of lumping versus splitting.
In addition to syndromically defining neurodegenerative diseases by what neuroanatomical system is involved, these disorders are broken down along other clinical lines. Early (childhood, young adulthood, or middle aged adulthood) versus late (old age) onset is an important distinction. Some clinically similar neurodegenerative diseases are sub-categorized by their age of onset, despite the fact at the molecular level different forms of a particular disease may have very little in common. Sporadic onset versus Mendelian inheritance constitutes another important distinction, and many named neurodegenerative diseases have both sporadic (Mendelian inheritance is not recognizable) and Mendelian subtypes.
A brief list of well characterized neurodegenerative diseases. This list is not inclusive, and diseases can present in ways in which they have not been listed. ANS/PNS=autonomic nervous system/peripheral nervous system.
| Cognition | Movement | Strength | Coordination | PNS/ANS | Myelin |
|---|---|---|---|---|---|
Alzheimer’s disease Frontotemporal dementia Dementia with Lewy bodies Corticobasal degeneration Progressive supranuclear palsy Prion disorders |
Parkinson’s disease Frontotemporal dementia Dementia with Lewy bodies Corticobasal degeneration Progressive supranuclear palsy Huntington’s disease |
Amyotrophic lateral sclerosis Frontotemporal dementia Hereditary spastic paraparesis |
Spinocerebellar atrophies Friedreich’s ataxia Prion disorders |
Amyloidoses Friedreich’s ataxia Metabolic (diabetes) related Toxin related |
Multiple Sclerosis Charcot Marie Tooth |
The Neurodegenerative Disorders Division has these subdivisions:
Degenerative disorders of the brain can present as memory loss, personality change, problems with movement, weakness, or poor balance.
These neurodegenerative diseases can present with memory loss or personality change: Alzheimer’s disease, Frontotemporal Dementias, Dementia with Lewy Bodies, Prion diseases.
These neurodegenerative diseases can present as problems with movements: Parkinson’s disease, Huntington’s disease, Progressive Supranuclear Palsy, Corticobasal Degeneration, Mutiple System Atrophy.
These neurodegenerative diseases can present as weakness: amyotrophic lateral sclerosis, inclusion body myositis, degenerative myopathies.
These neurodegenerative diseases can present as poor balance: the spinocerebellar atrophies.
Degenerative disorders of nerves can present as problems with sensation, strength, pain, or autonomic control
Disorders of the peripheral nerves include diabetic neuropathy, other metabolic neuropathies, endocrine neuropathies, orthostatic hypotension
Disorders of Myelin include multiple sclerosis, Charcot-Marie-Tooth disease
I am currently working at the Department of Pharmacology and Toxicology of School of Pharmacy as a Research Assistant Professor. I also have affiliation with Center for Neurobiology Research at the Higuchi Biosciences Center. I have earned my undergraduate degree in chemistry and my master’s degree in clinical biochemistry from Ataturk University-Turkey. I was awarded UNESCO Fellowship to study abroad and I earned my PhD degree in biochemistry from Attila Joseph Science University-Hungary. I was awarded university docent (equivalent to associate professor) title by the High Education Council-Turkey in the field of biochemistry in 1998. I have completed my postdoctoral trainings at the University of Missouri-Kansas City, the University of Kansas Medical Center, and the University of Kansas in the field of neurochemistry, cell and developmental biology, and molecular biology. I have been awarded UNESCO fellowship, and travel awards for participating the symposiums, and scholarship to attend the molecular biology of aging in Marine Biology Laboratories.
My research interests cover molecular biology of aging and aging related neurodegenerative diseases. I have worked and published on certain key proteins in central nervous system that undergo oxidative modifications during aging. I have recently developed an interest to study protein-protein interactions in ALS disease.
Dr. Heather Anderson is a graduate of Oklahoma State University with a degree in Biochemistry. She is a graduate of the University of Kansas School of Medicine. During her last year of neurology residency training at the University of Kansas Medical Center, she served as Chief Resident. She has also completed a Neurophysiology Fellowship at the University of Kansas Medical Center. Dr. Anderson is board certified for the American Board of Psychiatry and Neurology. She is an Assistant Professor in the Department of Neurology at the University of Kansas Medical Center, Medical Student Clerkship Director for the medical school, chair of the Medical Student Education Committee, and is a member of the Curriculum Planning Committee at the University of Kansas Medical Center and School of Medicine. A native Kansan, Dr. Anderson is a member of the American Academy of Neurology.
