Ellen Arruda
Mechanical Engineering
Engineering

James Ashton-Miller
Mechanical Engineering
Engineering

Kate Barald
Cellular and Molecular Biology
Medical

Sybil Biermann
Surgery
Medical

Douglas W. Blayney
Hematology/Oncology
Medical

Katarina Borer
Movement Science
Kinesiology

Susan Brooks
Institute of Gerontology
Medical

Morton Brown
Biostatistics
Public Health

Steven Buchman
Surgery
Medical

Michelle Caird
Orthopaedic Surgery
Medical

Sally Camper
Human Genetics
Medical

James Carpenter
Orthopaedic Surgery
Medical

Rachel Caspari
Anthropology
LSA

Douglas Chepeha
Otolaryngology
Medical

Brian Clarkson
Cariology/Restorative Sciences
Dental

Nabanita S. Datta
Oral Medicine
Dental

Fran Farley
Surgery
Medical

John Faulkner
Institute of Gerontology
Medical

Steven Feinberg
Oral Medicine/Surgery
Dental/Medical

Eva L. Feldman
Neurology
Medicine

John Femino
Orthopaedic Surgery
Medical

Brian Fowlkes
Radiology
Medical

David A. Fox
Rheumatology
Medical

Renny Franceschi
Periodontics
Dental

William Giannobile
Periodontics
Dental

Siew-Ging Gong
Orthodontics and Pediatric Dentistry
Dental

Steven Goldstein
Surgery
Medical

Jerry Gorski
Pediatrics
Medical

Jim Goulet
Surgery
Medical

Greg Graziano
Orthopaedic Surgery
Medical

Karl Grosh
Mechanical Engineering
Engineering

Jeffrey B. Halter
Geriatrics
Gerontology

F. Claire Hankenson
ULAM
Medical

Kurt Hankenson
Orthopaedic Surgery
Medical

Robert Hensinger
Surgery
Medical

Scott Hollister
Biomedical Engineering
Engineering

Michael Ignelzi
Orthodontics
Dental

Jeff Innis
Pediatrics
Medical

Jon Jacobson
Radiology
Medical

Sunil Kapila
Orthodontics and Pediatric Dentistry
Dental

Yvonne Kapila
Perio/Prev & Geriatric
Dental

Evan T. Keller
Urology and Pathology
Medical

Michael Kilbourn
Radiology
Medical

Keith Kirkwood
Perio/Prev & Geriatric
Dental

David Kohn
Biologic and Materials Sciences
Dental

Paul Krebsbach
Oral Medicine
Dental

Robert Lash
Internal Medicine
Medical

Stan Lee
Orthopaedic Surgery
Medical

Cliff Les
Henry Ford Hospital

Chia-Ying Lin
Neurosurgery
Medical

Jane Lukacs
Nursing

Peter Ma
Biologic and Materials Sciences
Dental

Ormand A. MacDougald
Molecular and Integrative Physiology
Medicine

Laura McCabe
Physiology
Michigan State University

Laurie McCauley
Oral Medicine
Dental

Barbara McCreadie
Orthopaedic Surgery
Medical

Bruce Miller
Orthopaedic Surgery
Medical

Joshua Miller
Orthopaedic Surgery
Medical

Richard Miller
Geriatrics
Medical

Mike Morris
Chemistry
LSA

Kenneth Pienta
Urology
Medical

Bruce Richardson
Internal Medicine
Medical

Helena Ritchie
Cariology
Dental

Blake Roessler
Internal Medicine
Medical

Theodora Ross
Internal Medicine
Medical

Robert Simpson
Pharmacology
Medical

MaryFran Sowers
Epidemiology
Public Health

Russell Taichman
Periodontics
Dental

Catherine Van Poznak
Internal Medicine
Medical

Hom-Lay Wang
Periodontics
Dental

Stephen Weiss
Internal Medicine
Medical

Milford H. Wolpoff
Anthropology
LSA

Guozhi Xiao
Oral Medicine
Dental

MEMBER PROFILES

Steven Arnoczky , D.V.M.Wade O. Brinker Endowed Professor of  Veterinary Surgery; Director, Laboratory for Comparative Orthopaedic Research: Professor of Surgery (Orthopaedic), College of Human Medicine; Professor of Orthopaedic Surgery, College of Osteopathic Medicine, Michigan State University.

His research has focused on the basic science of injury, repair, and replacement of ligaments, tendons, and menisci.  These studies range from the fate of transplanted tendons used to reconstruct the cruciate ligaments of the knee joint to the development of tissue banking techniques for meniscal transplantation to the generation of tissue engineered tendons for the treatment of rotator cuff injuries of the shoulder. In addition, the lab has developed an in vivo model of retroviral transmission through the transmission of systemically infected connective tissue allografts.  This model is being used to evaluate various tissue banking procedures currently employed to inactivate viruses in allograft bone and soft tissues

Currently, the lab is investigation the role of repetitive strain in the etiology of “overuse” injuries of connective tissues. Using cell and tissue based in vitro systems the lab is examining how cell matrix interactions regulate the mechanotransduction response of connective tissues and how this may play a role in the etiology of repetitive stress injuries.

Dr. Arnoczy’s lab website is:  http://www.cvm.msu.edu/LCOR

Ellen M. Arruda, Ph.D.
Professor, Department of Mechanical Engineering, College of Engineering

Dr. Arruda’s interests are in solid mechanics with an emphasis on the testing, characterization and constitutive models of elastomers and semi-crystalline polymers.  She has developed a particular focus on studying the behavior of soft tissues to include tendon ligament and heart muscle. She studies material responses to high strain rate, impact loading and micromechanical modeling.

James A. Ashton-Miller, Ph.D.
Research Professor, Department of Mechanical Engineering and Biomedical Engineering, College of Engineering; Distinguished Senior Research Scientist, Institute of Gerontology, Medical School

Dr. Ashton-Miller’s primary research interests center around understanding the affects of aging on motor control and postural stability.  He is an expert in spine biomechanics and joint kinematics and he is particularly focused on trying to develop strategies to help in the prevention of falls in the elderly, and subsequently help to reduce fragility fractures due to the falls.  His other interests range from urinary incontinence to characterizing pain syndromes.

Kate F. Barald, Ph.D.
Professor of Cell and Developmental Biology, Associate Director PIBS, Programs in Neuroscience, Cell and Molecular Biology.

The Barald lab works on four major research problems: the role of bone morphogenetic proteins and their antagonists in the development of the vertebrate inner ear (in chick, mouse and zebrafish model systems), the development and use of inner ear stem cell and precursor cell lines for studies of molecular development and regeneration of the auditory and vestibular epithelia; the role of the neurofibromatosis 1 (NF1) gene in neuronal and glial lineage specification and survival, and the influence of hormones on NF1 gene expression and tumorigenesis in embryonic stem cell models. We also employ transgenic knock-in approaches to these problems.

Barald lab webpage:  http://www.umich.edu/~eardevel/
CDB:  http://www.med.umich.edu/cdb/ 
CMB:  http://www.med.umich.edu/cmb/faculty/barald.htm
Neuroscience:  http://www.umich.edu/~neurosci/faculty/barald.htm

J. Sybil Biermann, M.D.
Associate Professor, Orthopaedic Oncology

Dr. Biermann serves as Director of the Musculoskeletal Oncology Program at the University of Michigan.  Her clinical interests include malignant and benign tumors of soft tissue and bone, both primary and metastatic.  Her practice includes both adults and children. 
 
Dr. Biermann chairs the Multidisciplinary Sarcoma Tumor board, a collaborative cancer center group including medical and pediatric oncologists, pathologist, diagnostic radiologists, and radiation therapists.    The Sarcoma clinic meets weekly.   As one of two federally funded Connective Tissue Oncology programs, the University of Michigan Sarcoma team engages in patient care, clinical trials, and basic science research. 
 
In addition to her regional responsibilities, Dr. Biermann has been active in national committee and administrative work. She chairs the National Comprehensive Cancer Center Network Bone Tumors Panel, she is Secretary-Treasurer of the Musculoskeletal Tumor Society, Vice-Chair of the Sarcoma Committee of the Southwest Oncology Group, and Chair of the Patient Education Committee of the American Academy of Orthopaedic Surgeons.   Her active research program has included more than 76 publications in the areas of musculoskeletal tumors and in the impact of the Internet on patient education.    She serves on the OREF peer review board.
 
Department website: http://www.um-orthopaedic-surgery.org/
CV: http://www.um-orthopaedic-surgery.org/cv_biermann.htm

Douglas W. Blayney, M.D.
Medical Director for Clinic Operations

Douglas W. Blayney, who joined the University of Michigan Comprehensive Cancer Center as Medical Director for Clinic Operations and Clinical Professor of Medicine in 2003, is responsible for overseeing the operations of the Cancer Center’s clinics and for the integration of clinical research.

