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Neuromuscular and Movement Disorders Division
Director: Richard BarohnCo‐director: Paul Cheney
April McVeyArthur DickBarry FestoffBarb QuaneyBrenda Hanna-PladdyCarl LuchiesGeorge VargheseHiroshi NishimuneJohn StanfordJuan Bruses
Jules NazzaroKelly LyonsMajed DasoukiMamatha PasnoorMarco BrottoMazen DimachkieMike WerlePaige GeigerPaul Cheney
Philip Gallagher Rajesh PahwaRandolph NudoRichard BarohnRichard DubinskyStephen Fowler Steven BarlowWen LiuYunxia Wang
Neuromuscular Disorders• Motor neuron disease
– ALS/PLS– Spinal Muscular Atrophy– Post‐polio Syndrome
• Peripheral Neuropathy– Acquired– Hereditary (Charcot‐Marie‐Tooth)
• Neuromuscular Junction Disorders– Myasthenia Gravis– Lambert‐Eaton Myasthenic Syndrome– Botulism
• Myopathies– Hereditary
• Muscular dystrophies• Channelopathies
– Acquired• Inflammatory –
PM/DM/IBM• Toxic – drug induced
Movement Disorders• Hypokinetic
– Parkinson’s Disease– Progressive Supranuclear
Palsy
– PD+• Multiple System Atrophy
• Corticobasal Ganglionic Degeneration
• Diffuse Lewy Body Disease– Ataxias
• Olivopontocerebellar Atrophy/Spinocerebeller
Ataxia
• Hyperkinetic– Dystonias
• Blepharospasm• Torticollis• Focal limb distonias• Dystonic spasticity
– Tremor disorders• Essential tremor• Cerebellar outflow tract• Drug induced
Neuromuscular DisordersPrincipal InvestigatorRichard J. Barohn, M.D.Chair, Department of NeurologyGertrude and Dewey Ziegler Professor
of Neurology
Training• B.A. University of Missouri – Kansas City School of Medicine• M.D. University of Missouri – Kansas City School of Medicine• Post-Doctoral training:
– Neurology Residency:• Wilford Hall USAF Medical Center, San Antonio, TX
– Neuromuscular Fellowship:• Ohio State University, Department of Neurology
• Previous Academic Positions:– University of Texas Health Science Center, San Antonio, TX– University of Texas Southwestern, Dallas, TX
Co-InvestigatorsKUMC:Mazen Dimachkie April McVeyArthur Dick Laura HerbelinMamatha Pasnoor Yunxia WangWen Liu Bill BrooksPatricia Kluding Jeffrey BurnsDoug Wright Russell SwerdlowMajed Dasouki
KU – Lawrence: Phil Gallagher
Western ALS Study GroupNortheast ALS Study GroupMuscle Study GroupALS Research GroupCINCH (Consortium for Clinical Investigation of
Neurological Channelopathies)
Areas of InterestClinical Research in Diseases of:
- Anterior horn cell (ALS)- Peripheral nerve- Neuromuscular junction (MG)- Muscle
- Muscular dystrophies- Channelopathies- Inflammatory myopathies
Active ProjectsMyasthenia Gravis1.Methotrexate
• KU PI – Barohn; MSG• R01 FD003538-01
2.Ecluzimab• KU PI – Barohn; multi-site; funded by Avinir
Muscular Dystrophy1.Gentamicin for DMD
• KU PI – Barohn; 2 U.S. sites• funded by NIH/Columbus Children’s
2.PTC124 for DMD• KU PI – Barohn; international• funded by PTC
Channelopathies1.Consortium for the Investigation of Neurologic Channelopathies (CINCH)
• Co-PI – Barohn/Co-I – Wang (Jr. Mentee); NIH/NCRR U54 RR019482
2.Therapeutic Trial of Mexiletine for NDM• PI – Barohn/5 sites/KU Coordinating Center• R01 FD003454-01
3.Dichlorphenamide vs. Acetazolamide for PP• KU PI – Barohn; funded by NIH/Rochester
ALS1.Lithium
• KU PI – McVey; WALS; funded by MDA2.Ceftriaxone
• KU PI – Barohn; NEALS; funded by NIH/MGH
3.Pramipexol• KU PI – Barohn; multisite; funded by Knopp
4.Talampanel• KU PI – Barohn; international; 5 U.S. sites• funded by TEVA
5.DNA Banking• KU PI – Barohn; ALS RG; funded by
NIH/Columbia6.Neuroimaging
• KU PI – Wang; funded by KU RI7.Dextromethorphan/Quinidine
• KU PI – McVey; multicenter; funded by Avinir
8.Rasagiline• KU PI – Wang; WALS funded by TEVA
9.VEGF• KU PI – Barohn; 4 U.S. sites; funded by
Sangamo