Dr. Anderson is a neurologist in the Alzheimer and Memory Center who evaluates and cares for patients with memory disorders. Her research concentration is in Alzheimer’s disease and brain aging. Dr. Anderson serves as the Principal Investigator for the Alzheimer Disease Exercise Program Trial (ADEPT) and as a sub-investigator in the Brain Aging Project and in the Alzheimer’s Disease Clinical Research Program.
Andrei B. Belousov, Ph.D., Associate Professor. Received an M.S. degree from Kazan State University (1987, Russia) and a Ph.D. degree from M.V. Lomonosov Moscow State University (1992, Russia). Completed postdoctoral trainings in McGill University (1992-1993; Canada) and Stanford University (1994-1998; California). Received a number of awards, including research awards from National Alliance for Research on Schizophrenia and Depression, Louisiana Board of Regents Support Fund, American Heart Association, National Institutes of Health, National Science Foundation and others.
His research is focused on changes in neuron-to-neuron communication during development, stroke and traumatic brain injury. Specifically, his research interests include: 1) Glutamate-dependent neuronal plasticity and the regulation of cholinergic phenotype in developing and mature CNS neurons; 2) Activity-dependent homeostatic plasticity in the CNS neurons; 3) The cellular and molecular mechanisms of regulation of electrical synapses (gap junctions) during development, traumatic brain injury and stroke.
Dr. Choi received her Ph.D. in Biophysics at the University of Minnesota. After her postdoctoral training at the Center for Magnetic Resonance Research at the University of Minnesota, she continued her research in the Department of Medical Physics at the Nathan Kline Institute as a senior research scientist and also served as a Section Leader for MR Spectroscopy at the Center for Advanced Brain Imaging. She serves as a reviewer of many journals including Neurobiology of Aging, Biological Psychiatry, Neurochemical Research and Journal of Psychiatry and Neuroscience. She also serves as a volume editor of Handbook of Neurochemistry and Molecular Neurobiology and an Editorial board member of “Frontiers in Neuroenergetics”. She has received various awards from scientific societies including International Society for Magnetic Resonance in Medicine, International Society for Neurochemistry and American Federation for Aging Research.
Dr. Choi’s research focus involves the basic mechanisms of brain energy metabolism in diabetes, aging, neurodegeneration and neurological disorders using noninvasive neuroimaging techniques. In vivo magnetic resonance (MR) techniques provide a unique opportunity to investigate brain physiology and pathophysiology in a completely noninvasive manner. In particular MR spectroscopy allows detection of critically important chemicals in the brain such as glucose (the obligatory energy substrate), glutamate (the major excitatory neurotransmitter), γ-aminobutyric acid (GABA, the major inhibitory neurotransmitter) and antioxidants such as glutathione (GSH) and vitamin C.
Diabetic peripheral neuropathy (DPN) results from the degeneration of nerves that transmit sensations from the legs and arms. Schwann cells are specialized cells that closely associate with many nerves and also undergo profound changes in DPN. Schwann cells are necessary to form the myelin membrane that is present on many peripheral nerves and the loss of this myelin membrane is a common characteristic of human diabetic neuropathy. Identifying molecular mechanisms that may prevent demyelination or enhance remyelination are therefore good targets for therapeutic interventions in human DPN. To this end, we are using a cell culture model of myelinated nerve to identify new molecular targets that can prevent demyelination.
Neuregulins are critical growth factors that activate a cell receptor called Erb B2 on Schwann cells. Although the activity of Erb B2 is low in Schwann cells from normal nerves, recent data suggests that pathologic activation of Erb B2 by neuregulins may induce demyelination of nerve and contribute to the development of peripheral neuropathies. Based on evidence from our lab, we have shown that hyperglycemia can increase the activity of Erb B2 receptors and enhance nerve demyelination. Once focus in the lab is to determine if inhibiting Erb B2 receptors may be beneficial in treating DPN.