His current clinical and research interests include breast cancer, lymphoma and the use of electronic technology to enhance medical practice; and he has over fifty scientific publications.    Dr. Blayney practiced medical oncology and malignant hematology with Wilshire Oncology Medical Group in Pasadena California from 1986 through 2003.  Dr. Blayney has served on the Board of Directors, as well as the Committees on Clinical Practice, Cancer Education, and Online for the American Society of Clinical Oncology.  He served on the FDA’s Oncologic Drugs Advisory Committee (ODAC) from 1999-2003.

Dr. Blayney was educated at Stanford University and the University of California at San Diego (UCSD).  His internal medicine training was at UCSD, and his oncology fellowship training at the National Cancer Institute.

Katarina T. Borer, Ph.D.
Professor of Kinesiology, Division of Kinesiology, Medical School

Dr. Borer is interested in exercise endocrinology, hormonal metabolic and cardiovascular effects of training in aging.  Her research explores the mechanisms, regulatory and nonhomeostatic, which partition nutrient energy among growth and other competing behavioral and physiological processes of energy expenditure.

Susan V. Brooks-Herzog, Ph.D.
Associate Professor of Molecular and Integrative Physiology; Research Associate Professor, Institute of Gerontology, Medical School and Assistant Professor of Biomedical Engineering, College of Engineering

Dr. Brooks-Herzog’s research focuses on the mechanical properties of skeletal muscles and single skeletal muscle fibers primarily for investigations of the effects of aging and dystrophy on skeletal muscle structure and function. Contraction-induced skeletal muscle injury is initiated by mechanical disruption of the ultrastructure of small groups of sarcomeres. The mechanisms underlying differences in susceptibility to injury as well as whether injury leads directly to the progressive wasting and weakness associated with aging and dystrophy are being investigated using a combination of in vivo and in vitro experiments. Understanding the tissue, cellular, or molecular adaptations responsible for the protection from contraction-induced injury provided by conditioning are of great interest.  In addition, we are probing the effects of injury, dystrophic disease, and aging on the coupling between muscle fiber excitation and the release of activating Ca2+ into the myoplasm. These experiments involve monitoring intracellular [Ca2+] and measuring single fiber mechanics simultaneously.

Morton B. Brown, Ph.D.
Professor, Department of Biostatistics, School of Public Health

Dr. Brown is a world-renowned biostatistician.  He has been working with many of the investigators for many years in the role of providing advice in experimental design and statistical analysis.  He has also had extensive experience in designing and interpreting studies that support trials under review by the FDA.  His continuing research will be in the area of statistical consultation and analysis.

Steven R. Buchman, M.D.
Professor of Surgery, Chief of Pediatric Plastic Surgery, Director of Craniofacial Surgery, Medical School

Michelle S. Caird, M.D.
Clinical Lecturer, Pediatric Orthopaedics

Dr Caird obtained her medical degree at the University of Michigan Medical School.  She completed residency training in Orthopaedic Surgery at the University of Michigan and a Pediatric Orthopaedic Surgery fellowship at The Children’s Hospital of Philadelphia.  Research and clinical interests include osteogenesis imperfecta and fracture healing, scoliosis and spinal deformity, and pediatric trauma.

Email:  (sugiyama@umich.edu)

Sally A. Camper, Ph.D.
James V. Neel CollegiateProfessor and Chair, Department of Human Genetics; Professor, Department of Internal Medicine, Medical School

Dr. Camper is a molecular geneticist who has focused on the genetic basis of human disease.  She is also an expert in the production and utilization of transgenic and knock-out animals for basic studies.  In that capacity she serves as the Director of the Medical School Transgenic Animal Core facility.

James E. Carpenter, M.D.
Harold W. and Helen L. Gehring Associate Professor of Orthopaedic Surgery, Chair, Department of Orthopaedic Surgery, Medical School

Dr. Carpenter’s interests are in shoulder instability, knee arthroscopy and reconstruction after ligament injury.  His work involves the use of biomechanical studies in cadaveric models as well as clinical studies in operative and non-operative sports medicine treatments for joint injuries.

Rachel Caspari, Ph.D.
Lecturer III in Anthropology and Assistant Research Scientist, Anthropology Museum, College of Literature, Science and the Arts

Dr. Caspari is a paleoanthropologist with a focus on paleodemography and Upper Pleistocene human evolution. She has worked on fossil human remains from Europe, Africa and Asia to address questions surrounding the origin of modern humans. She is particularly interested in changes in population structure and life history associated with the Middle/Upper Paleolithic transition.  Her current research focuses on the evolution of longevity. Dr. Caspari is currently developing methods to more accurately estimate age at death in prehistoric remains, using MicroCT to assess age-related histological changes in dental tissues. Dr. Caspari also has a long-standing interest in the relationship between race and epistemology in paleoanthropology, and is the co-author of the award winning Race and Human Evolution (Simon and Shuster, 1997).

Douglas Chepeha, M.D., MSPH
Director of Microvascular Surgery, Department of Otolaryngology

The Microsurgical program objectives are to develop and refine reconstruction in the head and neck particularly related to large ablative defects.  The clinical volume is one of the largest in the United States and this provides significant opportunities to access translational and clinical expertice.  There is an existing ongoing clinical prospective research effort which provides an infrastructure for testing new reconstructive advances. 

In addition, there is a reconstructive clinic 3 days per month which provides an opportunity to follow and evaluate complex reconstructive issues.  This patient population is an important clinical resource for the evaluation of new reconstructive approaches.  With respect to bone research, the program is active in evaluating transport disc distraction osteogenesis, regeneration of critically sized defects in radiated and contaminated environments.  Dr. Chepeha is enthusiastic about collaboration to improve the outcome and decrease the morbidity of our patient population.

Brian H. Clarkson, B.Ch.D., LDS, M.S., Ph.D.
Chair, Department of Cariology, Restorative Sciences & Endodontics
Clifford T. Nelson Endowed Professorship

Dr. Clarkson’s research has focused on the effects of non collagenous matrix proteins of dental hard tissues on the repair and regeneration of dentin and enamel. Lately we have applied nanotechnology in the synthesis of nanorod, enamel-like crystals and prisms.

The major non collagenous protein of dentin is dentin phosphoprotein (DPP) which appears to be fundamental in initiating the nucleation mineral and controlling crystal growth during dentin mineralization. The enamel proteins especially, amelogenin, also appear to control crystal growth in enamel but by a different mechanism. Our work has focused on using atomic force microscopy (AFM) to image these crystal / protein interactions. To help us understand the mechanism of why and how proteins bind to hydroxyapatite we have used “artificial proteins” (dendrimers) which can be synthesized with end groups which give the dendrimer a positive, negative or neutral polarity. This has allowed the surface of the crystals to be probed and their charge differentials mapped. The binding of the proteins to the charged crystals surfaces has been “measured” and the effect of the strength of this protein binding on hydroxyapatite crystal growth investigated.

Using nanotechnology methodologies “borrowed” from the semi conductor manufacturing field we have recently synthesized hydroxyapatite nanorods which are morphologically, chemically and physically identical to enamel crystals. We have also been able to form enamel prism-like structures using a surfactant model. In the future we hope to be able to form laminates and / or blocks of this enamel-like material which can then be used as a synthetic fluoropatite restorative material.

Dr. Clarkson is now working with other investigators to “make a tooth”. Dr. Nor’s group is interested in pulpal angiogenesis and my laboratory along with Dr. Helena Ritchie’s are using dental pulpal stem cells and ameloblast lineage cells to regenerate the dental hard tissues.

Nabanita S Datta, Ph.D
Assistant Research Scientist, Department Periodontics/Prevention And Geriatrics

Bone is constantly remodeling. This physiological process is tightly regulated by both direct and indirect mechanisms such as osteoblast precursor cell proliferation, apoptosis, hematopoiesis, and regulation by growth factors, cytokines, and hormones. Numerous skeletal diseases are caused by the impairment of osteoblast function. Our knowledge of the genes that modulate osteoblast proliferation in the context of bone disease is still lacking. PTH and PTHrP are systemic and local regulators with major control over the process of bone remodeling. To gain a better understanding of the role of PTHrP in osteoblast growth control we have focused on several areas in defining the molecular mechanisms. These include signaling pathways to cell cycle regulation of PTHrP in osteoblasts, regulation of apoptosis by PTHrP in vivo and in vitro using knock out mice, and the role of cfos and junB in mediating PTHrP effects in osteoblasts.

Another significant research area involves the role of PTHrP in tooth eruption. The process of tooth eruption is dependent on numerous factors such as development of
functional follicle cells/PDL/cementoblasts/osteoblasts. PTHrP knock out mice have defective tooth eruption. In order to identify the transcriptional mediators and signaling molecules of PTHrP during tooth eruption we are currently trying to understand the effect of cfos and JunB gene silencing in cementoblasts and the role of PTHrP in these events.

Frances A. Farley, M.D.
Associate Professor, Department Orthopaedic Surgery, Medical School.