Collaborative Opportunities• Phil Gallagher for muscle HSP analysis• Drug Development Team – Weir/Michaelis/Standford• Wen Liu – breathing Rx in ALS• Kluding/Wright – diabetic peripheral neuropathy• Brooks/Burns – imaging in ALS• Festoff - neuropathy/myopathy/ALS• Latinis – rheumatology• Swerdlow – mitochondrial studies• Dasouki – Duchenne studies
Research Coordinators• Sheri Copeland, RN• Maureen Walsh• Mimi Michaels• Victoria Watts, RN• Laura Herbelin
Clinical Evaluators• Laura Herbelin• Alham Al-Sharman
TraineesFellows• 2 to 3 clinical neurophysiology fellows/year
•Srinivas Bandi, MD•Farhan Ahmed, MD
• 1 neuromuscular fellow/year•Faisal Raja, MD
Resident•Jeffrey Statland, MD
Medical Students• L. Whistler • S. Masrani• M. Butler • A. Phan
Email: [email protected]
Neuromuscular ResearchPrincipal InvestigatorMazen Dimachkie, MDProfessor of NeurologyDirector, Neuromuscular Section
TrainingM.D. The American University of Beirut 1988Post-Doctoral training:Neurology Residency:The University of Texas – Houston 1993EMG & Neuromuscular Fellowship:The University of Texas – Houston 1994 Previous Academic Positions:The University of Oklahoma Health Sciences Center, Oklahoma City, OKThe University of Texas Health Science Center, Houston, TX
Co-Investigators / Study GrpsRichard Barohn Arthur DickLaura Herbelin April McVey Mamatha Pasnoor Yunxia WangPatricia Kluding Russell Swerdlow Phil Gallagher Doug WrightMSG WALS NEALS CINCHAreas of InterestClinical Trials in disorders of:Anterior horn cellPeripheral nerve Neuromuscular junctionMuscle
Etiology:Neurodegenerative ImmunologicGenetic
Projects & Approaches• Muscle:
– Immunologic / Myositis:• Medi 545 in DM & PM:
KU PI – Dimachkie; multicenter; funded by Medimmune
• Etanercept in DM:KU PI – Barohn; multicenter; funded by NIH / B&W
• Rituximab in PM & DM:KU PI – Barohn; multicenter; funded by NIH / Univ. Pittsburg
• International Myositis Classification:KU PI – Dimachkie; multicenter international; funded by TMA
• SNP Analysis in Myositis:KU PI – Dimachkie; multicenter international; to be funded / Fred Miller at NIH
• Neuromuscular Research Database:• PI – Barohn; Laura Herbelin; Mimi
Michaels; 2,382 subjects enrolled
• Muscle:– Neurodegenerative / IBM:
• Arimoclomol in IBM:KU PI – Barohn; ?UK site; GCRC CReFF Grant
• Gene Microarrays Substudy of Arimoclomol in IBM:KU PI – Dimachkie; KU Neurology Ziegler Grant
– Genetic / Dystrophy:• IGF1 Myotonic Dystrophy 1:
KU PI – Dimachkie; multicenter; funded by Insmed & MDA
• Neuromuscular Junction:– Immunologic:
• Reliability Studies in MG:KU PI – Dimachkie; multicenter international; funded by MDA
Opportunities for New Collaborations
Collaborators Current & Potential:Kevin Latinis, MD PM/DMPeter Smith, PhD. IBMPhil Gallagher, PhD. IBMStan Svojanovsky, PhD. IBMRussel Swerdlow, MD IBMPaige Geiger, PhD. MuscleBarry Festoff, MD NPPatricia Kluding, Ph.D. NPRichard McCallum, MD NPDoug Wright, Ph.D. NP
Neuromuscular/ CN Fellows:Faisal Raja, MDFarhan Ahmed, MDSrinivas Bandi, MD
EMAIL [email protected]
Research Coordinators:Sheri Copeland, RN Laura Herbelin, BS – Research Instructor, CCRPVictoria Watts, RN – CCRP
Research Assistants:Mimi MichaelsMaureen Walsh
Clinical Evaluators:Alham Al-Sharmen, PTLaura Herbelin, BS – Research Instructor, CCRP
PRINCIPAL INVESTIGATOR:Mamatha Pasnoor, MDAssistant ProfessorCo-Director of Neuropathy clinicDepartment of NeurologyUniversity of Kansas Medical Center
TRAINING:Medical School: Osmania Medical College, IndiaResidency: Grand Rapids Transitional Year Program, Grand Rapids, MINeurology Residency: KUNeurophysiology Fellowship: KU
BOARD CERTIFICATION:Neurology and Neuromuscular
CO-INVESTIGATORS:Mazen Dimachkie, MDApril McVey, MDRichard Barohn, MDLaura Herbelin, BSDavid Saperstein, MD (Phoenix Neurological Center)
AREAS OF INTEREST:Diabetic Peripheral NeuropathyNeuromuscular junction disorders Muscle disorders
PROJECTS
• Cutaneous innervation in diabetic neuropathy and cryptogenic sensory neuropathy