In attempts to identify other compounds that prevent this degeneration, we have discovered a novel small molecule inhibitor of a protein called heat shock protein 90 that prevents neuregulin-induced demyelination. This drug was developed at the University of Kansas and is called KU-32. Preliminary data indicates that KU-32 is a non-toxic, orally bioavailable compound that has neuroprotective effects against neuronal cell death. Therefore, the goals of our research are to determine the molecular mechanism by which KU-32 prevents neuregulin-induced demyelination in our cell culture model. Additionally, we will assess the effectiveness of KU-32 in reversing the physiological progression of DPN in diabetic mice. These physiological studies will permit us to determine if KU-32 is suitable for further pre-clinical development. When completed, we anticipate that integrating the results from the biochemical and physiological studies will identify if targeting heat shock protein 90 offers a potential therapeutic approach toward treating DPN.
Dr. Robb Krumlauf is the Scientific Director of the Stowers Institute. He holds academic appointments as Professor in the University of Kansas Neuroscience Graduate Program and the University of Kansas Medical School, Department of Anatomy and Cell Biology. Dr. Krumlauf received his B.E. in chemical engineering from Vanderbilt University (‘70) and worked as the Chief Chemical Engineer at Stokley Van Camp before earning his Ph.D. in Developmental Biology from Ohio State University (’79). Dr. Krumlauf did postdoctoral training at the Beatson Institute for Cancer Research in Glasgow, Scotland and at the Institute for Cancer Research in Philadelphia, PA. For 16 years he ran a research group and served as the Head of the Division of Developmental Neurobiology at the MRC National Institute for Medical Research in London, UK. In 2000 he joined the Stowers Institute. He is an elected fellow of the American Academy of Arts and Sciences, the American Association for the Advancement of Science, the European Molecular Biology Organization, and the British Academy of Medical Sciences. Dr. Krumlauf sits on the Board of Directors and Scientific Advisory Boards of many national and international institutions and societies. He serves as the Editor-In-Chief of the journal Developmental Biology, is a member of the Editorial Board of 10 other peer-reviewed journals and is member of review panels for many external funding organizations, including the National Institutes of Health and Howard Hughes Medical Institute.
Dr. Krumlauf’s research focuses on understanding the conserved molecular and cellular pathways that control brain development and formation of the basic body plan. A fundamental goal of the team is to understand what imposes the unique identity of different regions of the developing brain. His research has lead to the identification of families of regulatory genes that control patterning and differentiation of the nervous system during normal development and how processes are altered or affected in human diseases. By using comparative studies in a number of vertebrate model systems his work addresses fundamental problems in neurobiology which have relevance to regenerative medicine and in designing strategies for the diagnosis and treatment of neurological disorders.
Dr. Lee received his Ph.D. in Biophysical Sciences and Medical Physics from University of Minnesota. His research topic was the physiological bases of functional magnetic resonance image (MRI) signals. Dr. Lee completed his postdoctoral training at the Center for Magnetic Resonance Research in University of Minnesota. His research continued at the Nathan Kline Institute as a senior research scientist and focused on the early detection of neurodegenerative diseases including Alzheimer’s disease using MRI by visualizing ß-amyloid plaques in the brain. Dr. Lee is a reviewer of many journals including Behavioral Brain Research, Radiology and Magnetic Resonance in Medicine. He also served as a grant reviewer of Medical Research Council (MRC), UK.
Dr. Lee’s current research interests include the characterization and understanding of biological processes in the living brain at the cellular and molecular level using magnetic resonance. Dr. Lee also works on the development of novel MR imaging techniques for early diagnosis and identification of changes in functional and physiological aspects of neurodegenerative diseases during the disease progression. Recently he has developed an MR technique to quantify axonal transport deficits in the Alzheimer’s disease.