As a Pediatric Orthopaedic Surgeon, Dr. Farley has interests in the development of pediatric spine conditions and clinical/surgical means for preventing or treating curvature.  Her research is focused on establishing parameters that influence the development of spine anomalies and factors that contribute to the progression of spine curvature.  She has most recently developed a mouse model of congenital spine deformity, subsequent to maternal CO exposures.

John A. Faulkner, Ph.D.
Professor of Molecular and Integrative Physiology, Research Professor, Institute of Gerontology Medical School; Professor of Biomedical Engineering, College of Engineering

John Faulkner’s research focuses on the mechanical properties of whole skeletal muscles and single skeletal muscle fibers from young through old mice. He and his associates study the changes that occur in the mechanical properties of skeletal muscle fibers from muscles of wild type, knockout, and transgenic mice during and following injury, fatigue and regeneration. Skeletal muscle fibers are injured by diseases; reactive oxygen species, direct injury; extremes of temperature; ischemia; and high forces developed during contractions. The goal is to devise techniques to reduce the deficits. Age involved is a major factor in the magnitude of the injury, rate of recovery and deficits incurred.

Stephen E. Feinberg, D.D.S., Ph.D.
Professor, Department of Oral Surgery, School of Dentistry and Associate Professor, Department of Surgery, Medical School.

Eva L. Feldman M.D., Ph.D.
Associate Professor, Department of Neurology

One aspect of our research focuses on the roles of the insulin-like growth factor (IGF) family in neuroblastoma (NBL) tumorigenesis. We have reported that the IGF ligands working through the type I IGF receptor (IGF-IR) promote NBL cell growth, motility, invasion, and survival. Our laboratory has shown that IGF-I and II and the IGF-IR and IGF-IIR are expressed in NBL cell lines and in all stages of primary tumors supporting the importance of IGF expression in NBL tumorigenesis. IGF-I ligand binding via IGF-IR supports the growth and survival of NBL cell lines by modulating the expression and/or activity of various cellular components. In addition, our laboratory has shown that IGF-I exposure can protect NBL cells from apoptotic stimuli. Collectively, these data support the generally held concept that the IGF family of ligands and receptors promote NBL tumor formation, survival, metastasis, and resistance to clinical treatments, leading to a more aggressive and untreatable disease state.

During the past year, we have also become interested in the role of the IGF family in the development of osteolytic bone disease. Specifically, why do NBL tumors metastasize to the skeleton and how does the IGF system modulate this process? The RANKL/RANK system is involved in the development of prostate cancer metastases to bone. Our laboratory is currently investigating whether this pathway is involved in NBL metastases. RANKL (receptor of nuclear factor kappa β ligand), its true receptor RANK, and the decoy receptor osteoprotegerin (OPG) are important mediators of osteoclast differentiation and activity. Normally, this system is under tight control. However, tumor cells are able to secrete RANKL, which abnormally activates RANK on the surface of osteoclast cells, leading to osteolytic lesions. In addition, IGF-I (which is present in bone) may also lead to disruption of the RANK/RANKL system. Therefore, our laboratory is currently testing the hypothesis that IGF-I from bone could modulate the RANKL/OPG levels in NBL cells, promoting RANKL secretion, leading to increased osteolytic activity. These experiments may lead to the development of future therapeutic treatments aimed at preventing NBL spread to bone.

For our new endeavors in the bone field, we are developing animal models of NBL metastasis. We are currently collaborating with Drs. Evan Keller, Ken van Golen, Russ Taichman and Laurie McCauley to perform ectopic, orthotopic, and intratibial injections. These experiments will allow us to extend our in vitro observations into a vertebrate animal model.

John E. Femino, M.D.
Clinical Assistant Professor of Surgery, Department of Orthopaedic Surgery, Medical School

Dr. Femino’s interests are inankle and foot arthritis, ankle instability and lesions of the talus including avascular necrosis and osteochondral lesions.  His research focuses on hindfoot biomechanics, complex midfoot trauma, and tendon problems of the foot and ankle.  His research is both clinically based and experimental (cadaveric models).

Jeffrey Brian Fowlkes, Ph.D.
Associate Professor, Department of Radiology, Medical School and Associate Professor of Biomedical Engineering, College of Engineering

Dr. Fowlkes is a physicist and bioengineer with a research focus on medical imaging.  In particular, he has developed a number of novel approaches to measure tissue morphology and integrity, non-invasively.  Of particular note is his recent work in molecular imaging and his co-development of molecular based contrast agents for CT, ultrasound and optical imaging.

David A. Fox, M.D.
Professor, Department of Internal Medicine and Chief, Division of Rheumatology

Research in Dr. Fox's laboratory is directed at defining and characterizing pathways of human T cell activation, and the role of these pathways in the pathogenesis of autoimmune diseases. One approach used has been to generate monoclonal antibodies against T lymphocyte populations from autoimmune lesions, for example, from synovial tissue and synovial fluid derived from patients with rheumatoid arthritis. Antibodies are then screened for preferential reactivity with lesional T cells and for functional effects.

Using this approach a novel T cell surface glycoprotein, designated CD60 was identified and characterized. CD60 is highly expressed on T cells in autoimmune lesions such as inflammatory synovium or psoriatic skin. The monoclonal antibody against CD60 is mitogenic or co-mitogenic for T cells and T cell clones. CD60 is also expressed on cells with which T cells interact in ontogeny and autoimmunity, such as thymic epithelium, RA synoviocytes and psoriatic keratinocytes. Ongoing work is directed at better understanding CD60 function in T cells and synoviocytes.

Development of a new monoclonal antibody to the CD6 T cell glycoprotein has led to studies of the ability of CD6 to transmit a co-activating signal to T cells, its analysis of regulation during T cell ontogeny and activation, and its role in T cell autoreactivity. One known ligand of CD6 is CD166 (also known as ALCAM) and we have recently identified a second natural ligand for CD6, termed 3A11 which is expressed on synovial fibroblasts. Both CD6 ligands are expressed on osteoblasts.

New systems have been developed to study interactions between lymphocytes and tissue specific cells found in the joint (synovial fibroblasts). These cells are able to function as potent accessory cells for T cell activation by lectin and superantigen. Furthermore, recent data indicates that resting T cells can activate synovial fibroblasts to produce cytokines and inflammatory mediators. New monoclonal antibodies are being developed against RA synovial fibroblasts to further investigate immunologic functions of these cells. Microarray analysis of gene expression patterns is being employed to study activation responses of the synovial cells. Similar interactions with T cells have recently been found using osteoblasts.

Another focus of our research is the use of genetically modified dendritic cells as therapeutic agents to alter immune balance in vivo and treat autoimmunity. We have used dendritic cells genetically modified to express IL-4 as a novel therapy in the collagen arthritis model of rheumatoid arthritis. Such cells alter the Th-1/Th-2 balance in lymphoid organs, and a single treatment provides a long lasting therapeutic effect. Current work is analyzing the changes in gene expression in dendritic cells manipulated in this manner, in order to optimize strategies that will control Th-1 responses in vivo. Such strategies could be useful in a variety of human autoimmune diseases.

Renny Franceschi. Ph.D.
Professor, Periodontics/Prevention and Geriatrics, Associate Dean for Research, School of Dentistry

Dr. Franceschi’s laboratory is studying signals regulating the formation and functioning of osteoblasts, cells that produce and mineralize the extracellular matrix of bone, and is applying this knowledge to regenerate mineralized tissues for eventual clinical use. Research is focused on mechanisms controlling osteoblast-specific gene expression with particular emphasis on the roles of bone-associated transcription factors, hormones/growth factors, cell:extracellular matrix interactions, and mechanical force in this process. Endocrine/juxtacrine factors under study include several bone morphogenetic proteins (BMPs), fibroblast-derived growth factors and parathyroid hormone. Specific projects include:

Studies to elucidate the mechanism through which hormones/growth factors, collagen:integrin interactions and mechanical force activate two osteoblast-specific gene products, osteocalcin and bone sialoprotein. This project is specifically focused on how these factors control the activity of the bone-specific transcription factors.

Studies on the roles of bone matrix proteins, particularly bone sialoprotein and matrix Gla protein, in mineralization.

Development of virus-based gene therapy approaches to stimulate bone regeneration through the controlled expression of BMPs, FGFs and other morphogenic compounds.

The Franceschi research group is part of the University of Michigan Musculoskeletal Research Center and the Center for Craniofacial Regeneration, an interactive group of researchers in the Schools of Medicine, Dentistry and Engineering having the common goal of conducting basic and applied research directed toward   treating diseases of mineralized tissues.

His lab website is at: http://www.biochem.med.umich.edu/biochem/research/profiles/franceschi.html

William V. Giannobile, D.D.S., D.M.Sc.
William K. and Mary Anne Najjar Professor, Department of Periodontics/Prevention and Geriatrics, School of Dentistry, Associate Professor of Biomedical Engineering, College of Engineering

Dr. Giannobile’s research interests are in the area of polypeptide growth factors and their relationship to bone regeneration and homeostasis. He has developed several unique therapeutic approaches to treat periodontal bone loss secondary to a variety of local and systemic disorders.  He also has an interest in the effects of age on bone homeostasis.