• Vascular endothelial growth factor (SB- 509) in Diabetic Neuropathy. Sponsor: Sangamo
Gene Gene ActivationActivation
+
+
COLLABORATORS
Anatomy Department : Douglas Wright, PhD
Physical Therapy Department: Patricia Kluding,PT, PhD, Wen Lui, PhD
Gastroenterology Department: Richard McCallum, MD
•Exercise therapy for diabetic neuropathy
•Database of CIDP patients
•IVIG in Multifocal motor neuropathy. Sponsor: Baxter
•Droxidopa
•NCS sub-study in multi-focal motor neuropathy
PROJECTS
Parkinson’s Disease and Movement Disorder Center A National Parkinson Foundation Center of Excellence
Principal InvestigatorRajesh Pahwa, M.D.Laverne and Joyce Rider Professor of
NeurologyDirector, Parkinson’s Disease and
Movement Disorder Center
Training• HSC: S.I.E.S. College, Bombay, India; 1978• M.B.B.S. (M.D.): Seth G. S. Medical College,
University of Bombay, India; 1983• Resident in Medicine, K.E.M. Hospital, Parel,
Bombay, India; 1984-1985• Internship in Medicine, Baylor College of Medicine,
Houston, TX; 1987-1988• Resident in Neurology, Baylor College of Medicine,
Houston, TX; 1988-1991• Fellow in Movement Disorders, University of Kansas
School of Medicine, Kansas City, KS; 1991-1992
Previous Academic Positions• Associate Professor, KUMC Neurology, 1999 – 2004• Assistant Professor, KUMC Neurology, 1993 – 1999
Principal InvestigatorKelly E. Lyons, PhDResearch Associate Professor of
NeurologyDirector, Research and Education,
Parkinson’s Disease and Movement Disorder Center
Training• BA: University of Kansas, Psychology 1988• MA: University of Kansas, Experimental/Cognitive
Psychology 1990• PhD: University of Kansas,
Experimental/Cognitive Psychology, 1993• Post-Doctoral Fellowship: University of Kansas
Medical Center, Neurology 1993-1995
Previous Academic Positions• Instructor, KUMC Neurology, 1995 – 1998• Assistant Professor, KUMC Neurology, 1998 –
2000• Assistant Professor, University of Miami,
Neurology 2000-2003
Parkinson’s Disease and Movement Disorder Center A National Parkinson Foundation Center of Excellence
Co-InvestigatorsKUMC:Jeffrey Burns Joan McDowd Brenda Hanna-Pladdy Jules NazzaroKaren Haring Jeff SearlWen Liu Carl Luchies
KU – Lawrence:Steven Barlow Janet Hamburg Susan Kemper
National Parkinson FoundationParkinson Study GroupTremor Research Group
Areas of InterestClinical Research in Diseases of:
- Parkinson’s disease (PD)
- Parkinson plus syndromes
- Essential tremor (ET)
Clinical/Research StaffStephanie ElyMatthew FrayTamara GalesLoretta JenkinsApril LanghammerCarey Mack
DBS Programming StaffStephanie DascalosJanet Kirk
PhD StudentGurpreet Singh (PT PhD student)
Active Projects
8.Pramipexole ERKU PI – Pahwa; funded by BI
9. Exelon Patch for PD dementia
KU PI – Pahwa; funded by Novartis
10. STRIDE PD – Early use of StalevoKU PI – Pahwa; funded by Novartis
11. Fipamexole – Reduction of dyskinesiaKU PI – Pahwa; funded by Juvantia
12. Green Tea – Potential PD
neuroprotection -collaboration with Dr. Reddy, Iowa State
13. Ongoing clinical databases of all new patients 14. Ongoing clinical databases for all surgery patients
1. PROGENI – PD Genetics StudyKU PI – Pahwa; funded by NIH/NINDS
2. NET PD – Neuroprotection for PD – 5 yr study of creatine
KU PI – Pahwa; funded by NIH/NINDS
3. QE3 – CoQ10 potential neuroprotectionKU PI – Pahwa; funded by NINDS
4. POSTCEPT – longitudinal observationKU PI – Lyons; funded by NIH
5. PROBE – search for biomarkersKU PI – Lyons; funded by DOD
6. Mayo Clinic Jacksonville Udall CenterGenetic and biochemical study of brain tissue for PD and related disorders
7. Columbia University ET NIH Brain BankCollection and study of ET brain
Collaborative Opportunities• Prediction and intervention of gait and balance
disturbances in PD• Examination of muscle fatigue and weakness in
PD• Methods to improve quality of life for PD and ET