University of California at Berkeley – B.A. Biology
Albert Einstein College of Medicine – M.A. Pathology
Albert Einstein College of Medicine – Ph.D. Pathology
UCLA – Postdoctoral Fellow in Neurosciences
University of Kansas Medical Center – Professor of Molecular and Integrative Physiology
We are interested in advancing the understanding of the disease processes in two disorders of myelin: multiple sclerosis and Krabbe’s disease. Myelin is essential for the normal communication between different areas of the nervous system and a loss of myelin can lead to sensory, motor and/or cognitive impairment. A greater knowledge of disease mechanisms can be used to identify new therapeutic targets. Thus, we also investigate therapeutic intervention strategies.
We take a team approach to our studies. Dr. Sharon Lynch is the Director of the Multiple Sclerosis Clinic at KUMC. Dr. Lynch screens patients for MS and we utilize blood from these subjects to analyze peripheral blood lymphocytes. Dr. Joyce Slusser is the Director of the Flow Cytometry Core at KUMC. Dr. Slusser oversees the analysis of the lymphocyte data. Dr. Stephen Benedict is an Associate Professor of Molecular Biosciences at KU. Dr. Benedict is an immunologist and he provides valuable guidance regarding the design and interpretation of studies on lymphocytes.
In addition, we utilize animal models of multiple sclerosis and Krabbe’s disease. These models enable us to explore new components of the pathogenic processes as well as to test new ideas for therapeutic intervention. Our goal is to identify new therapeutic strategies for these disorders.
Dr. Kelly Lyons is a Research Associate Professor of Neurology and Director of Research and Education for the Parkinson’s Disease and Movement Disorder Center at the University of Kansas Medical Center. She received her Ph.D. in Experimental and Cognitive Psychology with a concentration in Gerontology from the University of Kansas in 1993. She completed a fellowship in neurodegenerative disorders at the Parkinson's Disease and Movement Disorder Center at the University of Kansas Medical Center. She stayed at the University of Kansas Medical Center, Department of Neurology as a faculty member until 2000 at which time she moved to the University of Miami in Miami, Florida as an Assistant Professor and Director of Research of the Parkinson’s Disease Center. She worked closely with the National Parkinson Foundation also in Miami. She returned to the University of Kansas Medical Center in 2003.
Dr. Lyons' research focuses on Parkinson's disease and essential tremor. She has over 200 articles and presentations on these topics. She is a co-editor of the Handbook of Parkinson's disease, 3rd and 4th editions, Therapy of Parkinson’s Disease, 3rd edition and Essential Tremor and Other Tremor Disorders. Dr. Lyons is a member of the Education Committee of the Movement Disorder Society, Editor and Chair of the Journal CME committee, Member of the Website Committee and Member of the Website Committee Editorial Board of the Movement Disorder Society, Secretary and Treasurer of the Tremor Research Group, and President of the International Essential Tremor Foundation.
Dr. Michaelis received his M.D. degree in 1969 from St. Louis University School of Medicine, followed by an internship in surgery at Downstate Medical Center in Brooklyn N.Y. In 1970, he joined the Public Health Service, Addiction Research Center and Hospital in Lexington, KY. In 1971, he joined the department of Physiology and Biophysics at the University of Kentucky in Lexington, as a graduate student, where he initiated his research efforts on the glutamate neurotransmitter system in brain neurons. Dr. Michaelis performed his research under the sponsorship of a Special Doctoral Fellowship from NINCDS. He joined the University of Kansas in 1973 as an Assistant Professor of Human Development and of Biochemistry. Dr. Michaelis is currently a University Distinguished Professor of Pharmacology and Toxicology and the Director of the Higuchi Biosciences Center.
Across the years at the University of Kansas, Dr. Michaelis has maintained an active research program in neurochemistry, molecular neurobiology and neuropharmacology, and he has had continued grant support from the US Federal Agencies, the State of Kansas and private industry. Dr. Michaelis has received several awards for his research including the Alumnus Merit Award from St. Louis University School of Medicine, the Dolph Simons Sr. Award for Research Excellence at the University of Kansas, and a MERIT Award from the National Institute on Alcohol Abuse and Alcoholism. Dr. Michaelis has been a member and the chair of National Institutes of Health grant review boards, a member of the Board of Oread Laboratories Corporation and of the Institute for Studies on Aging, the Alzheimer Drug Discovery Foundation, the Dystonia Medical Research Foundation, and a member of the Scientific Advisory Boards of Promega Corporation and Aventis Pharmaceutical Company. Research in his laboratory is currently focused on the mammalian glutamate neurotransmitter system and its role in alcoholism, oxidative stress, age-associated neurodegeneration, and Alzheimer’s Disease. In this research effort, biochemical isolation of proteins, gene cloning, heterologous expression of gene products, immunochemical, transgenic and genomic approaches are being pursued.