Steven A. Goldstein, Ph.D.
Henry Ruppenthal Family Professor of Orthopaedic Surgery and Bioengineering; Professor in Mechanical Engineering, and Senior Research Scientist in the Institute of Gerontology.

His research is focused on studying mechanical and biologic stimuli of bone formation, regeneration and adaptation. Using a hierarchical approach, the laboratory tests hypotheses across multiple scales, ranging from signaling pathways associated with mechanotransduction to biomechanical material property characterizations. These studies have lead to the development of numerous devices to treat orthopaedic conditions including surgical instruments and artificial joint components.

Another significant research area involves the use of transgenic, knock-out and knock-in murine models to study structure function properties of bone. Using a series of unique assays to characterize the skeletal phenotype of these animals, the work has led to some unique insights into a variety of human diseases, as well as the influence of age on bone properties.

Along with several colleagues, he has developed a method of delivering genes to wound sites, promoting “in situ tissue engineering”, to treat bone defects, skin ulcers and ischemic heart disease. In addition to investigating the potential of localized gene therapy for wound repair, Dr. Goldstein is also studying cell/matrix interactions and how physical forces can augment these relationships.

More Information:
Orthopaedic Research Laboraories: http://www.orl.med.umich.edu/orl/orl.html
Personal Web page: http://www.orl.med.umich.edu/orl/orl/html/people/sag

Siew-Ging Gong, Ph.D.
Assistant Professor, Department of Orthodontics and Pediatric Dentistry, School of Dentistry.

Dr. Gong’s research interests are in the molecular regulation of craniofacial growth and craniosynostosis.  Her current program is focused on the mechanism of action of the Msx-2 gene and its mutation that has been associated with craniosynostosis.  She is particularly interested in the genes that may be involved in perturbations of craniofacial development.

Jerome L. Gorski, M.D.
Professor of Pediatrics and Communicable Diseases and Associate Professor of Human Genetics, Medical School

Dr. Gorski’s research program is designed to elucidate the molecular genetics of inherited developmental anomalies, particularly those that result in structural birth defects.  His primary focus is studying developmental disorders of skeletal formation.  His current work focuses on molecular genetics of faciogenital dysplasia and the gene responsible for this disorder FGD1 and its influence on the cascade of genes that are expressed which are part of the pathway that regulates cell growth and differentiation.  His long-term goals are to understand signal transduction pathways and mammalian morphogenesis and gain a more thorough understanding of skeletogenesis.

James A. Goulet, M.D.
Professor and Director of Orthopaedic Trauma Service, Department of Orthopaedic Surgery, Medical School.

Dr. Goulet is an Orthopaedic Surgeon and the Director of the Orthopaedic Trauma Service at the University of Michigan Medical Center.  His research interests are in studying the affects of mechanical and biological stimulation on bone repair, and in particular, their application in reconstruction after significant skeletal trauma.  Currently, he is studying the role of cell-based therapies for enhancing fracture repair.  He is also involved in clinical studies utilizing recombinant proteins as a way to stimulate bone formation in defects.

Gregory P. Graziano, M.D.
Associate Professor of Orthopaedic Surgery, Department of Orthopaedic Surgery, Medical School

Dr. Graziano’s major interests are in spinal deformities, spinal fractures including cervical, thoracic and lumbar, stenosis, ankylosing spondylitis, spinal surgery-primary and salvage.  His research is focused on ankylosing spondylitis, spinal biomechanics, spinal fixation, and rheumatological disease of the spine.  His work includes the use of animal models to study bone regeneration and cadaveric studies of fixation biomechanics.

Karl Grosh, Ph.D.
Associate Professor of Mechanical Engineering and Associate Professor of Biomedical Engineering, College of Engineering

Dr. Grosh’s interest is in the analysis of cochlear mechanics and the development of constitutive models for force generating mechanisms.  He has long-term interests in the area of mechanotransduction and anisotropic material characterization.

Jeffrey B. Halter, M.D.
Professor of Internal Medicine and Chief, Division of Geriatric Medicine; Director, Geriatrics Center; and Research Professor and Director, Institute of Gerontology

The research carried out in Dr. Halter's laboratory encompasses two primary areas: neuroendocrine regulation of metabolism in aging and in type 2 diabetes mellitus, and regulation of autonomic nervous system function. Dr. Halter's laboratory studies potential mechanisms that contribute to hyperglycemia observed in some elderly people and in patients with type 2 diabetes mellitus. These studies involve defining quantitative aspects of pancreatic beta cell function and insulin action in young controls and elderly patients with normal glucose metabolism, impaired carbohydrate tolerance, or overt type 2 diabetes. Related studies are investigating pancreatic islet adaptation to insulin resistance in human aging and hypertension by studying pancreatic beta cell function in relationship to measurement of insulin resistance.

Human aging is associated with a number of alterations of autonomic nervous system function including changes in rates of norepinephrine release and metabolism as well as alterations in catecholamine responsiveness of tissues. Ongoing studies have used tracer infusions of catecholamines to study the kinetics of their release and removal. Pharmacologic tools are being used to study regulation of norepinephrine release and removal in human aging and age-related diseases such as hypertension and depression. Adrenergic responsiveness is being studied by measurements of adrenergic receptor function and coupling to the adenylate cyclase system and by in vivo vasoconstriction responses to catecholamines.

Additional information:
Geriatrics Center: http://www.med.umich.edu/geriatrics/
Institute of Gerontology: http://www.iog.umich.edu/

F. Claire Hankenson, D.V.M.
Clinical Assistant Professor of Laboratory Animal Medicine, Medical School

Dr. Claire Hankenson is a laboratory animal veterinarian and a faculty member in the Unit for Laboratory Animal Medicine.  Her interests are in the development of animal models of human diseases.  In addition to her clinical practice, she is particularly interested in characterizing growth dynamics of the spine in murine models and the influence of specific genetic markers on morphology.

Kurt D. Hankenson, D.V.M., Ph.D.
Assistant Professor of Orthopaedic Surgery, Cell and Developmental Biology and Laboratory Animal Medicine, Medical School

The long-term goal of Dr. Hankenson’s research program is to better understand molecular control mechanisms in bone so that we can develop treatment regimens to expedite fracture healing and prevent or treat osteoporosis. Specifically he is focused on studying the role of non-collagenous extracellular matrix (ECM) proteins as modulators of osteoblast biology.  Currently the research is focused on studying the influence of the ECM on MSC proliferation, fate determination, and differentiation, and examining how the ECM acts, not as a scaffold, but dynamically to modulate skeletal regeneration.  They utilize traditional cellular and molecular biology tools in vitro for much of the work, along with genetically engineered murine models.

Robert N. Hensinger, M.D.
Professor of Orthopaedic Surgery, Department of Orthopaedic Surgery, Medical School

Dr. Hensinger is a Pediatric Orthopaedic Surgeon.  His interests are in spinal deformity in children, as well as in the etiology and progression of developmental anomalies in an orthopaedic population.  One of his current research interests is evaluating the affects of carbon monoxide on the incidence of spinal deformity.

Scott J. Hollister, Ph.D.
Associate Professor, Department of Biomedical Engineering, Department of Mechanical Engineering, College of Engineering.

Dr. Hollister’s research programs relate to investigating mechanical influences on bone adaptation.  More importantly, he directs a very large research program in the area of tissue engineering and structural optimization of bone replacement scaffolds.  He is an expert in finite element methods and has established novel algorithms enabling microstructural computational models to be developed.  He has also begun to apply his structural optimization paradigm to the development of tissue-engineered constructs for other tissues including ligament, disc and nerve.

Michael A. Ignelzi, Jr., D.D.S., Ph.D.
Associate Professor of Dentistry, Department of Pediatric Dentistry, School of Dentistry

Dr. Ignelzi is interested in evaluating the molecular and genetic basis of craniofacial development.  He is specifically exploring genetic and biomechanical mechanisms that regulate normal and abnormal suture morphogenesis.  In these studies, he uses a genetic mouse model of craniosynostosis in a combined in vivo and in vitro study to identify the signaling mechanisms responsible for this craniosynostosis.  Dr. Ignelzi is also interested in the application of distraction osteogenesis in the craniofacial skeleton and the affects of localized mechanical loads on tissue differentiation during distraction.
 
Jeffrey W. Innis, M.D., Ph.D.
Associate Professor, Human Genetics and Associate Professor of Pediatrics and Communicable Disease, Medical School

The major focus of Dr. Innis’ laboratory has been in identifying and understanding the pathogenetic basis of HOX gene mutations, particularly Hoxa13.  He is interested in understanding the normal function of this transcription factor in embryonic patterning of the limb skeleton, genitourinary system and placenta.  His laboratory has also demonstrated that dramatic differences exist between and among the forelimbs and hindlimbs of animals.  The transcription factors Pitx1, Tbx5, and Tbx4 exhibit exclusive expression in the developing lower limbs; whereas Tbx5 is expressed in the upper limb.  He has hypothesized that additional, critical genes exist within these pathways that participate in the regulation of Pitx1, Tbx5, or Tbx4 expression and/or are downstream targets of these transcription factors.  He has used serial analysis of gene expression to identify candidate genes for forelimb- or hindlimb-specific skeletal and muscle patterning.

