Scientific Report 2003-2004 - Cleveland Clinic Lerner Research ...

The Department of Biomedical Engineering16Continued from Page 15both human studies and mathematical models.Guang H. Yue, Ph.D., is pursuing a variety ofexperimental studies (cortical control of fingermovements vis-a-vis brain electrical activity,training the nervous system to improve motorfunction in disabled patients without actualmuscle training, fatigue in patients with neurologicaldisorders, and functional magneticresonance imaging (fMRI) and movement-relatedcortical potentials in stroke patients). Among theresearch questions under study are how the braincontrols voluntary motor action and how thecentral nervous system, including the brain,adapts to various acute and chronic perturbations,such as fatigue, immobilization, training, aging,microgravity, injury or disease, with a viewtoward initiating more effective treatment ofmovement disorders, designing better rehabilitativetreatments, and reducing health care costs.This work is highly collaborative with the Clinic’sPhysical Medicine and Rehabilitation group.Cameron C. McIntyre, Ph.D., leads a newprogram involving model-based analysis of highfrequencydeep brain stimulation (DBS), inconjunction with results from PET/fMRIexperiments, to better treat parkinsonian andother movement disorders. Using the techniquesof computational neuroscience and electromagneticfield modeling, his group’s goal is toaugment experimental investigation in DBS ofthe parkinsonian nonhuman primate as well asimprove the electrode targeting and postoperativeparameter selection processes in humans. Bycoupling results from a number of sources, thegroup is creating a theoretical framework thatenhances understanding of the effects of DBSand provides a virtual testing ground for newstimulation paradigms that will yield maximumtherapeutic benefit and minimal side effects.A strong research program in OrthopaedicBiology and Bioengineering ishighlighted by integration with CCF’s OrthopaedicResearch Center. Suneel Apte, M.B.B.S.,D.Phil., investigates extracellular matrix as well asthe metalloproteases that remodel it and modifyAt left: Six images of progressive normal skeletaldevelopment in the mouse. From the laboratory of SuneelApte, M.B.B.S., D. Phil., the Section of OrthopaedicBiology and Bioengineering.Above at right: Island in the storm; trabecular bone fromthe femoral neck of an osteoporotic patient. Islands ofbone tissue with viable osteocytes (grey areas with stellateshaped cells) juxtaposed to empty spaces (black)corresponding to areas of bone removed by osteoclastsduring progression of osteoporosis. From the laboratoryof Melissa Knote Tate, Ph.D., the Section ofOrthopaedic Biology and Bioengineering.cellular behavior through extracellular proteolysis.These include enzymes of the MMP andADAMTS family. He uses transgenic mice tostudy how the body utilizes these molecules fordevelopmental processes such as skeletogenesisand lung development. This fundamental work iscomplemented by studies of the roles of thesemolecules in arthritis, inflammation and cancer.R. Tracy Ballock, M.D., focuses on translationalstudies of the growth plate in relation tochildhood obesity (especially in slipped capitalfemoral epiphysis, an obesity-related hip disease inchildren) by studying molecules called peroxisomeproliferator-activated receptors (PPARs), whichare also expressed in bone and cartilage andinterfere with thyroid hormone receptor (TR)-mediated gene transcription. This work employshuman tissue and a rat model of physeal cartilageformation and uses an instrumented surgicalstaple to measure compressive forces generated bythe physis growing against the staple. KathleenDerwin, Ph.D., probes the interface betweentendon and ligament biology and biomechanics asapplied to the design of tissue-engineeredmaterials. A key aspect of this research involvestissue engineering of tendon and ligamentsubstitutes using fibroblasts seeded onto naturalextracellular matrices.Vincent C. Hascall,Ph.D., studies thestructure, functionand metabolism ofproteoglycans,especially aggrecan,which helps tissuesresist compressiveloading in cartilage. Amajor focus is onhyaluronan, whichforms scaffolds for molecules involved in cartilageformation, oocyte fertilization, skin keratinization,colon and lung smooth muscle cells’ response toviral stimuli, and abnormal matrices synthesized inresponse to elevated glucose in vascular anddiabetic pathologies. Melissa L. Knothe Tate, Ph.D.,explores the signaling/timing of interactionsbetween bone-cell types, in regard to growth,adaptation, and repair of musculoskeletal tissuesand bone. Her group has developed innovativemethods to study mechanical load-induced fluidflow and mass transport through tissue, as well astheoretical computer models to predict flowpatterns under simulated conditions and explicatethe relationship between mechanical loadingparameters and fluid dynamics in bone. She also hasan interest in the spaces through which extravascularfluid flows to develop drug-delivery systems forskeletal tissues and for new bioactiveendoprostheses designed to optimizeosseointegration. Véronique Lefebvre, Ph.D., usesContinued on Page 17