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

Overview of Neuromuscular  and Movement Disorders

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: rbarohn@kumc.edu

Mazen Dimachkie

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 mdimachkie@kumc.edu

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

Mamatha Pasnoor

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

Raj Pawa Kelly Lyons

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: rpahwa@kumc.edu; klyons@kumc.eduwww.kumc.edu/parkinson

Jules Nazzaro

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

Richard Dubinsky

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: rdubinsk@kumc.edu

Barry Festoff

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

Philip Gallagher

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

Marco Brotto

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: brottom@umkc.edu

Paige Geiger

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

Hiroshi Nishimune

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: hnishimune@kumc.edu• http://www.kumc.edu/anatomy/nishimune.html

Mike Werle

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.

Collaborative Opportunities• Confocal and electron microscopy• Alterations in MMP levels in serum

John Stanford

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

Lab Personnel

• Hongyu Zhang, PhD• Susan Smittkamp, PhD• Yonghong Wang, MD• Jill Morris

Steve Fowler

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

Lab Personnel

• Elena Vorontsova• Shaheen Latif• Luke Mahoney

Randy Nudo

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

Paul Cheney

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

☺

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

Wen Liu

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

Carl Luchies

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

0100020003000

-4-2

02

4E

MG

0100020003000

-0.20

0.20.4

0.60.8

Time (msec)

Dec

isio

n Fu

nctio

n

0100020003000

-0.04

-0.020

0.020.04

EM

G

0100020003000

-0.0218

-0.0217

-0.0216

-0.0215

Time (msec)

Dec

isio

n Fu

nctio

n

1

2 3

45

67

8

9

10

11

12 13

14

R. MetatarsalHead 2

R. Heel

R. Tibial Wand

R. Malleolus

R. Femoralepicondyle

Rigid Body

R. Femoral WandZFpR.Foot.CGFootRZAnkleR

YFpR.Foot.CGFootRYAnkleR

XFpR.Foot.CGFootRXAnkleR

FmF

FmF

FmF

....

....

....

)81.9( −−=

−=

−=

Z

Y

X

&&

&&

&&