Jon A. Jacobson, M.D.
Associate Professor of Radiology, Medical School

Dr. Jacobson is a relatively new faculty member at the University of Michigan and a bone Radiologist.  His area of expertise is in musculoskeletal imaging and is particularly interested in bone densitometry and bone imaging.  His research goals are to evaluate the power of radiologic imaging techniques in making estimates of bone integrity.  He is also interested in the use of these technologies in assessing the stages of fracture healing.

Qiming Jin, D.D.S., Ph.D.
Health Science Research Associate I, Periodontics/Prevention and Geriatrics, School of Dentistry

Periodontitis is one of the most common inflammatory diseases in adults, which results in alveolar bone absorption, periodontal ligament break, and cementum destroy. Dr. Jin is working on periodontal tissue regeneration, especially on the reconstruction of periodontal tissues with growth factor gene therapy (e.g. PDGF and BMP) and cell therapy.

Sunil D. Kapila, Ph.D.
Robert W. Browne Professor of Dentistry in Orthodontics, Department of Orthodontics and Pediatric Dentistry, School of Dentistry

The overall theme of Dr. Sunil Kapila’s studies is to understand the hormonal basis for temporomandibular joint disorders (TMJDs), bioengineering mature heterogenous fibrocartilaginous tissues and determining the mechanisms for fibronectin fragment-induced for osteolysis in periodontal disease.

Yvonne L. Kapila, D.D.S., Ph.D.
Associate Professor of Dentistry, Department of Periodontics/Prevention and Geriatrics, School of Dentistry

Research in Dr. Yvonne Kapila’s laboratory is focused on understanding the mechanisms by which the extracellular matrix (ECM) regulates cell survival and osteolysis in periodontal tissues. Dr. Kapila’s studies also extend into understanding how the ECM regulates survival signals as part of oral oncogenesis.

Madhav Karunakar, M.D.
Assistant Professor of Orthopaedic Surgery, Department of Orthopaedic Surgery, Medical School

Dr. Karunakar is an orthopaedic traumatologist with a research interest in physical and biologic influences on fracture repair.  He has just recently joined the faculty and has begun to establish animal model studies to investigate critical factors influencing the patterns of bone or cartilage differentiation.

Evan T. Keller, D.V.M., Ph.D.
Assistant Professor, Laboratory Animal Medicine Unit, Assistant Professor, Pathology and  Research Professor, Institute of Gerontology

Dr. Keller obtained a Doctor of Veterinary Medical degree from University of California, Davis in 1985.  After several years of private practice, he performed a Residency in Medical Oncology at the University of Wisconsin, Madison and obtained Board Certification in 1990.  In 1996, he obtained a Ph.D. in Developmental Biology from the University of Wisconsin, Madison.  He then served as an Assistant Professor of Medicine from 1996-1998 in the Glennan Center for Geriatrics and Gerontology at Eastern Virginia Medical School, Norfolk, Virginia.  In 1998, he became an Assistant Professor of Comparative Medicine and Pathology at the University of Michigan, Ann Arbor.  He was promoted to Associate Professor in 2001.  In 2005, Dr. Keller joined the Department of Urology and was promoted to Professor.  Dr. Keller has served as Deputy Editor for the Journal of Gerontology: Medical Sciences.  He is currently Director of the Nathan Shock Center Mutant and Transgenic Rodent Core, Co-Director of the Cancer Biology Program of the Comprehensive Cancer Center.  He is on the Scientific Advisory Committee for the American Federation for Aging Research.

His lab’s web page is at:  www.umich.edu/~etklab

Noboru Kikuchi, Ph.D.
Roger L. McCarthy Professor of Mechanical Engineering, College of Engineering

Dr. Kikuchi is a Professor in the Department of Mechanical Engineering in the College of Engineering.  He is an international expert in topologic optimization and in computational modeling of materials and structures.  His research focus is in structural optimization and the development of algorithms to assist in the design of optimal structures.

Michael R. Kilbourn, Ph.D.
Professor of Radiology, Medical School

Dr. Kilbourn’s research interests are in the development and application of the radionuclide imaging methods PET (positron emission tomography) and SPECT (single photon emission computed tomography) to the study of biochemical processes in the living human and animal subjects.  Current projects include development and application of radiolabeling methods for in vivo studies of stem cell movement and deposition in skeletal defects, and development of radioligands for neurochemical processes including enzymes, transporters and receptors.  Research projects include design and development of new radiolabeled compounds, evaluation in rodents and monkeys using autoradiography and in vivo PET and SPECT imaging, and eventual implementation of new radiopharmaceuticals in clinical research.

Keith L. Kirkwood, D.D.S., Ph.D.
Assistant Professor, Periodontics/Prevention/Geriatrics

His laboratory has a broad interest in inflammatory cytokine gene expression and signal transduction mechanisms during inflammatory bone diseases, including periodontal diseases, and oral cancer. Using cell and molecular biology techniques to address questions relative to mechanisms of gene expression>

Current lab focus areas include interleukin (IL)-6 regulation and receptor activator of NFκB ligand (RANKL) through p38 mitogen activated protein (MAP) kinase pathways. Specifically, we are interested in understanding post-transcriptional regulation of IL-6 expression in osteoblastic cells and p38 MAPK regulation of RANKL expression in bone marrow stromal cells and periodontal ligament fibroblasts. We have generated several reporter gene constructs in MC3T3-E1 cells containing R-luciferase-IL-6 3’UTR in a tet-off background. Additional GFP-based reporters systems for IL-6 3’UTR elements have been generated in SV-40 Large T antigen immortalized MC3T3-E1 cells called MCT. Using MAPK signaling intermediates in mammalian expression constructs IL-6 mRNA stability elements and cell signaling intermediates will be defined in osteoblasts.

Other studies, which have been initiated, recently involve understanding the role of IL-6 in squamous cell carcinoma invasion into bone and collagenase-3 regulation in periodontal tissues. Our laboratory has ongoing collaborations with other laboratories in cytokine regulation and tissue engineering. One area of active collaboration uses engineered skin equivalents to secrete functional insulin in a controlled manner. Thus, our laboratory has diverse areas of application relative to oral health with underlying goals of understanding complex mechanisms governing cell signaling and gene expression.

David H. Kohn, Ph.D.
Professor, Departments of Biologic and Materials Sciences, School of Dentistry and Biomedical Engineering, College of Engineering

Our research program focuses on two aspects of biomineralization.  First, we seek to understand how the organizational hierarchy of mineralized tissues results in mechanical competence (or, conversely, increased susceptibility to damage/fracture).  Second, we seek to mimic aspects of Nature's biomineralization strategies as a design basis for developing systems that may be used to address hypotheses regarding cell and molecular function.  Regarding the first aspect of our program, we seek to establish structure-function relations in mineralized tissues and study functional adaptation of these tissues in response to perturbations in the local microenvironment (e.g. alterations in mechanical loading, interactions with biomaterials, disease, aging).  There are two guiding principles to our analysis of structure-function relations: it is highly integrated - we develop correlations between mechanical properties, crystal structure/orientation, protein orientation, chemical composition and gene expression; and we seek to establish these correlations at different levels of organizational hierarchy - from the whole bone-level down through the tissue and ultrastructural-levels to the protein and gene-levels.  Regarding the second aspect of our program, biomimetic strategies are used to develop model systems in which biological output (in-vitro and in-vivo) can be quantitatively related to a well-controlled engineering input.  A more long-term, applied and clinically-motivated goal is to ultimately utilize this information to develop approaches to replace and/or regenerate tissues.  In an effort to create biomaterials that modulate biological response in a controlled manner, we synthesize, characterize and evaluate more biologically-based biomaterials.  Our biomimetic approach involves exploiting aspects of 3 strategies used by Nature: organic template-mediated self assembly and mineralization, functional gradients, and environmental responsiveness. 

Lab Website: http://www-personal.umich.edu/~dhkohn/

Paul Krebsbach, D.D.S., Ph.D.
Donald A. Kerr Professor of Oral Pathology, Department of Oral Medicine/Pathology/Oncology, School of Dentistry; Associate Professor of Biomedical Engineering, College of Engineering

Dr. Krebsbach’s laboratory is investigating methods for studying bone remodeling and increasing bone formation in vivo.  He has developed in vivo culture methods to expand bone marrow stromal cells derived from mouse and human bone marrow aspirates and has shown that these cells are capable of forming new bone in an animal model.  He is interested in exploring the affects of aging on the osteogenic potential of marrow stromal fibroblasts and also looking at the affects of cell signaling molecules known to affect bone formation on the osteogenic capacity of the stromal fibroblasts.