After graduation from the University of Kansas School of Medicine, Dr. Newell received postgraduate training in anatomic pathology at the University of Colorado Medical Center, Denver, followed by neuropathology fellowship in the C.S. Kubik Laboratory for Neuropathology at the Massachusetts General Hospital, Boston. Following this, she studied in the MGH laboratories of Jean Paul Vonsattel and Brad Hyman, learning techniques and approaches useful in the research of human neurodegenerative disease, including Alzheimer disease, dementia with Lewy bodies, and Huntington disease.
In August 2002, Dr. Newell joined the Department of Pathology and Laboratory Medicine at the University of Kansas Medical Center where she is a staff neuropathologist and Director of Neurosciences. Dr. Newell is certified by the American Board of Pathology in both anatomic pathology and neuropathology.
Russell Swerdlow, MD is the Director of the Neurodegenerative Disorders Division and a Professor in the Departments of Neurology and Molecular and Integrative Physiology. After receiving his undergraduate and doctor of medicine degrees from New York University, he trained as a neurologist and cognitive disorders subspecialist at the University of Virginia. In addition to his clinical side, Dr. Swerdlow is a laboratory-based neuroscientist who is internationally known for his work on mitochondrial dysfunction in neurodegenerative diseases. National level recognition includes the S. Weir Mitchell Award from the American Academy of Neurology, a Cotzias Fellowship from the American Parkinson’s Disease Association, research grants from the National Institutes of Health, and membership on NIH and Veteran’s Administration Study Sections. Before joining KUMC in 2007, Dr. Swerdlow chaired the Alzheimer’s Disease and Related Disorders Commission of the Commonwealth of Virginia. He currently serves as the Research Committee Chair for CurePSP.
Dr. Swerdlow’s laboratory studies the interaction between genes and cell energy metabolism, the molecular consequences of altered cell energy metabolism, and strategies for repairing defective energy metabolism. The goals of this work are to better understand the molecular mechanisms that underlie brain aging and neurodegeneration, and to develop treatments for neurodegenerative diseases that have impaired energy metabolism including Alzheimer’s disease, Parkinson’s disease, amyotrophic lateral sclerosis, and Huntington’s disease. This work is largely funded through grants from the National Institutes of Health and from generous contributions from the community.
Dr. Wright received his Ph.D. from the University of Kentucky in 1992. He completed a postdoctoral fellowship (1993-1997) in the Department of Neurology at Washington University in St. Louis Missouri. He is an Associate Professor in the Department of Anatomy and Cell Biology. Dr. Wright began his career studying neural pathways that control pituitary function and reproduction. His postdoctoral work focused on the development of the nervous system and factors that dictate the survival of neurons during critical developmental stages. Dr. Wright serves on numerous review panels for the National Institutes of Health as well as the Juvenile Diabetes Research Foundation (JDRF) Medical Science Review Committee. He has served as a mentor for a large number of PhD and MD/PhD students, and has published numerous papers related to the function of the nervous system in various disease settings. His work is currently funded by 2 grants from the National Institutes of Health and a research grant from the JDRF. Dr. Wright has also received a number of teaching awards from the Kansas University Medical Center, including the Student Voice Award, the Chancellor's Distinguished Teaching Award and the Peter T. Bohan Teaching Professorship Award.
