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 <strong>Clinic</strong>’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 Orthopaedic<strong>Research</strong> 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
The Department of Biomedical EngineeringContinued from Page 16molecular biology, cell biology, and mouse geneticengineering approaches to study the roles of Soxtranscription factors during development and inpathologies of the skeleton and hematopoieticsystem. Her group is determining how these Soxfactors control cell fate and differentiation inspecific cell lineages and how they act on targetgenes and interact with other factors to enhance orrepress transcription. Cahir A. McDevitt, Ph.D.,studies tissue and animal models to explore woundhealing in the knee joint meniscus, especially therelationships of networks of varying collagen typesand cell forms that are quiescent until wounding,whereupon mRNA levels for type I and type VIcollagen and other matrix proteins dramaticallyincrease, with the wound crevice becomingpopulated by cells that appear to come from thesuperficial zone and that can migrate into acellularareas created by apoptosis of resident cells. RonaldJ. Midura, Ph.D., pursues studies of bone remodeling,involving bone-matrix production and/ormineralization as regulated by cytokines/hormonesin normal/pathologic states. He concentrates onthe role of parathyroidhormone (PTH) in (a)maintaining Ca 2+ levels inblood by reabsorbing it fromkidney and releasing it frombone and (b) exertingsomatotrophic effects onbone formation when usedtherapeutically. His group hasfound that PTH dramaticallyaffects an osteoblast’s abilityto produce select matrixmacromolecules, alters theirassembly into an extracellular matrix, and regulatesmatrix mineralization. George F. Muschler, M.D.,is developing more effective, less invasive methodsto treat fractures/deformities, using techniques ofcell and molecular biology, growth factor expressionand action, cell matrix interaction, imageprocessing, and biomechanics. His group has (a)devised minimally invasive methods to harvest andrapidly collect bone stem cells, (b) achieved boneregeneration with fully implantable devices that usethe process of distraction osteogenesis toregenerate bone segments and lengthen limbswithout cumbersome and painful frames, (c) avoidharvesting bone from one site and transplanting itto another by exploring synthetic materials (calciumphosphate ceramics, purified collagen preparations,and some polymers) in combination with growthfactors; and (d) developed a segmental caninemodel for efficient, sensitive evaluation ofcomposite graft materials for spinal fusion.Investigators from Biomechanics (Drs. Cavanagh,Davis, van den Bogert), Neural Control (Dr. Yue)and Imaging (Dr. Powell) are also active participantsin this group.Tissue Engineering and Wound Healingis an area of research in which BME departmentmembers from Orthopaedic Biology (Drs. Derwin,McDevitt, Midura, and Muschler) and CardiovascularBiomechanics (Dr. Vesely) are also active.Edward V. Maytin, M.D., Ph.D., pursues studies inhealing of skin wounds. He studies CCAAT/Enhancer Binding Proteins via an artificial skinmodel in which keratinocytes grow on a collagenraft floating at the air-liquid interface to simulate invivo conditions that promote epidermal stratificationand differentiation-related gene expression. Hisgoals are to study epidermal homeostasis, mechanismsof ultraviolet light damage to skin, extracellularhyaluronan’s role in regulating epidermal cells,and photodynamic therapy for skin cancer and otherhyperproliferative diseases.BME’s depth and breadth of expertise aregreatly enhanced by contributions from staffmembers from other departments who have jointappointments. Among the departments (andindividuals) represented are Cardiovascular Medicine(James Thomas, M.D.), the Center for Anesthesiology<strong>Research</strong> (Paul Murray, Ph.D.),the Cole Eye Institute (DavidHuang, M.D., Ph.D.), Nephrologyand Hypertension/Dialysis (Emil P.Paganini, M.D.), OrthopaedicSurgery (Joseph Iannotti, M.D.,Ph.D., Ulf Knothe, M.D., Dr. Med.,Robert F. McLain, Ph.D), Pediatric/Congenital Heart Surgery (Brian W.Duncan, M.D.), Radiation Oncology(Urs Hafeli, Ph.D., MartinWeinhous, M.D.), Radiology(William Davros, Ph.D., Sandra S.Halliburton, Ph.D., Jean A. Tkach, Ph.D.), Thoracicand Cardiovascular Surgery (Patrick McCarthy,M.D.), Vascular Surgery (Roy Greenberg, M.D.), andPhysical Medicine and Rehabilitation (Stephen I.Reger, Ph.D.). In addition to these individuals, 14scientists from other institutions have adjunctappointments in BME.The Department of Biomedical Engineeringis committed to investigation, innovation, andthe translation of scientific discoveries intopractical applications that enhance patient care.By providing a forum in which engineers, basicscientists and physicians can interact, thedepartment plays a key role in the <strong>Lerner</strong><strong>Research</strong> Institute and in the Foundation as awhole, advancing the mission to promoteexcellence in research, education, and patientcare.Centeral image: Proliferation ofHuman CTPs and Expressionof Alkaline Phosphatase onLoaded Coralline HA disks, day9 culture. From the laboratory ofGeorge F. Muschler, M.D., theSection of Orthopaedic Biologyand Bioengineering.17
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