Robert W. Lash, M.D.
Clinical Associate Professor of Internal Medicine, Medical School

Dr. Lash’s research efforts relate to issues concerning osteoporosis and metabolic bone diseases.  In particular, he has three research programs under development.  He is interested in characterizing the effects of organ transplantation and its associated therapies on bone health and the development of osteoporosis.  Secondly, he is evaluating new therapies for the prevention of osteoporosis in perimenopausal women, and finally, his program is aimed at the development and evaluation of educational programs for physicians in training in the prevention and treatment of metabolic bone disease.

Stanley S. Lee, M.D.
Clinical Lecturer in Orthopaedic Surgery, Department of Orthopaedic Surgery, Medical School

Dr. Lee’s clinical interests are in degenerative conditions of the cervical and lumbar spine, scoliosis and deformity, minimally invasive spine surgery, fractures and tumors of the spine.  His research interests are in investigating motion preservation techniques in the cervical and lumbar spine, spine biomechanics, long-term outcomes in scoliosis and spinal deformity correction.

Clifford M. Les, D.V.M., Ph.D.
Senior Staff Scientist, Henry Ford Hospital; Associate Professor, Department of Anatomy/Cell Biology, Wayne State University School of Medicine

Dr. Les’ major research interests involve the mechanisms of alterations in bone material and structural viscoelastic properties that accompany estrogen depletion, as well as the early compact bone remodeling, mineralization, tissue-aging, and cellular distribution patterns in estrogen depletion that eventually lead to alterations in compact bone tissue material property distribution (e.g., density, modulus, post-yield strain).  In addition, his laboratory is investigating the mechanisms of compact bone growth factor deposition and their relationship with physical loading.

Chia-Ying Lin, Ph.D.
Research Investigator, Department of Neurosurgery, School of Medicine and Biomedical Engineering, College of Engineering

Dr. Lin’s research interests involve incorporating interdisciplinary efforts from clinical/surgical, engineering, and biology disciplines focused on spine biomechanics, reconstruction, regeneration, and clinical outcome research.

Jane Lukacs, Ph.D.
Assistant Research Scientist and Research Fellow, School of Nursing

Dr. Lukacs conducts clinical research studies in mid-life women at the transition to menopause.  Broadly, her lab examines how age, menopause and vitamin nutriture are associated with bone biomarkers and bone density.  One specific focus is on the differential influence of hormone status (estradiol) and vitamin nutriture (plasma phylloquinone, serum 25 hydroxy vitamin D, serum retinol) on one bone biomarker (percent uncercarboxylated osteocalcin [%ucOC] that has been associated with the risk of hip fracture in elderly women.  Their long term objective is to test supplement interventions utilizing vitamins K and D together with calcium for the ability to enhance carboxylation of osteocalcin and whether this enhances bone mineral density or bone architecture at mid-life in premenopausal or postmenopausal women.

Peter X. Ma, Ph.D.
Associate Professor of Biologic and Materials Sciences, Biomedical Engineering, and Macromolecular Science & Engineering

Research Activities
Polymeric Biomaterials: Development and structure-property relationship studies of polymer systems of biomedical importance, such as biodegradable polymers, bioactive polymer materials, and mechanically superior polymeric multiphase materials.

Tissue Engineering: Understanding polymer-cell interactions, and the signal and substrate requirements for cell proliferation and tissue regeneration in three dimensions to create functional tissues.

Biomimetic Materials: Development of novel synthetic materials inspired by natural materials.

Nano-featured Biomaterials: Nano-fibrous matrix and nano spheres for tissue engineering and controlled release of regulating factors; biomimetic polymer/ceramic nano composite materials for mineralized tissue engineering.

Phase-separation and Self-assembly: Physical mechanisms and biomedical applications of three-dimensional ordered structure formation, especially at the nanometer scale.

Biomechanics: Biomechanical behavior of engineered tissues in relation to biochemical composition, morphology and function.
Functional polymers: ion-containing polymers and electro-active polymers.

Ormond A. MacDougald, Ph.D.
Associate Professor, Department of Molecular and Integrative Physiology, University of Michigan School of Medicine

One of the goals of my research program is to determine the molecular mechanisms by which extracellular signals regulate mesenchymal cell fate decisions. Mesenchymal stem cells have the capacity to differentiate into a number of cell types, including adipocytes, osteoblasts and myocytes. While the focus of my lab has been on defining the genetic program of adipogenesis and its regulation by Wnt signaling, we are now extending this line of research to signals that determine whether stem cells differentiate into adipocytes or osteoblasts. Understanding the switch between these two cell types is relevant to human physiology because in a variety of clinical conditions, decreases in bone mass are typically accompanied by increases in marrow adipocytes. We have pioneered investigations into the role of Wnt10b as an inhibitor of adipogenesis in cultured preadipocytes and in transgenic mice. In addition to having less adipose tissue, mice that express Wnt10b in adipocytes and bone marrow have a four-fold increase in trabecular bone. This appears to be a direct effect of Wnt10b on fate of meschymal precursors because activation of Wnt signaling in pluripotent cell lines increases osteoblastogenesis and decreases adipogenesis. Evidence that it is Wnt10b that specifically plays a role in fate of MSCs comes from our observation that Wnt10b -/- mice have ~30% less trabecular bone. Although not as fully developed, there is considerable in vitro evidence that Wnt signaling also controls cell fate decisions between adipocytes and myocytes. As Wnt10b expression declines in mice as they age, this signaling molecule may be integral to the increase in adiposity and decrease in bone and muscle that occurs after midlife. Understanding the role of Wnt signaling in the development of adipose tissues, bone, and muscle will provide important insight into the medical problems of obesity, type II diabetes, and osteoporosis, all major health risks in the United States.

http://www-personal.umich.edu/~macdouga/MacDougaldLab.html

Jill A. Macoska, Ph.D.
Associate Professor of Surgery, Department of Urology, Medical School.

Dr. Macoska’s research interests are in the cellular and molecular events involved in early malignant transformation.  Elucidation of signaling pathways disrupted in tumor cells deleted for the short arm of chromosome 8 (8p). Her laboratory has shown that haploinsufficiency for the short arm of chromosome  8 and transcriptional downregulation for genes mapping to 8p are largely  coincident in tumor cells.  Through this work, they identified several candidate tumor suppressor genes mapping to 8p. Antibodies for the protein products  of many of these genes are available, and they are now able to examine  the functions of these proteins in specific signaling pathways in these  cells.  The laboratory has also identified a novel scaffolding protein, PDZK3 (aka AIPC, PDZD2, KIAA0300), characterized  by six PDZ protein-protein binding domains. PDZK3 is over-expressed at the transcript and protein levels in epithelial cells from prostate tumors and preneoplastic lesions, but not benign prostate glands.  Further work with this protein will elucidate whether PDZ2 or PDZ3 binds delta catenin preferentially or whether this is a syntenic interaction;  whether enhanced cellular motility and invasive ability depend on PDZK3/delta  catenin binding, and whether several splice variants of PDZK3 that  truncate or disrupt the PDZ2-PDZ3 region demonstrate differential delta-catenin  binding and phenotypic expression.

Laura R. McCabe, Ph.D.
Associate Professor, Department of Physiology and Department of Radiology, Michigan State University

Dr. McCabe’s laboratory is examining the cellular and molecular mechanisms causing decreased osteoblast function (synthesis of bone) under conditions of stress or lack of stress. The importance of a force “stress” on osteoblast differentiation is being examined by culturing osteoblasts under simulated microgravity conditions as well as hyper-gravity conditions. We have found that both situations alter osteoblast signaling pathway activation (p38 and ERK), transcription factor activities (AP-1 and SRE) and ultimately gene expression.  We have previously shown that modulation of specific AP-1 family members can have a dramatic effect on osteoblast gene expression and phenotype, thus significant changes in AP-1 member expression resulting from changes in gravitational force could activate or suppress bone formation.  Another stress to osteoblasts occurs when they are grown under hyper-osmotic conditions as seen in diabetes.  Exposure to elevated glucose or other osmotic factors causes an increase in p38 activation, c-Jun expression, CRE and AP-1 transactivation, and significantly changes osteoblast gene expression and phenotype in vitro and in vivo.  We are focusing on understanding how conditions of stress cause changes in signaling, perhaps by changes in cell shape or cytoskeletal architecture, and how these changes result in long-term modifications in transcription factor activities, gene expression and bone formation. 

Laurie K. McCauley, D.D.S., Ph.D.
William K. and Marry Anne Nijjar Professor of Periodontics, Professor of Dentistry, Department of Periodontics, School of Dentistry; Professor of Pathology, Medical School

Dr. McCauley’s research centers on the role of parathyroid hormone in bone metabolism.  Her long-term focus is to determine the mechanisms of PTH action in bone as well as the role of PTHrp.  In recent collaborations established with Drs. Goldstein, Ma, and Krebsbach, she has been developing tissue engineering strategies to stimulate bone formation.  Finally, she has a significant interest in mechanisms of skeletal metastases and is one of the co-investigators and project leaders in the funded program project on skeletal metastases in prostate cancer.