The focus of Dr. Wright's research is to understand how diabetes damages peripheral nerves and how treatments may be developed to treat the neural symptoms affecting patients with diabetes. The majority of patients with diabetes develop insensate (loss of sensation) symptoms, whereas a smaller subset of patients can develop debilitating pain. The mechanisms by which some patients develop insensate neuropathy versus painful neuropathy are still a mystery. Many variables play a role in the development of these diverse symptoms, including reduced neurotrophic supply, abnormal insulin support, and oxidative stress mediated through advanced glycation endproduct (AGE) formation. In addition, many patients with diabetes suffer from large fiber dysfunction, making coordinated movements difficult and placing them at risk for falls. Dr. Wright has studies that address the mechanisms that lead to large fiber dysfunction and is testing the ability of exercise to improve peripheral nerve-mediated control of gait and balance.
Dr. Ron Yu holds a Ph.D. in Cellular, Molecular and Biophysical studies from Columbia University and B.Sc. degrees in Biological Sciences and Biotechnology and in Solid State Physics from Tsinghua University in Beijing, China. He did his postdoctoral research in the laboratory of Dr. Richard Axel, a winner of the 2004 Nobel Prize for Physiology or Medicine, at Columbia University. At Columbia University, Dr. Yu held a National Institutes of Health Mentored Research Scientist Award from the National Institute of Mental Health. He joined the Stowers Institute and became a member of the faculty of Department of Anatomy and Cell Biology at KUMC in 2005. He is the winner of 2008 of the Hudson Prize and holds a $2 million grant from the NIH.
Dr. Yu’s work deals with the mechanisms of sensory information processing in the brain — especially as it relates to the sense of smell. He studies the neural circuits and their physiological functions in the mouse olfactory and vomeronasal systems to reveal how the nervous system detects, parses, and integrates sensory information and generates meaningful behaviors. This line of work will reveal the general principles that govern the proper formation and functioning of neural circuitry in the human brain that underlies complex cognitive and social behaviors. Proper formation of the neural circuitry and seamless processing of sensory information are essential for mental health. Alterations in either can lead to devastating psychiatric and neurological diseases such as schizophrenia, autism, Parkinson's disease, and Alzheimer's disease. The molecular and cellular mechanism behind these important functions of the brain will lead to a better understanding of how the brain works and to possible treatments for neurological diseases.
Diabetic peripheral neuropathy (DPN) results from the degeneration of nerves that transmit sensations from the legs and arms. Schwann cells are specialized cells that closely associate with many nerves and also undergo profound changes in DPN. Schwann cells are necessary to form the myelin membrane that is present on many peripheral nerves and the loss of this myelin membrane is a common characteristic of human diabetic neuropathy. Identifying molecular mechanisms that may prevent demyelination or enhance remyelination are therefore good targets for therapeutic interventions in human DPN. To this end, we are using a cell culture model of myelinated nerve to identify new molecular targets that can prevent demyelination.
Neuregulins are critical growth factors that activate a cell receptor called Erb B2 on Schwann cells. Although the activity of Erb B2 is low in Schwann cells from normal nerves, recent data suggests that pathologic activation of Erb B2 by neuregulins may induce demyelination of nerve and contribute to the development of peripheral neuropathies. Based on evidence from our lab, we have shown that hyperglycemia can increase the activity of Erb B2 receptors and enhance nerve demyelination. Once focus in the lab is to determine if inhibiting Erb B2 receptors may be beneficial in treating DPN.
In attempts to identify other compounds that prevent this degeneration, we have discovered a novel small molecule inhibitor of a protein called heat shock protein 90 that prevents neuregulin-induced demyelination. This drug was developed at the University of Kansas and is called KU-32. Preliminary data indicates that KU-32 is a non-toxic, orally bioavailable compound that has neuroprotective effects against neuronal cell death. Therefore, the goals of our research are to determine the molecular mechanism by which KU-32 prevents neuregulin-induced demyelination in our cell culture model. Additionally, we will assess the effectiveness of KU-32 in reversing the physiological progression of DPN in diabetic mice. These physiological studies will permit us to determine if KU-32 is suitable for further pre-clinical development. When completed, we anticipate that integrating the results from the biochemical and physiological studies will identify if targeting heat shock protein 90 offers a potential therapeutic approach toward treating DPN.
