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URMC Neurology Research
Scope of Research: Neurovirology, Neurotoxicology, Neurophysiology of Motor Control and Movement Disorders, Neurodegenerative Disorders, Clinical Trials, Genetics
Goals are to understand molecular, cellular, and neural systems mechanisms underlying neurological and developmental disorders of children and adults. Further goals are to understand the clinical characteristics, response to treatment, and public health aspects of complex neurological disorders of children and adults.
The roles of Platelet Activating Factor (PAF), a mediator of inflammation, on synaptic plasticity during Human Immunodeficiency Virus (HIV) infection. Development of novel biotechnology to study synaptic plasticity. Neural-immune signaling during synaptic inflammation. Molecular pathogenesis of astrocyte-neuronal signaling and identification of molecular targets for neuroprotection in HIV infection for a unique NIH-funded “bench-to-bedside” program project. (Gelbard)
Norman, J.P., Perry, S.W., Kasischke, K.A., Volsky, D.J. and Gelbard,
H.A. HIV-1 Tat Elicits Mitochondrial
Hyperpolarization and Respiratory Deficit, with Dysregulation of Complex IV and NAD(P)H Homeostasis in
Cortical Neurons. J. Immunol. 2007, 178(2):869-76.
Dewhurst, S., Maggirwar, S.B., Schifitto, G., Gendelman, H.E.
and Gelbard, H.A.. Glycogen synthase
kinase 3 beta (GSK-3b) as a therapeutic target in NeuroAIDS. J. Neuroimmune Pharm. 2007, 2:93-96.
Lu, S.-M. and Gelbard, H.A.. The phospholipid mediator platelet-activating
factor mediates striatal
synaptic facilitation. J. Neuroimmune Pharm. 2007, 2:194-201.
Sui, Z., Sniderhan, L.F., Schifitto, G., Phipps, R.P., Gelbard,
H.A., Dewhurst, S. and S.B. Maggirwar.
Functional synergy between CD40 ligand and HIV-1 Tat contributes to inflammation: implications in HIV-1
dementia. J. Immunol. 2007, 178(5):3226-3236.
DiCenzo, R., Peterson, D.R., Cruttenden, K., Mariuz, P., Rezk, N.L., Hochreiter, J., Gelbard, H., and G. Schifitto. Effects of minocycline and valproic acid coadministration on atazanavir plasma concentrations in human immunodeficiency virus-infected adults receiving atazanavir-ritonavir. Antimicrob Agents Chemother. 2008 Sep;52(9):3035-9. Epub 2008 Jun 23.
Norman, J.P., Perry, S.W., Bentley, K., Trejo, M., Reynolds, H.M., Kiebala, M., Volsky, D.J., Maggirwar, S.B., Dewhurst, S., Masliah, E. and Gelbard, H.A.. HIV-1 Tat Activates Neuronal Ryanodine Receptors with Rapid Induction of the Unfolded Protein Response and Mitochondrial Hyperpolarization. (PLoS One, in press).
Bellizzi, M.J. and Gelbard, H.A.. (in press) Infectious agents in neurodegenerative disease. In Larry R. Squire (Editor-in-Chief) Encyclopedia of Neuroscience, Academic Press, Oxford, 2008.
Perry S.W. and Gelbard, H.A.. (in press) Neuroimmunology and the Pathogenesis of HIV-1 Encephalitis in the HAART Era: Implications for Neuroprotective Treatment. In Goodkin, Shapshak, and Verma (eds.) The Spectrum of Neuro-AIDS Disorders: Pathophysiology, Diagnosis, and Treatment, ASM Press, NY.
Neurophysiology of the basal ganglia in motor control. Quantitative analysis of kinematics and muscle patterns in movement disorders such as dystonia, chorea, and cerebral palsy. Clinical research in Tourette Syndrome, cerebral palsy, and Batten Disease. (Mink)
Albin RL, Mink JW. Recent advances in Tourette syndrome research. Trends Neurosci, 2006; 29:175-182.
Perlmutter JS, Mink JW. Deep Brain Stimulation. Ann Rev Neurosci, 2006; 29: 229-257.
Tabbal SD, Mink JW, Antenor JV, Carl JL, Moerlein SM, Perlmutter JS. MPTP-Induced Acute Transient Dystonia in monkeys associated with low striatal dopamine. Neuroscience, 2006; 141: 1281-1287.
Mink JW, Walkup J, Frey KA, Como P, Cath D, DeLong MR, Erenberg G, Jankovic J, Juncos J, Leckman JF, Swerdlow N, Visser-Vandewalle V, Vitek JL. Patient Selection and Assessment Guidelines for Deep Brain Stimulation in Tourette Syndrome. Movement Disorders, 2006; 21:1831-1838.
Adams HR, Kwon J, Marshall FJ, de Blieck EA, Pearce DA, Mink JW. Neuropsychological symptoms of Juvenile-onset Batten Disease: Experiences from two studies. J Child Neurol, 2007; 22: 621-627.