Barbara R. McCreadie, Ph.D.
Research Assistant Professor, Department of Orthopaedic Surgery
Research Investigator, Department of Biomedical Engineering

Dr. McCreadie’s research is focused on bone structure and function. Specific interests include describing structural changes with age leading to osteoporosis, and elucidating the cellular mechanisms that result in these structural changes. Additional interests include changes in bone during pregnancy.

Dr. McCreadie employs both computational and experimental approaches to scientific questions. Finite element modeling, image processing, and image-based characterization of geometry are the primary computational methods currently employed. Experimental approaches include multiple methods to quantify bone mechanical properties, Raman spectroscopy (in conjunction with M. Morris) to evaluate bone chemical composition, and quantification of bone structure and cellular function from microCT and histological slides.

Dr. McCreadie’s web page: http://www.orl.med.umich.edu/mccreadie/index.html
BME: http://www.bme.umich.edu
Orthopaedic surgery: http://www.um-orthopaedic-surgery.org/

Bruce S. Miller, M.D.
Clinical Lecturer in Orthopaedic Surgery, Department of Orthopaedic Surgery, Medical School

Dr. Bruce Miller’s clinical interests are in Sports Medicine with a focus on arthroscopy and arthritis/cartilage surgery of the shoulder, elbow, and knee.   His research has two components.  The first is an interest in the biomechanics of reconstruction procedures such as opening wedge high tibial osteotomy.  The second and more significant interest is in the development of cell-based therapies for cartilage repair.  This has lead to a program utilizing local or systemic delivery of stem cells to promote repair.  His current emphasis is on the development of murine models and imaging technology to monitor the migration of the cells.

Joshua D. Miller, M.D., Ph.D.
Assistant Professor of Orthopaedic Surgery, Department of Orthopaedic Surgery, Medical School

The balance of bone formation and resorption is regulated by a number of factors including the level of mechanical load the bone experiences.  We are interested in the molecular mechanisms by which this mechanical load is sensed and translated in to a biochemical signal and subsequent biologic response.   This process is studied both in tissue culture cells with in vitro loading systems as well as in vivo.  The laboratory is particularly interested in the role of the Wnt pathway and in LRP 5 and 6 signaling.   

Richard A. Miller, M.D., Ph.D.
Professor of Pathology, Associate Director of the Geriatrics Center, and Research Scientist at the Ann Arbor DVA Medical Center

The Miller laboratory studies the genetics and cell biology of aging in mice. Topics under study include signal transduction in T cells from old donors, genetic analysis of longevity and age-sensitive traits, gene expression analysis of long-lived mutant mice, and investigations of agents alleged to slow the aging process. Collaborations with Bone Center colleagues include quantitative trait locus gene mapping studies of mouse femur and vertebral morphology and function, including studies of the correlations between endocrine levels, muscle strength, and bone properties in a genetically heterogeneous mouse population.

More information can be found at the laboratory web page: http://www-personal.umich.edu/~millerr/RAM_home_page.htm

Michael D. Morris, Ph.D.
Professor of Chemistry, Department of Chemistry, College of Literature, Science, and the Arts.

Dr. Morris’ research program focuses on the interface between chemistry and physics and has two major areas of investigation.  The first relates to enhanced development in capillary gel electrophoresis and the second in the use of Raman spectroscopy as a mode to characterize biologic structures.  Dr. Morris has been particularly productive in developing methodologies for determining properties of mineral and extracellular matrix interactions in bone by using Raman imaging.

Kenneth J. Pienta, M.D.
Professor of Internal Medicine and Professor of Urology, Medical School

The Pienta laboratory focuses on gaining insight into the biologic mechanisms underlying prostate cancer metastasis.  These insights have been used to identify novel targets for the treatment of advanced prostate cancer, thus successfully moving bench research into the clinic in the form of Phase II and Phase III clinical trials.  This research has been developed based on a comprehensive theory of metastasis focusing on the cellular traits necessary for the cancer cell to leave the primary tumor environment (emigration), survive in the circulation (migration), and develop in a secondary site (immigration). Dr. Pienta has developed several therapeutic strategies based on this theory, including targeting cell motility, cell – endothelial attachment, and bone microenvironment – prostate cancer cell interactions.  As noted earlier, Dr. Pienta is part of the team of investigators studying the mechanisms associated with skeletal metastases in prostate cancer.

Bruce C. Richardson, M.D., Ph.D.
Professor of Internal Medicine, Division of Rheumatology, Medical School

This laboratory studies the role that DNA methylation and chromatin structure play in regulating immune and cellular function, and how changes in chromatin structure contribute to the immune and other problems characterizing human lupus and aging. Current studies include analysis of methylation patterns by bisulfite sequencing, analysis of histone modifications by chromatin immunoprecipitation, detection of permissive configurations with DNaseI hypersensitivity assays, and identification of mechanisms regulating DNA methylation and chromatin structure.

Helena H. Ritchie, Ph.D.
Assistant Professor of Dentistry, Department of Cariology, Restorative Sciences and Endodontics, School of Dentistry

Dr. Ritchie’s research focuses on two major dentin noncollagenous proteins: dentin sialoprotein (DSP) and phosphoporyn (PP), which are encoded within a single DSP-PP transcript. Their appearance is coupled to the conversion of uncalcified predentin to calcified dentin and PP in particular is believed to participate in the initiation and control of hydroxyapatite formation. Mutations in the DSP coding regions are linked to dentinogenesis imperfecta I and II, a defective dentin disease affecting 1 in 7000 newborns. DSP-PP expression is tightly restricted to odontoblasts and preameloblasts, although a small amount of DSP protein has been detected in bone.  They are currently defining DSP-PP transcript expression and DSP/PP protein function in dentin mineralization. The long-term goal is to better define the fundamental molecular/genetic processes contributing to odontoblast differentiation, function and dentin mineralization and to apply this knowledge to better facilitate tooth regeneration, and to possibly correct defective dentin mineralization diseases such as dentinogenesis imperfecta II.

Blake J. Roessler, M.D.
Associate Professor of Internal Medicine-Rheumatology; Adjunct Associate Professor of Pharmacy.

Dr. Roessler is in his 13th year as a faculty member and has also been an active Adjunct faculty member in the Department of Pharmaceutical Sciences. For the past 10 years Dr. Roessler has served as the Director of the Human Applications Laboratory, a clean-room facility housed and supported by the NIH-sponsored General Clinical Research Center. This facility is used for the manufacture of protein, cell and tissue-based experimental biological products that are used for Phase I human clinical trials.

Dr. Roessler’s personal research laboratory is located in Medical Science Research Building II and employs two technicians and one post-doctoral fellow. Dr. Roessler has a broad-based research program that is exploring many facets of chondrocyte biology. One research project focuses on defining the patterns of gene expression in articular chondrocytes as a function of age and articular injury. The goal of this project is to identify molecular mechanisms associated with early osteoarthritis that may be targets for drug discovery. The project will also attempt to identify OA susceptibility gene candidates in canine pedigrees with a high incidence of spontaneous OA. In a correlate study Dr. Roessler and collaborators are exploring the use of Raman spectroscopy to identify early structural changes in extracellular matrix components of cartilage that may function as OA biomarkers. A second project is exploring the role of intra-articular adipocytes (fat cells) on chondrocyte biology and extracellular matrix structure.

Theodora S. Ross, M.D., Ph.D.
Assistant Professor of Internal Medicine, Medical School

One component of Dr. Ross’s lab focuses on understanding the transforming biology of HIP1/PDGF'R by creating HIP1/PDGF'R knock-in mice and characterizing the substrates for the HIP1/PDGF'R tyrosine kinase that are necessary for transformation.  They are also interested the HIP1 protein family and its role tumorigenesis and clathrin mediated trafficking. The protein structures of HIP1 and HIP1-related (HIP1r) together with recent data suggest that these proteins link clathrin mediated trafficking and phosphatidylinositol turnover. Using mutational analysis the lab is analyzing how various domains of these proteins contribute to their function in clathrin mediated endocytosis.  They generated mice deficient in HIP1.  HIP1-/- mice displayed defects in hematopoiesis and spermatogenesis where restricted progenitors were defective and as a result underwent accelerated apoptosis.  This suggests that HIP1 is necessary for survival of progenitors at specific stages of development in multiple tissues. However, HIP1 is expressed in multiple cell types but only a subset of these cell types was affected by HIP1 deficiency. Therefore, some lost HIP1 functions may have been compensated for by HIP1r. We are in the process of generating HIP1r deficient mice to test this.  The phenotype included a number of skeletal changes that are being investigated.

Robert U. Simpson, Ph.D.
Professor, Department of Pharmacology, Medical School.

Dr. Simpson’s research interests focus on the actions of vitamin D in the regulation of proliferation of various cells.  He is a relatively new investigator to the bone research field.  His interests stems from vitamin D affects on the osteoclast precursor HL-60 cell.  Most of his work to date related to bone involves the evaluation of vitamin D analogs for the treatment of proliferative diseases such as bone cell cancers and others.  His most recent work has shown that vitamin D suppresses c-myc expression, and he continues to study a series of binding proteins that appear to be involved in the inhibition of c-myc expression.