Dr. Robb Krumlauf is the Scientific Director of the Stowers Institute. He holds academic appointments as Professor in the University of Kansas Neuroscience Graduate Program and the University of Kansas Medical School, Department of Anatomy and Cell Biology. Dr. Krumlauf received his B.E. in chemical engineering from Vanderbilt University (‘70) and worked as the Chief Chemical Engineer at Stokley Van Camp before earning his Ph.D. in Developmental Biology from Ohio State University (’79). Dr. Krumlauf did postdoctoral training at the Beatson Institute for Cancer Research in Glasgow, Scotland and at the Institute for Cancer Research in Philadelphia, PA. For 16 years he ran a research group and served as the Head of the Division of Developmental Neurobiology at the MRC National Institute for Medical Research in London, UK. In 2000 he joined the Stowers Institute. He is an elected fellow of the American Academy of Arts and Sciences, the American Association for the Advancement of Science, the European Molecular Biology Organization, and the British Academy of Medical Sciences. Dr. Krumlauf sits on the Board of Directors and Scientific Advisory Boards of many national and international institutions and societies. He serves as the Editor-In-Chief of the journal Developmental Biology, is a member of the Editorial Board of 10 other peer-reviewed journals and is member of review panels for many external funding organizations, including the National Institutes of Health and Howard Hughes Medical Institute.
Dr. Krumlauf’s research focuses on understanding the conserved molecular and cellular pathways that control brain development and formation of the basic body plan. A fundamental goal of the team is to understand what imposes the unique identity of different regions of the developing brain. His research has lead to the identification of families of regulatory genes that control patterning and differentiation of the nervous system during normal development and how processes are altered or affected in human diseases. By using comparative studies in a number of vertebrate model systems his work addresses fundamental problems in neurobiology which have relevance to regenerative medicine and in designing strategies for the diagnosis and treatment of neurological disorders.
Kenneth E. McCarson, Ph.D. is an Associate Professor In the Department of Pharmacology, Toxicology, and Therapeutics at the University of Kansas Medical Center. His long term Research focus is the regulation of G-protein coupled receptor expression and function by long-term neuronal activity. He received a Bachelor of Chemical Engineering (B.Ch.E.) degree from the Georgia Institute of Technology, Atlanta, Georgia, in 1984, followed by a Ph.D. in Pharmacology from the Medical College of Georgia, Augusta, Georgia (Major Advisor: Barry D. Goldstein, Ph.D.; Dissertation Title: Regulation of Substance P Levels and Release in the Dorsal Horn During Nociception) in 1991. From 1991-1995 he was a Postdoctoral Research Associate in the laboratory of James E. Krause, Ph.D.; Professor of Neurobiology at the Washington University School of Medicine, St. Louis, Missouri. He joined the KUMC faculty in 1995 and was promoted and tenured in 2001. He is currently the director of the Rodent Behavior Core Facility of the Biobehavioral Measurement Core (BMC) of the Kansas Intellectual and Developmental Disabilities Research Center (KIDDRC).
Dr. McCarson’s research program examines the role that various neurotransmitters and their receptors play in the regulation of sensory function, and particularly focuses of the role of a neurotransmitter called substance P and its receptors and how they contribute to chronic inflammatory pain. The way that the NK-1 receptors for substance P generate pain signals in the spinal cord is altered during persistent pain. Studying the expression, function and trafficking of these receptors will clarify how these changes lead to increased responsiveness to pain (hyperalgesia and allodynia) that are the hallmarks of chronic pain.
Areas of the brain involved in the regulation of mood are also affected by pain. Dr. McCarson’s studies have implicated changes in the birth and growth of new neurons in an area of the brain called the hippocampus as an important mood-regulating process that can be modified by environmental factors, including persistent pain. This line of research has shown that chronic pain activates cellular and molecular mechanisms that are linked to depression, and suggests that the depression common in chronic pain may have occur because of a fundamental neurological events initiated by pain.
Dr. McCarson’s research also investigates gender-related differences in pain sensation. Results from his laboratory have shown that estrogen modifies the expression of certain genes in pain pathways as well as in higher brain centers associated with the regulation of emotions and mood. Currently, the McCarson laboratory is exploring the sites and mechanisms of estrogens’ actions in the nervous system that may underlie how men and women sense pain differently, and how estrogens may worsen some common pain syndromes in women.