Sanger TD, Bastian A, Brunstrom J, Damiano D, Delgado M, Dure, L, Gaebler-Spira D, Hoon A, Mink JW, Sherman-Levine S, Welty LJ, Child Motor Study Group. Prospective open-label clinical trial of trihexyphenidyl in children with secondary dystonia due to cerebral palsy. J Child Neurol, 2007; 22: 530-537.
Mink JW. Paroxysmal Dyskinesias. Curr Opin Pediatr, 2007; 19:652-656.
Tabbal SD, Revilla FJ, Mink JW, Schneider-Gibson P, Wernle AR, de Erausquin GA, Perlmutter JS, Rich KM, Dowling JL. Safety and efficacy of subthalamic nucleus deep brain stimulation performed with limited intra-operative mapping for treatment of Parkinson disease. Neurosurgery, 2007; 61 (Suppl 3):119-127.
Tabbal SD, Ushe M, Mink JW, Revilla FJ, Wernle AR, Hong M, Karimi M, Perlmutter JS. Unilateral subthalamic nucleus stimulation has a measurable ipsilateral effect on rigidity and bradykinesia in Parkinson disease. Exp Neurol, 2008; 211:234-42.
Karimi M, Golchin N, Tabbal SD, Hershey T, Videen TO, Wu J, Usche JW, Revilla FJ, Hartlein JM, Wernle AR, Mink JW, Perlmutter JS. Subthalamic nucleus stimulation-induced regional blood flow responses correlate with improvement of motor signs in Parkinson disease. Brain, 2008; epub ahead of print.
The Seychelles Child Development Study (SCDS) is examining the relationship between maternal nutrition, methyl mercury (MeHg) exposure from fish consumption and the motor, cognitive and general neurodevelopment of the child. The current RO1 (2005-2010) is to evaluate the 700 main cohort subjects twice at 15 and 17 years of age. The test battery will examine cognitive, motor and executive functions. The second evaluation at age 19 years is evaluating cardiac autonomic function, auditory function, and motor skills. We are also examining the inter relationship of exposure to inorganic Hg (dental amalgams) and MeHg in a separate cohort of 250 children and doing a survey of autism phenotypes in a cohort of 4,000 subjects for whom we have prenatal MeHg exposure (Myers)
Wallace JMW; Bonham MP; Strain JJ; Duffy EM; Robson PJ; Ward M; McNulty H; Davidson PW; Myers GJ; Shamlaye CF; Clarkson TW; Molloy AM; Scott JM; Ueland PM. "Homocysteine concentration, related B-vitamins and betainme in pregnant women recruited to Seychelles Child Development Study." Am J Clinic. Nutrit 87 (2008): 391-397.
Davidson PW; Sloane-Reeves J; Myers GJ; Hansen ON; Huang LS; Georger LA; Cox C; Thurston SW; Shamlaye CF; Clarkson TW. "Association between prenatal exposure to methylmercury and visuospacial ability at 10.7 years in the Seychelles Child Development Study." Neurotoxicology 29 (2008): 543-549.
Bonham MP; Duffy EM; Wallace JMW; Robson PJ; Bradbury I, Myers GJ; Davidson PW; Clarkson TW; Shamlaye CF; Strain JJ. "Habitual fish consumption does not prevent a decrease in LCPUFA status in pregnant women (the Seychelles Child Development Nutrition Study)." Prostaglandins, Leukotrienes & Essential Fatty Acids 78 (2008): 343-350.
Davidson PW; Strain JJ; Myers GJ; Wallace JMW; Robson PJ; Bonham MP; Duffy EM; Thurston SW; Georger LA; Shamlaye CF; Sloane-Reeves J; Cernichiari E; Canfield RL; Cox C; Huang LS; Janciuras J; Clarkson TW. "Nutrients from eating fish in pregnancy balance fetal methylmercury exposure". Neurotoxicology September 2008.
Strain JJ; Davidson PW; Bonham MP; Duffy EM; Stokes-Riner A; Thurston SW; Wallace JMW; Robson PJ; Shamlaye CF; Georger LA; Sloane-Reeves J; Cernichiari E; Canfield RL; Cox C; Huang LS; Janciuras J; Myers GJ; Clarkson TW. "Associations of maternal long chain polyunsaturated fatty acids, methyl mercury, and infant development in the Seychelles Child Development and Nutrition Study". Neurotoxicology September 2008.
Myers GJ; Davidson PW; Strain JJ. "Symposium on heavy metals and nutrition. Fish Consumption: Known Benefits from Nutrients, Possible Risks from Methyl Mercury." Journal of Nutrition 37 (2007): 2805-2808.
Cernichiari E; Myers GJ; Ballatori N; Zareba G; Clarkson TW. "The Biological Monitoring of prenatal exposure to Methylmercury." Neurotoxicology 28 (2007): 1015-1022.
Thurston SW; Bovet P; Myers GJ; Davidson PW; Wagner-Georger L; Shamlaye C; Clarkson TW. "Prenatal Methylmercury Exposure and Blood Pressure in the Seychelles Child Development Study of Maternal Fish Consumption." Neurotoxicology 28 (2007): 924-930.
