Forensic Psychiatry; Geriatric Psychiatry; Neurology; Psychiatry; Multiple Sclerosis; Alzheimer Disease / Memory Disorders; Neurodegenerative disorders; Neuropsychology
I direct two UBMD clinics: an outpatient neuropsychology practice at the Buffalo General Medical Center and an inpatient consultation service at the Erie County Medical Center. In addition, I provide services for patients at the Jacobs Multiple Sclerosis Center and the UB Alzheimer’s Disease and Memory Disorders Center. Our clinical mission is to provide compassionate, state-of-the-art care for patients and families affected by a wide range of neurological and psychiatric disorders. Our top-rate neuropsychological services are based on the integration of neurological, psychiatric and imaging findings and structured to meet the needs of our patients and their caregivers. Our neuropsychology service is dedicated to the teaching mission of UB. We support the departments of neurology and psychiatry as well as the rehabilitation services in the orthopaedic, occupational therapy and physical therapy divisions at our UB-affiliated hospitals. Students, residents and fellows have a rich learning experience with us and see a wide range of diseases such as personality disorder, malingering, depression, head trauma, concussion, multiple sclerosis (MS), stroke, dementia, epilepsy and pervasive developmental disorders. Medical students have the opportunity to work with both children and adults during didactics, and they may choose to focus on the evaluation of either patient population based on their clinical focus. My research mission is to employ behavioral psychometrics to understand how cerebral disease affects personality, cognition, and psychiatric stability. Two memory tests I developed, the Brief Visuospatial Memory Test Revised (BVMTR) and the Hopkins Verbal Learning Test Revised (HVLTR), are widely used in neuropsychology, especially in the areas of multiple sclerosis, head injury, and schizophrenia, and they are included in consensus panel test batteries for athlete concussions in the NHL and NFL. I work to develop new tests in order to understand more about the effect of cerebral injuries and disease. I also focus my research in multiple sclerosis (MS) and have conducted several studies on pharmacological treatments for cognitive function in MS patients. I have contributed in noteworthy studies as the lead author on a consensus battery for MS patients (the Minimal Assessment of Cognitive Function in MS), which is a gold standard in the literature, and as a major contributor to the idea that brain atrophy is the primary driver of cognitive impairment in MS, and in particular, deep gray matter atrophy. My major findings also include that personality changes can be assessed in MS patients, are more common in MS dementia, and relate to clinical outcomes, that self-report is not a valid indicator of neuropsychological status in MS, and that Symbol Digit Modalities Test is a reliable and valid marker for cognitive outcomes in clinical trials.
Endocrinology, Diabetes and Metabolism; Neurodegenerative disorders; Pathophysiology; Endocrinology; Molecular Basis of Disease
Dr. Browne’s research is focused primarily on the clinical biochemistry of oxidative stress (OS) in human health and disease. Specifically, his research focuses on mechanisms of oxidative lipid damage and the antioxidant roles of high-density lipoproteins (HDL. This research includes pure biomarker method development and validation employing primarily high pressure liquid chromatography (HPLC) and liquid chromatography-mass spectrometry (LC-MS) along with collaborative clinical studies of the role of oxidative stress in cancer, infertility and women’s health, and neurological disease. Current studies on-going in Dr. Browne’s laboratory include investigations of the role of HDL and PON1 in embryo morphology outcomes during in vitro fertilization (IVF), a study of the role of oxysterols in Multiple Sclerosis disease progression and investigations of the role of bioactive lipid mediators in response to air pollution.