patients• Outcomes of various medical and surgical
interventions for PD and ET• Neuroprotective interventions for PD• PD dementia
Email: [email protected]; [email protected]/parkinson
Jules M. Nazzaro, M.D.Associate Professor of Neurosurgery and NeurologyAttending in NeurosurgeryKansas University Medical Center
TrainingMD: Albert Einstein College of Medicine, Bronx, NYInternship: Montefiore Hospital and Medical Center and
Bronx Municipal Hospital Center, Albert Einstein College of Medicine, Bronx, NY
Residency: New York University Medical Center, NYC, NYFellowship: Department of Neurosurgery, Memorial Sloan-
Kettering Cancer Center, NYC, NY
Areas of InterestDeep Brain Stimulation (DBS)/Neuroanatomy/NeurophysiologyBrain MRI and DBS Lead Heating – Laboratory Investigation
CollaboratorsRajesh Pahwa, MDKelly E Lyons, PhD
William Brooks, PhDRichard Dubinsky, MDTimothy Hutchin, MSJoshua Klemp, MDSang-Pil Lee, PhD
Peter Novak, MD, PhDIvan Osario, MD
Larry Ridings, MDLouis H Wetzel, MD
Projects and ApproachesDBS for Parkinson’s disease, Essential Tremor, & Primary DystoniaDBS for EpilepsyIntraoperative microelectrode recordings/neuronal signal analysis Brain MRI scanning and DBS lead (electrode) heating
Opportunities for New CollaborationsPhysics and Biomechanics-- DBS lead heating during 1.5 T & 3.0 T MRINeurophysiology -- Neuronal signal analysisNeuroradiology – Safety of MRI in DBS patientsPsychiatry/Psychology/Ethics -- DBS for depression and obsessive compulsive disorder
Hyperkinetic Movement DisordersPrincipal InvestigatorRichard Dubinsky, MD, MPHProfessor of Neurology
Training• B.A. University of Missouri – Kansas City School of Medicine• M.D. University of Missouri – Kansas City School of Medicine• Post-Doctoral training:
– Neurology Residency:• Baylor College of Medicine
– Fellowship•NINCDS/NIH Human Motor Control
– MPH KU
Co-InvestigatorsCTCC, University of Rochester (NY):Ira Shoulson, MDKarl Kieburtz, MD, MPH
MGH:Steve Hersch, MD, PhDMerit Cudkowicz, MD, MSc
Areas of InterestClinical Research in:
Huntington’s diseasePhase, 1,2,3
DystoniasDBS
Use of BoNTDystoniasSpasticity
Active ProjectsBoNT1.PREEMT, Allergan
• Phase III tx for chronic daily HA2.MERZ, INC
• Phase III studies in blepharospasm and torticollis
3.CD-PROBE, Allegan• Observation study of use of BoNT A
in patients with torticollis
Huntington’s Disease1.PHAROS
• Observational at risk study• U Roc / NINDS NHGRI• Ira Shoulson, MD PI
2.COHORT• Observational, natural history study of
people with HD and their families• CHDI• Blair Levitt, MD, PhD, PI
3.2-CARE• RCCT of CoQ10 2400 mg/day• MGH and U Roc / NIAM / NINDS• Merit Cudkowicz, MD, MSc, PI
4.CREST-E• RCCT of Creatine in HD,18 gm/d• MGH / NINDS, NIAM• Steve Hersch, MD, PhD PI
Collaborative Opportunities• Drug Development • Disease modifying genes• Biomarkers
Research Coordinators• Carolyn Gray, RN, CCRC• Janice Broyles-Gorman, RN
Email: [email protected]
Molecular mechanisms of neuromuscular, neuroinflammatory and neurodegenerative
diseasesPrincipal InvestigatorBarry W. Festoff, M.D.Professor, Neurology, Molecular & Integrative Physiology, PharmacologyDirector, Neurobiology Research Lab, KCVAMC
TrainingB.A. U Florida, GainesvilleM.D. U Miami Medical School Post-Doctoral training
Duke, Molecular NeurobiologyMiami, NeurologyNIH, NINDS, Myopathology
Sabbaticals (Paris), Neuromuscular and neurodegenerative diseases, neurothrombinology
CollaboratorsBruce Citron-USF/Bay Pines VAZhiming William Suo-KCVAMCMehmet Bilgen-MUSCShilpa Buch -KUMC Suman Kambhampati-KCVAMCRuss Swerdlow-KUMCNancy Muma-KU-LRichard Nass-IUMCAreas of InterestThrombin, thrombomodulin, transglutaminase and
mitochondria in neuroinflammation of ALS, neuro-AIDS, MGUS neuropathy and neurotrauma
Active Projects1. “Life and death” transcripts of tissue
transglutaminase (tTG) in ALS