Huang LS; Myers GJ; Davidson PW; Cox C; Fengyuan X; Thurston SW; Cernichiari E; Shamlaye CF; Sloane-Reeves J; Wagner L; Clarkson TW. "Is the Effect of Prenatal Methylmercury Exposure from Fish Consumption Non-homogeneous? Tree-structured Analysis for the Seychelles Child Development Study." Neurotoxicology 28 (2007): 1237-1244.
Development of multicenter clinical trials in pediatric neurology with a particular emphasis on 1) the treatment of neonatal seizures—a study in collaboration with the neonatalogy division and 2) treatment trials in Batten disease. Investigator in the Autism Research trials here at URMC, with an interest in understanding the efficacy of current treatments in autism and the genetic mechanisms of autism. (Kwon)
Kwon JM, Guillet R (2006) Neonatal Seizures. Journal of Neonatology 2:104-113.
Guillet R, Kwon JM (2007) Seizure Recurrence and Developmental Disabilities after Neonatal Seizures: Outcomes are Unrelated to Use of Phenobarbital Prophylaxis. J Child Neurology, 22:389-95.
Adams H, de Blieck EA, Mink JW, Marshall FJ, Kwon J, Dure L, Rothberg PG, Ramirez-Montealegre D, Pearce DA (2006) Standardized assessment of behavior and adaptive living skills in juvenile neuronal ceroid lipofuscinosis. Dev Med Child Neurol 48:259-64. View PubMed Reference
Guillet R, Kwon JM (2007) Seizure Recurrence and Developmental Disabilities after Neonatal Seizures: Outcomes are Unrelated to Use of Phenobarbital Prophylaxis. J Child Neurol. 22:389-95. View PubMed Reference
Adams HR, Kwon J, Marshall FJ, de Blieck EA, Pearce DA, Mink JW (2007) Neuropsychological symptoms of juvenile-onset batten disease: experiences from 2 studies. J Child Neurol. 22:621-7. View PubMed Reference
Guillet R, Kwon JM (2008) Prophylactic phenobarbital after resolution of neonatal seizures: survey of current practice. Pediatrics. 2008; 122:731-735 View PubMed Reference
Investigate neurobehavioral and neurocognitive phenotypes of pediatric neurologic diseases, and neuropsychological interventions, with emphases on 1) educational intervention for pediatric mild traumatic brain injury and 2) Batten Disease, including natural history studies of neurocognitive and behavioral phenotype, and studies of quality of life; 3) Collaborate or support studies of neurocognitive function in other diseases including pediatric HIV / AIDS, hypertension & kidney disease, pediatric cancer late effects. (Adams)
Waber, D.P., Silverman, L.B., Catania, L., Mautz, W., Rue, M., Gelber, R.D., Levy, D.E., Godwasser, M.A., Adams, H., Dufresne, A., Metzger, V., Romero, I., Tarbell, N.J., Dalton, V.K. and Sallan, S.E. (2004) Outcomes of a randomized trial of hyperfractionated cranial radiation therapy for treatment of high-risk acute lymphoblastic leukemia: Therapeutic efficacy and neurotoxicity. J. Clin. Oncol. 22(13):2701-2707. View PubMed Reference
Adams, H., de Blieck, E., Dure, L., Marshall, F., Mink, J.W., DeYoung, J., Levy, E., Ramirez-Montealegre, D. and Pearce, D.A. (2004) Obsessive/compulsive symptoms in Juvenile Neuronal Ceroid Lipofuscinosis (Batten Disease). Ann. Neurol. 56(suppl 8): S127.
Adams, H., de Blieck, E., Dure, L., Marshall, F.J., Mink, J. and Pearce, D.A. (2004) Neuropsychological and behavioral symptoms in Juvenile Neuronal Ceroid Lipofuscinosis (NCL-3; Batten’s Disease). Neurology 62(Suppl 5):A68-69.
Adams HR; Kwon J; Marshall FJ; de Blieck EA; Pearce DA; Mink JW. "Neuropsychological findings in Batten Disease: Experiences from two pilot studies". Journal of Child Neurology 22 (2007): 621-627. View PubMed Reference
Waber DP; Turek J; Catania L; Stevenson K; Robaey P; Romero I; Adams H; Alyman C; Jandet-Brunet C; Neuberg DS; Sallan SE; Silverman LB. "Neuropsychological Outcomes of a Randomized Trial of Triple Intrathecal Chemotherapy Versus 1800 cGy Cranial Radiation as Central Nervous System Treatment in Acute Lymphoblastic Leukemia: Findings from Dana-Farber Cancer Institute ALL Consortium Protocol 95-01". Journal of Clinical Oncology 25 (2007): 4914-4921. View PubMed Reference
Lande, MB; Adams, H; Falkner, B; Waldstein, SR; Schwartz, GJ; Szilagyi, PG; Wang, H; Palumbo, D. "Parental Assessments of Internalizing and Externalizing Behavior and Executive Function in Children with Primary Hypertension". Pediatrics, in press. View PubMed Reference
W. Mink, MD, PhD
Unit Chief, Child Neurology