Neurology; Neurodegenerative disorders; Pathophysiology; Apoptosis and cell death; Cytoskeleton and cell motility; Molecular and Cellular Biology; Molecular genetics; Neurobiology; Protein Folding; Gene Expression; Transcription and Translation; Signal Transduction; Toxicology and Xenobiotics
My research is aimed at finding the cause and a cure for Parkinson’s disease. Parkinson’s disease (PD) is defined by a characteristic set of locomotor symptoms (rest tremor, rigidity, bradykinesia and postural instability) that are believed to be caused by the selective loss of dopaminergic (DA) neurons in substantia nigra. The persistent difficulties in using animals to model this human disease suggest that human nigral dopaminergic neurons have certain vulnerabilities that are unique to our species. One of our unique features is the large size of the human brain (1350 grams on average) relative to the body. A single nigral dopaminergic neuron in a rat brain (2 grams) has a massive axon arbor with a total length of 45 centimeters. Assuming that all mammalian species share a similar brain wiring plan, we can estimate (using the cube root of brain weight) that a single human nigral dopaminergic neuron may have an axon with gigantic arborization that totals 4 meters. Another unique feature of our species is our strictly bipedal movement, which is affected by Parkinson’s disease, in contrast to the quadrupedal movement of almost all other mammalian species. The much more unstable bipedal movement may require more dopamine, which supports the neural computation necessary for movement. The landmark discovery of human induced pluripotent stem cells (iPSC) made it possible to generate patient-specific human midbrain dopaminergic neurons to study Parkinson’s disease. A key problem for dopaminergic neurons is the duality of dopamine as a signal required for neural computation and a toxin as its oxidation produces free radicals. Our study using iPSC-derived midbrain dopaminergic neurons from PD patients with parkin mutations and normal subjects shows that parkin sustains this necessary duality by maintaining the precision of the signal while suppressing the toxicity. Mutations of parkin cause increased spontaneous release of dopamine and reduced dopamine uptake, thereby disrupting the precision of dopaminergic transmission. On the other hand, transcription of monoamine oxidase is greatly increased when parkin is mutated. This markedly increases dopamine oxidation and oxidative stress. These phenomena have not been seen in parkin knockout mice, suggesting the usefulness of parkin-deficient iPSC-derived midbrain DA neurons as a cellular model for Parkinson’s disease. Currently, we are using iPS cells and induced DA neurons to expand our studies on parkin to idiopathic Parkinson’s disease. We are also utilizing the molecular targets identified in our studies to find small-molecule compounds that can mimic the beneficial functions of parkin. The availability of human midbrain DA neurons should significantly speed up the discovery of a cure for Parkinson’s disease.
Molecular and Cellular Biology; Neurodegenerative disorders; Transcription and Translation; Signal Transduction; Toxicology and Xenobiotics
My lab studies the receptor signaling mechanisms for a family of neurotrophic factors that includes ciliary neurotrophic factor (CNTF), leptin, interferon gamma, and cardiotrophin-1. These factors use the Jak/STAT pathway to regulate neuronal survival, development and response to trauma. Our interests are in how activity of the receptors and their pathway components are regulated. Currently this has focused on the impact of cellular oxidative stress on the inhibition of Jak tyrosine kinase activity. Increases in oxidative stress in neurons result in the blockade of not only CNTF family factor effects, but of many other cytokines that also use the Jak/STAT pathway for signaling such as interferons and interleukins. Non-nerve cells appear resistant to these effects of oxidative stress. Ongoing projects include testing the theory that environmental contaminants known to increase oxidative stress in cells may promote neurodegenerative diseases by inhibiting growth factor signaling. We have been studying the effects of certain heavy metals (cadmium & mercury) and pesticides (e.g. rotenone) on nerve cells in culture to determine the molecular basis for Jak inhibition. Another examines a possible role of oxidative stress in obesity. This study tests the hypothesis that the loss of the ability of the hormone leptin to regulate metabolism and appetite during obesity is a result of oxidative reactions that inhibit Jak-mediated signaling in the hypothalamus and other brain regions.
Children and Adults; General Neurology; Movement Disorders; Neurodegenerative disorders; Neurology; Parkinson's; Tourette's Syndrome
I received my medical degree from the University of Otago Medical School in New Zealand in 1977 and, following further advanced training in general medicine and Neurology was elected to Fellowship of the Royal Australasian College of Physicians in 1984. On completion of a Neurology residency and fellowship in Movement Disorders at the University of Rochester (1988), I joined the faculty of the Department of Neurology at the University at Buffalo. As a Clinical Professor at UB, I am engaged in patient care and the teaching of students, residents and fellows at the VA Medical Center. I also have a focused Movement Disorders clinic at the Brain and Spine Center (Williamsville, NY). My interests include not only disorders of voluntary movement but also the associated cognitive, behavioral and psychiatric dysfunction commonly accompanying such disorders. Accordingly, I conduct clinical studies in Movement Disorders not only with my Neurology and Neuroimaging colleagues at UB, but have also collaborated on clinical studies in Tourette syndrome with colleagues from the UB Department of Psychiatry, where I have a secondary appointment, and with members of the Division of Developmental and Behavioral Neurosciences. My publications include co-editing a textbook on “Frontal-Subcortical Circuits in Psychiatric and Neurological Disorders” (Guilford Press, 2001). I am an active member of the American Academy of Neurology, the Movement Disorders Society, the Tourette Syndrome Association, the American Neuropsychiatric Association, and the Royal Australasian College of Physicians.