3. Thrombin and PARs in neuroinflammation
2. “Alarmin” HMGB1 in neuroinflammation
4. Thrombomodulin (rTM) as neuroprotection
Collaborative Opportunities• EM mitochondria in ALS, models• TM domains, HMGB1 and RAGE
interaction• Nerve antigen targets in MGUS• Use of thalidomide derivates in
MGUS, ALS
Skeletal Muscle Physiology: Causes and Preventions of Atrophy
Principal InvestigatorPhilip Gallagher PhDAssistant ProfessorDirector – Applied Physiology LabHealth Sport and Exercise Science
TrainingBS: Univ. Wisc. – Green Bay, Human BiologyMS: Northern Mich. Univ., Exercise Science PhD: Ball State Univ., Human BioenergeticsPost-Doctoral Training:
Ball State University, Muscle Physiology
CollaboratorsAndrew Fry, KU-LPhill Vardiman, KU-LJoseph Donnelly, KU-LRichard Barohn, KU-MedPaige Geiger, KU-MedMichael Wacker, UMKCScott Trappe, Ball State
Areas of InterestPharmaceutical & Nutriceutical countermeasures to atrophyInflammation and inflammatory CytokinesHeat Shock ProteinsIntracellular Signaling
Active Projects• Interaction of BCAA and muscle
contractions on the Akt/mTOR pathway
• Pre-exercise heat treatment: Prevention of muscle damage
• Single muscle fiber gene expression
• Role of power on MAPK expression in skeletal muscle
• Interaction between age and activity level on skeletal muscle intracellular signaling
• Cytokine levels in active and inactive young adults
• Whey protein supplementation with resistance training
• Effects of Arimoclomol on HSP expression in sIBM patients
• Effects of phyto-nutrients on cytokine expression during intense exercise training
Damage / Ox. Stress
↑
IL-1, IL-6, IL-8, TNF- α
↑
Catabolism & Atrophy
EccentricEccentricExerciseExercise
JNKJNK
P53P53 BidBid BaxBax
Cytochrome CCytochrome C
ApafApaf--11
ProPro-- caspasecaspase--99
ApoptosomeApoptosome
PPJNKJNK
PP PP PP PP
CaspaseCaspase--33ApoptosisApoptosis
BakBak
HSP70HSP70 JNKJNK
HSP70HSP70
Collaborative Opportunities• Gene Expression• Effects of various treatments on skeletal muscle mass and function
StudentsChad Touchberry, 5th year PhDBecky Kudrna, 3rd year PhDNicole Gandy, 3rd year PhDYahya Alayafi, 1st year PhDMichael Prewitt, 3rd year MSJustin Fletcher, 2nd year MSZachary Graham, 2nd MSGregory Wallace, Undergraduate
E-C Coupling, Muscle Aging and FatiguePrincipal InvestigatorMarco Brotto, BSN, MS, Ph.D.Associate Professor of Nursing, Medicine& Biological Sciences andDirector, Muscle Biology Group (MUBIG),University of Missouri-KCAHA ReviewerCo-Director, FASEB Muscle Biology GroupJPET Editorial Board Member
Training• B.S.N. Federal University of Ceara, Brazil• M.S. (Pharmacology) Federal University of Ceara, Brazil• Ph.D. (Physiology & Biophysics), Trinity College, UK• Post-Doctoral training:
– Biophysics at Case Western Reserve University (CWRU), OH
– Cell Biology at Robert Wood Johnson Medical School (RWJMS), NJ.
• Previous Academic Positions:– Case Western Reserve University (CWRU), OH– Robert Wood Johnson Medical School (RWJMS), NJ
Co-Investigators/CollaboratorsUMKC: Leticia Brotto
Tina HinesMichael WackerJon Andresen
CWRU: Thomas Nosek and C-K Qu
RWJMS: Jianjie Ma and Noah Weisleder
University of Pittsburgh: Jerome Parness
University of Wisconsin: Hector Valdivia
Northwestern Medical School: J-P Jin
Tohoku University (Japan): Hiroshi Takeshima
Areas of InterestAnimal models of muscle researchCardiac and skeletal muscle excitation-contraction coupling mechanismsIntracellular calcium homeostasisStore-operated calcium entryAging SarcopeniaMuscle AgingMuscle DisordersMuscle Fatigue
Active Projects1. Role of Store-operated calcium entry andmitsugumin 29 in muscle fatigue. PI (Brotto), funded by AHA
2. MIP, a novel muscle phosphoinositide phosphatase with roles in muscle fatigue, aging and muscle diseases. PI (Brotto), Co-PI’s (Thomas Nosek and CK Qu, CWRU) funded by NIH