Peter G. Smith is Professor of Molecular and Integrative Physiology. He directs the Kansas Intellectual and Developmental Disabilities Research Center, the KU School of Medicine Microarray Facility, the Bioinformatics Core of the Kansas IDeA Network for Biomedical Research Excellence (K-INBRE), and is Associate Director for the statewide Kansas INBRE program. Born in Boston, Dr. Smith received a Bachelor of Arts from the University of New Hampshire and a PhD from Duke University in Physiology and Pharmacology in 1978. Following a fellowship in Pharmacology-Morphology from the Pharmaceutical Manufacturers Foundation and appointment as a Research Assistant Professor at Duke in 1982, he joined the University of Kansas Medical Center as an Associate Professor in 1987 and was promoted to professor in 1993.
Dr. Smith’s research concerns the peripheral nervous system and its role in health and disease. Ongoing programs include how nervous system plasticity contributes to sudden cardiac death, mechanisms of nerve degeneration, and how hormones affect the nervous system, particularly in regard to female pain syndromes. Dr. Smith’s research is funded by grants from the NIH and other sources totaling over $1 million annually. Professor Smith has authored nearly 90 original research papers and is a regular speaker at national and international conferences. He has chaired National Institutes of Health advisory committees and has received numerous awards including a Pharmacology-Morphology fellowship from the Pharmaceutical Manufacturer’s Association Foundation and an Established Investigatorship of the American Heart Association. He is recipient of many KU honors including the Research Investigator Award, a Kemper Fellowship for Excellence in Teaching, the 2006 Chancellors Club Research Award and the 2007 Chancellors Distinguished Teaching Award.
Dr. Smith’s program examines biological mechanisms leading to degeneration and loss of autonomic nerves. When these nerves degenerate, this can lead to disturbances in blood pressure and heart rate that can result in fainting, sexual function, swallowing, and a host of other symptoms. Dr. Smith’s program is directed at finding molecules that induce degeneration, understanding the cellular processes involved in nerve loss, and identifying molecules that can prevent or reverse this process.
Dr. Wright received his Ph.D. from the University of Kentucky in 1992. He completed a postdoctoral fellowship (1993-1997) in the Department of Neurology at Washington University in St. Louis Missouri. He is an Associate Professor in the Department of Anatomy and Cell Biology. Dr. Wright began his career studying neural pathways that control pituitary function and reproduction. His postdoctoral work focused on the development of the nervous system and factors that dictate the survival of neurons during critical developmental stages. Dr. Wright serves on numerous review panels for the National Institutes of Health as well as the Juvenile Diabetes Research Foundation (JDRF) Medical Science Review Committee. He has served as a mentor for a large number of PhD and MD/PhD students, and has published numerous papers related to the function of the nervous system in various disease settings. His work is currently funded by 2 grants from the National Institutes of Health and a research grant from the JDRF. Dr. Wright has also received a number of teaching awards from the Kansas University Medical Center, including the Student Voice Award, the Chancellor's Distinguished Teaching Award and the Peter T. Bohan Teaching Professorship Award.
The focus of Dr. Wright's research is to understand how diabetes damages peripheral nerves and how treatments may be developed to treat the neural symptoms affecting patients with diabetes. The majority of patients with diabetes develop insensate (loss of sensation) symptoms, whereas a smaller subset of patients can develop debilitating pain. The mechanisms by which some patients develop insensate neuropathy versus painful neuropathy are still a mystery. Many variables play a role in the development of these diverse symptoms, including reduced neurotrophic supply, abnormal insulin support, and oxidative stress mediated through advanced glycation endproduct (AGE) formation. In addition, many patients with diabetes suffer from large fiber dysfunction, making coordinated movements difficult and placing them at risk for falls. Dr. Wright has studies that address the mechanisms that lead to large fiber dysfunction and is testing the ability of exercise to improve peripheral nerve-mediated control of gait and balance.
Richard Barohn, MD
Merlin Butler, MD PhD
Mazen Dimachkie, MD
Steven Levine, PhD
Sharon Lynch, MD
Mamatha Pasnoor, MD
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The University of Kansas Medical Center