Neurodegenerative disorders; Ion channel kinetics and structure; Membrane Transport (Ion Transport); Molecular Basis of Disease; Signal Transduction; Protein Function and Structure; Neuropharmacology
I focus my research on the activation mechanisms of fast neurotransmitter receptors. We seek to define the activation pathway, modulatory mechanisms and structure-function relationships of the N-methyl-D-aspartate (NMDA) receptor to better understand the roles played by this protein in the brain. NMDA receptors are the most abundant glutamate-stimulated, Ca2+-conducting ion channels in brain and spinal cord. They are the predominant molecular devices for controlling synaptic development and plasticity and govern memory and learning processes. Understanding the mechanisms that control their activity may lead to more effective strategies to treat neuropathies including stroke, neurodegenerative conditions, chronic pain and addiction as well as mental disorders such as schizophrenia and epilepsy.
Neurodegenerative disorders; Apoptosis and cell death; Membrane Transport (Ion Transport); Proteins and metalloenzymes; Signal Transduction; Toxicology and Xenobiotics
Dr. Jerome Roth‘s research interests over the past several years have focused on the mechanism of action of manganese in producing neuronal cell death. Manganese is an essential mineral that at high concentration acts as a neurotoxin which produces a Parkinson-like syndrome. Although the identified brain lesions associated with manganism differ from those of Parkinson’s disease, there is increasing evidence that chronic exposure to Mn correlates with increased susceptibility to develop Parkinsonism. Current studies are focused on characterizing the signal transduction pathways stimulated by manganese and to determine whether they also play a role in the toxic actions of this divalent cation. As part of this project we are also investigating the transport mechanisms by which manganese is taken up into cells. We have focused our studies on the divalent metal transporter (DMT1) and its role in the transport of manganese and other divalent cations. We are currently studying the transcriptional and post-translational factors that regulate its expression in vivo. Preliminary studies have linked DMT1 expression to the protein, parkin, mutations in which lead to early onset of Parkinson‘s disease. Whether other gene linked to Parkinsonism are also associate with development of manganism is the current focus of my research. Current studies in my laboratory focus on how other early and late genes associated with Parkinson’s disease can influence Mn toxicity as these studies will provide a basis for the comorbidity between manganism and Parkinson’s; the manipulation of this mechanism may therefore provide new prophylactic and/or management treatment options for Parkinson’s disease.
Multiple Sclerosis; Neurodegenerative disorders; Neuroimaging; Neurology; Neuroradiology - Radiology; Parkinson's; Radiological Physics; Radiology; Bioinformatics
Magnetic resonance imaging (MRI) is a unique technique for studying the human body since it is non-invasive, does not require ionizing radiation and offers a multiplicity of complementary tissue contrasts. My research seeks to explore the potential of MRI for clinical and pre-clinical imaging and to provide new and improved MRI technology. The goal of this endeavor is twofold: 1.) to contribute deeper insight into the etiology, pathogenesis and potential treatment of neurodegenerative diseases, and 2.) to give clinicians the ability to diagnose diseases earlier and monitor them more accurately. I am currently focusing on understanding MRI contrast mechanisms as well as on developing innovative imaging and reconstruction techniques that improve the sensitivity and specificity of MRI with respect to biophysical properties of brain tissue. Advancements in this field promise to have a substantial impact on our understanding of biophysical and morphological tissue alterations associated with neurological diseases and their treatment. We recently pioneered quantitative susceptibility mapping (QSM), a breakthrough in quantitative MRI. This technique allows for unique assessment of endogenous and exogenous magnetic particles in the human brain such as iron, calcium, myelin or contrast agents. The concept of QSM is fundamentally different from conventional MRI techniques as it involves solving for all imaging voxels simultaneously in large physically motivated equations, a so-called inverse problem. At the Buffalo Neuroimaging Analysis Center (BNAC), we use QSM to explore whether brain iron may serve as an early biomarker for diseases of the central nervous system such as multiple sclerosis and Parkinson’s disease. Other interesting applications of this technique we are investigating include differentiation between hemorrhages and calcifications, detection of demyelination and quantification of tissue oxygenation. I am fascinated by the synergies from combining physical expertise with high-level mathematical, numerical and engineering concepts to advance our understanding of the human brain. Consequently, my research activities are generally interdisciplinary and involve collaboration with clinicians, physicists, computer scientists, technicians and engineers. Student projects typically focus either on the application of techniques or on technical developments. Undergraduate, graduate and doctoral candidates from a variety of disciplines such as neuroscience, physics and mathematics work collaboratively in my lab.