MaryFran R. Sowers, Ph.D.
Professor in Epidemiology, Adjunct Professor of Obstetrics and Gynecology, Adjunct Professor of Internal Medicine

A primary research focus is the elucidation of the natural history of bone mineral acquisition, maintenance, and subsequent loss leading to fracture and functional limitations in populations. This focus has encompassed studies of the role of reproduction (including pregnancy and lactation), human genetics, menopause and aging. These studies have incorporated detailed endocrinological evaluation of the vitamin D axis and the steroid hormone axis as well as markers of the inflammatory processes.

A parallel research focus involves the evaluation of structural, mechanical, and metabolic attributes of joints and their constituent components, bone, cartilage, muscle, and collagenous materials as changes in these attributes lead to arthritis and compromised functioning in populations. Again, these studies have incorporated detailed endocrinological evaluation of the steroid hormone axis, the genetics of steroid hormones and collagens, assessment inflammatory processes as well as contemporary imaging ranging from MRI to NMR.

Collectively, the research study program represents an integrated approach to issues in women’s health. For example, there is an examination of how the steroid hormone pathway and the attendant subgroups, defined by selected genotypes, are not only related to menstrual cycle characteristics predictive of polycystic ovary syndrome, but also earlier loss of bone or earlier risk of heart disease (in the later instance, though the relationship with thromboembolic factors). Currently funded research evaluates how variation in estrogen metabolites and steroid hormones arises from differences in diet, smoking, and physical activity, and ultimately, how this variation may be related to risk of developing obesity, bone loss, altered lipid profiles, compromised inflammatory profiles, and impaired cognition during the menopausal transition.

Russell S. Taichman, D.M.D., D.M.Sc.
Associate Professor in the Department of Periodontics, Prevention & Geriatrics, Director of the University of Michigan Dental Honors Program.

His research is focuses on the role of osteoblasts in normal bone marrow function. Currently he is trying to identify those osteoblast-derived factor(s) used by osteoblasts to support hematopoiesis using laser capture, cell and animal based systems. It is believe that identifying these mechanisms will ultimately reduce the morbidity/mortality associated with bone marrow transplantation.

In the second but related project, he is studying the mechanisms used by tumor cells to metastasize to the bone marrow. He has found that part of the mechanism relates to products secreted by osteoblasts and endothelial cells in the bone marrow interacting with receptors on tumor cells. The Taichman lab is using a prostate cancer model for a bone homing tumor, that the receptor CXCR4 (an HIV co-receptor) facilitates chemotaxis of prostate cancers towards stromal derived factor-1 (SDF-1). Recently it was observed that blocking CXCR4 resulted in less tumors in animals. In collaboration with Drs Cooney and Julie Douglas at the University of Michigan Cancer Center, the group is exploring single nucleotide polymorphisms in SDF-1 or CXCR4 in men with prostate cancer to identify a link between metastasis and the marrow microenvironment.

In his third project, in collaboration with Dr. Paul Krebsbach, Dr. Taichman is trying to identify osteoprogenitor cells from bone marrow stromal cells (BMSCs) using an in vivo system.

More Information: http://www.dent.umich.edu/research/ccr/

Catherine Van Poznak, M.D.
University of Michigan Comprehensive Cancer Center

Dr. Van Poznak's research concentration is on breast cancer and its relationship with bone. There are three major issues that she researches and  has ongoing clinical trials and collaborative laboratory research efforts underway.

Osteoporosis as it effects women with breast cancer - Due to the prevalence of low bone mass in the general US population, and the frequency at which women are diagnosed with breast cancer, these two diseases commonly overlap. Dr. Van Poznak is exploring the diagnosis, treatment and the prevention, of osteoporosis in patients with breast cancer. She has clinical trials studying the effects  of chemotherapy and aromatase inhibition on bone.

Breast cancer biomarkers predictive of site specific relapse - She is  collaborating with Joan Massague of Sloan-Kettering Cancer Center and with Ingunn Holen of the University of Sheffield to explore biomarkers.

Bone metastases - Dr. Van Poznak is interested in management of bone metastases and anticipate clinical trials exploring novel therapies. She has been involved in clinically exploring toxicities of bisphosphonate therapy (osteonecrosis of the jaw & atypical fractures).

Hom-Lay Wang, D.D.S.
Professor of Dentistry, Department of Periodontics/Prevention/Geriatrics, School of Dentistry

Dr. Wang’s research interests are focused on the use of bone morphogenic proteins in the repair, regeneration and healing of oral mineralized tissues.  Dr. Wang’s long-term objectives are to enhance guided tissue regeneration through the use of these growth factors and tissue engineered constructs.

Stephen J. Weiss, M.D.
E. Gifford and Love Barnett Upjohn Professor, Department of Internal Medicine and Oncology: Chief, Department of Molecular Medicine and Genetics, Medical School

Dr. Weiss is a relatively new investigator in the musculoskeletal field.  He is obviously a very well established senior investigator faculty member and Division Head of Molecular Medicine. While he has an extensive research program, a portion of his research relates to understanding the conditions that stimulate the recruitment and activity of macrophage-like cells.  As a result of this work, he has a significant interest in osteoclasts and factors that control their ability to site select.  Dr. Weiss is also interested in factors that promote or inhibit angiogenesis and how local mechanical forces might influence these processes.

Milford H. Wolpoff, Ph.D.
Professor of Anthropology, and Adjunct Associate Research Scientist, Museum of Anthropology, University of Michigan

Dr. Wolpoff is a paleoanthropologist, which he takes to mean an anthropologist who studies the human past.  He has been in the anthropology department since 1971, a professor since 1977.  Wolpoff was trained at the University of Illinois, a student of Eugene Giles and a product of an aggressively 4-field department.  Beyond anthropology, his training has been in physics and evolutionary biology and ecology.  He brings to the study of the human and non-human primate fossil record a background that combines evolution theory, population genetics, and biomechanics. With over 50 grants funded by the National Science Foundation, National Academy of Sciences, and various other sources including significant support from the University of Michigan, Wolpoff has visited the museums where human and primate fossils are stored and has studied in detail and at length all the materials addressing the fossil evidence for human evolution across Europe, Asia, and Africa.  His research foci have included the evolution and fate of the European Neandertals, the role of culture in early hominid evolution, the nature and explanation of allometry, robust australopithecine evolution, the distribution and explanation of sexual dimorphism, hominid origins, the pattern and explanation of Australasian hominid evolution, the contributions and role of genetics in paleoanthropological research, and the taxonomy of the genius Homo.  In addition, he is a primary describer of many hominid fossil remains.  Drawing on this background and research experience, Wolpoff’s key and continuing research for the last 15 years has been the development, articulation, and defense of his Multiregional model of human evolution. Almost as time consuming has been the preparation and publication of the 2nd edition of Paleoanthropology (1999, McGraw-Hill), Wolpoff’s detailed 878 page presentation of the fossil record for human evolution and the many levels of explanation for the pattern it reflects.  Writing with Rachel Caspari, their Race and Human Evolution (1997, Simon & Schuster) was very favorably reviewed in professional journals and in the New York Times, where it was recommended reading.  It received the W.W. Howells Book Prize in Biological from the Biological Anthropology Section of the American Anthropological Association. Besides these Wolpoff has published 5 other books, 155 papers, and 22 book reviews, has presented numerous lectures and meetings papers, and has had many interviews and video appearances.  Since 1976 Wolpoff has graduated 14 Ph.D. students, 7 women and 7 men, all but two of whom have academic positions.  These Michigan graduates include the discoverer of several new australopithecine species, the first paleoanthropologist to debunk the hominid status of Ramapithecus, the leaders in the study of late Pleistocene European evolution, paleoanthropologists who publish in population genetics, three past or present chairs (or heads) of anthropology departments, and the past president of the American Association of Physical Anthropologists, and the editor of the American Journal of Physical anthropology.  Wolpoff is a member of many anthropological organizations, and is a Honorary Life Member of the Honor Society of Phi Kappa Phi and a Fellow of the American Association for the Advancement of Science

Dr. Wolpoff’s web site: http://www-personal.umich.edu/~wolpoff/

Guozhi Xiao, M.D., Ph.D.
Assistant Research Scientist, Department of Periodontics/Prevention and Geriatrics, School of Dentistry

Dr. Xiao’s research is focused on signal transduction pathways and transcription regulation in osteoblasts, cells that produce and mineralize the extracellular matrix of bone, and is applying this knowledge to improve clinical treatment of osteoporosis and other bone-related diseases in the future. Specific projects include studies to elucidate the mechanism mediating the bone anabolic action of parathyroid hormone (PTH), a potent stimulator of bone formation. This project is specifically focused on how PTH controls the activity of the bone-specific transcription factors such as ATF4 and RUNX2.   He is also evaluating the role of RUNX2 phosphorylation by MAPK in regulation of osteoblast-specific gene expression and bone formation.