3. Genetic influence of fatigability in males vs. females, PI’s (Brotto and Hines), funded by KC Women’s Initiative
4. Animal Models of Muscle Research, PI (Brotto), funded by the School of Nursing, UMKC.
Animal Models
Treadmill and Force Plate Actimeter
Intact Muscle Contractility
Single Muscle Fiber Contractility
Skinned Muscle Fibers
Intracellular calcium measurements
Calcium Imaging
Confocal Microscopy (SOCE & Ca Sparks)
Immunohistochemistry
SDS-PAGE, Western Blotting
PCR, QRT-PCR
RNAi and other Molecular-genetic manipulations
Cell culture
Approaches
Potential Collaborative Opportunities• Phil Gallagher for functional and biochemical characterization of muscle samples from humans with
aging sarcopenia and/or different levels of fitness• Kluding/Wright – diabetic peripheral neuropathy: fatigue studies, Ca imaging studies, biochemical
and signaling mechanisms• Festoff - neuropathy/myopathy: fatigue studies, Ca imaging studies, biochemical and signaling
mechanisms• Swerdlow – mitochondrial studies in animal models of muscle research, and we can contribute with
fatigue studies, Ca imaging studies, biochemical and signaling mechanisms
Other areas of interest to collaborate:• Identification of novel & more reliable functional and biochemical biomarkers of muscle function • Identification of novel & more reliable functional and biochemical biomarkers of muscle injury/damage • Identification of early biomarkers of aging sarcopenia and muscle wasting in general• Development of new devices to stimulate muscle growth• Development of new devices to stimulate muscle recovery from injuries
Trainees2 Research Associates3 Students
Email: [email protected]
Muscle Physiology
Principal InvestigatorPaige C. Geiger, Ph.D.
TrainingUniversity of Kansas, B.A. Chemistry, EnglishMayo Graduate School, Ph.D. PhysiologyUniversity of Florence, Italy, Muscle biophysicsWashington University in St. Louis, Muscle metabolism
Areas of InterestMechanisms of insulin resistanceHeat shock protein function in skeletal muscleBrain insulin signalingEstrogen and insulin action
Co-InvestigatorsJohn Stanford, Ph.D.Russell Swerdlow, M.D.Hao Zhu, Ph.D.
Projects & Approaches• Targeting heat shock proteins to prevent insulin resistance
– Aging and high fat diet models of insulin resistance– Stress kinase inactivation, mitochondrial function
• The role of estrogen receptors in glucose regulation– OVX model in rats, NCB5OR mice– ERα/β
expression, GLUT4, NFκB• Oxidative stress/metabolic dysfunction as common pathologies
to Type 2 diabetes and Parkinson’s Disease – 6-OHDA PD model; high fat diet model of insulin resistance– CNS and peripheral metabolism, oxidative stress
Western blotPCRImmunoprecipitationEnzyme/kinase assaysImmunohistochemistryConfocal microscopy
In vitro muscle glucose uptakeIn vitro/situ muscle contraction Single fiber force & velocityExercise training: swim & treadmillIn vivo muscle plasmid transfection &
electroporation
Techniques
Synapse formation and maintenance CNS synapse and neuromuscular junction
Principal InvestigatorHiroshi Nishimune Ph.D.Assistant Professor Anatomy & Cell biology
TrainingB.S. Osaka University Japan, Molecular neurobiologyPh.D. Osaka University Japan, Molecular neurobiologyPost-Doctoral training
INSERM U. 382, Marseille FranceWashington Univ., Dept. Anatomy and NeurobiologyHarvard Univ., Dept. Molecular and Cellular biology
Co-InvestigatorsJohn StanfordPaige GeigerSteve Carlson (Washington Univ.)Y. Mori, K. Okawa (Kyoto Univ.)
Areas of InterestMolecular mechanism of synapse
formation and maintenance
Disease related to synapse integrity and Voltage gated calcium channel
Active Projects
1. Synapse organization by interaction of voltage gated calcium channel and extracellular ligand.
2. Role of N-type VGCC for organization of neuromuscular junction, knockout mice analysis.
3. Presynaptic active zone organization by the cytosolic protein-protein interaction of VGCC.
4. ALS, analysis of morphological / molecular changes of NMJs at the pre- symptomatic stage.
Collaborative Opportunities• Confocal fluorescent IHC analysis of
neuromuscular junction.• Mouse primary neuron culture.
Postdoctoral fellows• Takafumi Mizushige, PhD• Jie Chen, MD/PhD
• Email: [email protected]• http://www.kumc.edu/anatomy/nishimune.html
Neuromuscular Disorders
Principal InvestigatorMichael Werle, Ph.D.Associate ProfessorAnatomy and Cell Biology
TrainingB.S. University of Notre DamePh.D. University of Southern CaliforniaPostdoctoral. Stanford University School of Medicine
Co-InvestigatorsDoug WrightEd StevensBrenda Rongish
Areas of InterestBasic mechanisms of synapse formation,
remodeling and eliminationFocus on control of matrix
metalloproteinases at the neuromuscular junction
Active Projects1. Alterations in MMP3 levels and activity
following changes in synaptic activity.