Genomics and proteomics; Neurobiology; Neurodegenerative disorders
My lab investigates the molecular control of cell fate and homeostasis of resident stem and progenitor cells in the human brain. Using a combination of multicolor cell sorting techniques and whole genome analysis, we are characterizing the signaling pathways which regulate the formation and fate of human oligodendrocyte progenitor cells. We are testing the functional significance of these pathways using both pharmacological and viral methods in culture and animal-based models of myelination and demyelination.
Retina; Gene therapy; Neurodegenerative disorders; Pathophysiology; Protein Folding; Gene Expression; Signal Transduction
I am a Clinician Scientist working in the field of hereditary retinal and macular degenerations. I direct a regional referral service for these diseases at the Ross Eye Institute. My NIH- and VA-funded laboratory is focused on the development of gene-based therapeutics for hereditary retinal degenerations and common age-related macular degeneration.
Neurodegenerative disorders; Pathophysiology; Cytoskeleton and cell motility; Molecular Basis of Disease; Molecular and Cellular Biology; Neurobiology; Neuropharmacology; Signal Transduction
Synaptic Mechanisms of Mental Health and Disorders Our research goal is to understand the synaptic action of various neuromodulators that are linked to mental health and illness, including dopamine, stress hormones, and disease susceptibility genes. Specifically, we try to understand how these neuromodulators regulate glutamatergic and GABAergic transmission in prefrontal cortex (PFC), which is important for emotional and cognitive control under normal conditions. We also try to understand how the aberrant action of neuromodulators under pathological conditions leads to dysregulation of synaptic transmission in PFC, which is commonly implicated in brain disorders. The major techniques used in our studies include: • whole-cell patch-clamp recordings of synaptic currents, • viral-based in vivo gene transfer, • biochemical and immunocytochemical detection of synaptic proteins, • molecular analysis of genetic and epigenetic alterations, • chemogenetic manipulation of neuronal circuits, • behavioral assays. By integrating the multidisciplinary approaches, we have been investigating the unique and convergent actions of neuromodulators on postsynaptic glutamate and GABAA receptors, and their contributions to the pathogenesis of a variety of mental disorders, including ADHD, autism, schizophrenia, depression, PTSD and Alzheimer's disease.
Neurology; Neuroradiology - Radiology; Vascular and Interventional Radiology; Parkinson's; Multiple Sclerosis; Alzheimer Disease / Memory Disorders; Developmental Neurology; General Neurology; Neurodegenerative disorders; Neuroimaging
I direct the Buffalo Neuroimaging Analysis Center (BNAC) and have established the center as a world leader in performing quantitative MRI analysis in neurodegenerative disorders. I also direct the Translational Imaging Center at UB’s Clinical Translational Research Center (CTRC). I strive to extend the boundaries of current knowledge about neurological diseases and disorders through innovative imaging research techniques and the application of bioinformatics resources. My efforts are directed toward advancing technical, basic and translational research at UB which will, in turn, advance patient care. I have secured more than $30 million in research grants for collaborative research projects involving UB investigators as well as national and international collaborators. My research interests include structural and functional quantitative MRI analysis for humans and animals, including lesion/tumor identification and segmentation; perfusion and dynamic contrast-enhanced (DCE) mapping and quantification; fluid flow quantification; functional MRI analysis; diffusion tensor reconstruction and tractography; voxel-wise mapping and image-based group statistical analysis; longitudinal change analysis and tissue/pathology/structure volumetry. I study the application of these techniques in healthy individuals and in patients with various disease states such as multiple sclerosis (MS), stroke, Alzheimer’s disease, Parkinson’s disease, epilepsy, systemic lupus erythematosus and traumatic brain injury. I also concentrate on therapeutic interventions, including therapy directed toward assessing neuroprotective efforts in neurodegenerative disorders as well as the venous function, genetic and neuroepidemiology fields of these diseases. I direct the neurology resident research program. Over a period of two years, I guide third- and fourth-year medical residents through a rigorous assigned scientific research project that is a critical, required part of their training. In addition, I mentor and supervise undergraduate, master’s and doctoral students and MRI fellows. In this role, I help to educate these trainees on clinical MRI use as well as neuroimaging analysis. I also oversee students and fellows conducting research in neurological disorders. One of the most rewarding experiences in my career is helping young physicians and researchers start successful clinical or research careers.