2. Loss of activity leads to the loss of active MMP3
3. Loss of activity leads to increased production and release of pro-MMP3 (inactive form)
4. Main goal: Identify the mechanism that converts pro-MMP3 to active MMP3 at the neuromuscular junction.
Motor Function in Aging and Age- Related Neurodegenerative Disease
Principal InvestigatorJohn A. Stanford, PhD
TrainingBA – University of Mississippi (Psychology)MA – University of Kansas (Psychology)PhD – University of Kansas (Psychology)Postdoc – University of Kentucky (Neurobiology of Aging)
Co-InvestigatorsPaige GeigerHiroshi NishimuneRandy NudoTom ImigSteve Fowler (KU)Ken Ratzlaff (KU)Beth Levant
Projects• Orolingual Motor Function in Normal Aging
• Bulbar and Spinal Motor Function in Rodent Models of ALS (Geiger & Nishimune
• Isometric Force Control in Rat Model of PD
• Relationships between PD and Type II Diabetes (Geiger)
• Electrophysiological Recording of Basal Ganglia Nuclei During Behavior in Rats (Imig)
• Force Training and Orofacial Motor Cortical Plasticity (Nudo)
• PUFA’s and Parkinsonism (Levant)
• Developing Force-Sensing Gait Analyzers for Rodents (Fowler, Ratzlaff)
Mostly Behavioral, but also:
Stereotaxic ProceduresHPLC-ECMulti-Unit ElectrophysiologySome standard Molecular Biology Techniques (e.g., Western Blots, PCR)
Approaches
Response Dynamics: Measurement of the Force and Rhythm of Motor
Responses in Laboratory AnimalsPrincipal InvestigatorStephen C. Fowler, PhD
EducationBS-University of Alabama (Mathand Physics)PhD-Princeton University (Experimental Psychology)
CollaboratorsJohn Stanford, KUMCBeth Levant, KUMCMike Johnson, KU-LJackob Moskovitz, KU-LMary L. Michaelis, KU-LKen Ratzlaff, KU-LGreg Madden, KU-LGeorge Rebec, IURolf Joho, UTSWMCJeff Kleim, UFEmily Prine, UFDavid Wozniak, Wash UMark Sands, Wash U
Projects Approaches• Biophysical analysis of
antipsychotic’s behavioral effects
• Millimeter resolution mouse force tracker
• Behavioral phenotype of Fragile-X model mice
• Dynamic gait disturbances in HD transgenic model rats and mice
• Tremor in globoid cell leukodystrophy model mice
• LCPUF’s and ADHD • And others
• Behavioral– Tremor– Gait– Learning & Memory– Timing behavior– Stereotypy
• Pharmacological• Instrumentation
development• Software development• Quantitative methods
– Fourier analysis– Wavelet analysis– Specialized algorithms
Brain Plasticity and RepairPrincipal InvestigatorRandolph J. Nudo, PhD
Director, Landon Center on Aging
Professor, Molecular & Integrative Physiology
TrainingPh.D. (Psychology)
Florida State University
Post‐Doctoral Training (Physiology)
University of California at San Francisco
Collaborators/Research TeamScott Barbay
Bill Brooks
Juan Bruses
Scott Bury
Carmen Cirstea
Caleb Dunham
Pei‐chun Fang
Shawn Frost
David Guggenmos*
David McNeal
Mariko Nishibe*
Erik Plautz
Barbara Quaney
John Stanford
Ed Urban*
Theresa Jones
Jeffrey Kleim
Pedram Mohseni
Cam Teskey
*students
Areas of InterestStrokeTraumatic brain injuryMotor learningBrain prostheticsTranslational approaches
Projects & Approaches
Reorganization of Motor Cortex Following Brain
Injury
(Nudo PI)
NIH R37 NS30853
Cortical stimulation to enhance recovery after
stroke
(Nudo PI)
NIH U54 NS048126
Non‐human primate model of white matter infarct
(Frost PI)
NIH R21 NS052355
Implantable Microsystems for anatomical rewiring
of cortical circuitry: a new approach for brain
repair (Mohseni PI)
DOD QN843120
Interactive effects of NEP1‐40 and behavioral
training after focal stroke (Fang PI)
American Heart Association
Neurophysiology
Neuroanatomy
Behavioral assessment
Immunohistochemistry
Gene expression
Drug testing
Opportunities for Collaboration
Mechanisms of recovery after brain injury
• gene expression in remote areas
Development of novel interventions after brain injury
• drug delivery to promote axonal growth and guidance
• neuroprosthetics
Translational studies
• development of animal models of stroke
• development of motor and cognitive assessment scales
• validation of human neuroimaging approaches in animal models
Brain Control of Movement & Movement DisordersPrincipal InvestigatorPaul Cheney Ph.D.Professor and Chair Molecular & Integrative Physiology
TrainingB.S. SUNY, Fredonia, biology & chemistryPh.D. SUNY Upstate Medical Center, Syracuse, Physiology Post-Doctoral training
Univ. of Washington, Dept. Physiology and BiophysicsUniv. of Washington, Regional Primate Research Center
Research Assistant ProfessorUniv. of Washington, Dept. Physiology and Biophysics
CollaboratorsRaouf Behlaj-Saif, Univ. FribourgShilpa Buch Shawn FrostSang-Pil LeeCarl Luchies Randy NudoHongyu ZhangDarcy Griffin
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Behaviorally trained monkeys☺
Movement performance measures☺
Electrophysiology☺
Microstimulation of the brain☺
Single neuron recording during behavior☺
Multi-channel (20-24) EMG recording☺
Motor and sensory evoked potentials☺
Imaging
Approaches
StudentsHeather HudsonGustaf VanAckerWill Messamore
Research focusRole of cortical and brainstem descending systems in the control of movement
Active Projects1. Mapping the representation of individual
muscles in primary and secondary cortical motor areas.
2. Synaptic organization of corticospinal neurons with motoneurons – identification of muscle targets (muscle synergies).
3. Mechanism of microstimulation evoked muscle activity and movements.
4. Cortical control of lower extremity muscles.
5. Evaluation of the strength and other properties of ipsilateral corticospinal system.
6. Signal transmission through the corticospinal system.
7. Role of secondary cortical motor areas in recovery of function following primary motor cortex damage.
10%90%
Corticospinal System
Copyright 2002, Elsevier
Qigong, a mind-body approach, for ALS patients
Principal InvestigatorWen Liu, Ph.D.Associate Professor Physical Therapy & Rehabilitation Science
Co-InvestigatorsRichard Barohn, April McVey, Mazen Dimachkie, Yunxia Wang
Current Projects Improving gait and balance control in elderly and patients
with Parkinson’s disease
Acupuncture may reduce muscle spasticity in stroke survivors
Robot-aided movement training in stroke rehabilitation
Adaptive strategy in driving in patients with mild dementia
Projects in preparation Clinical outcome of qigong exercise in ALS patients
and/or patients with other movement disordersEffect of qigong exercise on neuroinflammation in ALS
patientsEffect of qigong exercise on oxidative stress in ALS
patients
Study rationalInflammation in neurodegenerative disease:
1. Glial cells respond to stress and insults by transiently up-regulating inflammatory processes.
2. These processes are kept in check by other endogenous anti-inflammatory and neuroprotective responses that return the brain to homeostasis.
3. The delicate balance in this homeostasis can be disturbed, resulting in chronic neuroinflammatory cycle that promotes neurodegenerative disease (Griffin et al., 1998 ; Craft et al., 2005).
Numerous studies have found evidence of increased oxidative stress in ALS pathogenesis. (Shaw et al., 1995; Ferrante et al., 1997; Shibata et al, 2001).
Qigong exercise in cancer patients showed a trend of improved quality of life, reduced side effects of cancer treatment, and reduced inflammation biomarker (CRP) (Oh et al., 2008).
Meditation has been reported to reduce oxidative stress (Doraiswamy & Xiong, 2007).
Qigong training significantly affected immune function in cancer patients who showed also reduced side effects of chemo and radiation therapy (Sun & Zhao, 1989; Chen & Yeung, 2002)
Collaborative Opportunities• ALS biomarkers• Neuroinflammation measurement• Oxidative stress measurement
Students• Clayton Wauneka, PhD student• Tarang Jain, PhD student• Phillip Kilmer, DPT student
Biodynamics Research Laboratory
Lab DirectorCarl Luchies Ph.D.Associate Professor, Mech. Engin.Director, BioE Graduate ProgramDirector, KU-KUT Graduate Program
TrainingB.S.L.E. Calvin College, EngineeringB.S.M.E. Univ. Michigan, Mechanical EngineeringM.S.M.E. Univ. Michigan, Mechanical EngineeringPh.D. Univ. Michigan, Mechanical Engineering
CollaboratorsPaul Cheney Randy Nudo Kelly LyonsRajesh PahwaJonathan MahnkenJanet Hamburg
Areas of InterestBiomechanics of Balance and GaitMotor Control of MovementPostural Instability in Elderly and PD.Experimentation, Instrumentation and
Modeling.
CoursesBiomechanics of Human MotionExperimental Methods in
BiomechanicsDynamic Modeling with ADAMS
Active Projects• Early biomechanical markers of postural instability
in Parkinson’s Disease.• Constraints on the recovery from a forward fall.
• Measurement and modeling of primate limb motion.
Collaborative Opportunities• Physiology• Rehabilitation• Functional imaging
Students• Molly McVey, SELF PhD student• Sommer Amundsen, SELF PhD student• Michael Haines, MS student
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