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Dr. Ron Alkalay ’s first area of research aims to elucidate the role of vertebral structures, namely, cancellous bone and vertebral cortex, in effecting the mechanism of failure and consequently the post-failure response of thoracolumbar vertebra to complex loading scenarios. In collaboration with the Department of Radiology at BIDMC and the Department of Orthopedic Surgery at the Mayo Clinic in Rochester, Minn., his group is evaluating, under the auspices of an NIH R01 grant, the use of Quantitative CT image-based structural analysis program to classify whether vertebrae with metastasis defects are at risk of premature failure.
The second area of research involves development of novel MR techniques for evaluating the effect of age and degeneration on the mechanical competence of human discs. This work, in collaboration with the Department of Radiology at BIDMC and the Surgical Planning Laboratory at Brigham and Women's Hospital, incorporates the use of Tensor diffusion imaging and novel analysis techniques to provide detailed interrogation of the mechanical properties of the disc. The outcome of this work will allow better classification of disc as candidate for clinical treatment and may offer the possibility of developing novel, non-invasive methods to aid and evaluate the efficacy of new approaches and tissue based treatments for disc disease.
Dr. Mary Bouxsein has been a member of the biomechanics lab at BIDMC since 1992, and currently holds joint appointments as an Assistant Professor of Orthopedic Surgery at Harvard Medical School and adjunct Assistant Professor of Mechanical Engineering at Boston University; she is also a faculty member in the MIT-based Bioastronautics Program. Her research focuses on understanding skeletal fragility from a biomechanics viewpoint, and includes studies using animal models and human cadaveric tissue, as well as clinical investigations. She also has a strong interest in the use of novel non-invasive imaging techniques to predict fracture risk and monitor response to osteoporosis therapies.
Dr. Bouxsein has funding from the NIH to study the etiology of vertebral fractures and the role of bone microarchitecture in skeletal fragility in approximately 3,500 participants in the Framingham Heart Study. She also was awarded an NIH-Challenge grant to study the effects of perinatal diet on bone acquisition and maintenance, and has funding from NASA to study the effects of partial-weight bearing on the musculoskeletal system, and to study the effects of a novel bone anabolic drug in microgravity. Dr. Bouxsein previously served as a board member of the International Bone and Mineral Society, and currently serves on the committee of scientific advisors for the National Osteoporosis Foundation, as well as the International Osteoporosis Foundation. Dr. Bouxsein is an Associate Editor for the Journal of Bone and Mineral Research, and has published more than180 peer-reviewed articles and 30 book chapters and invited reviews. She was recently awarded the Herbert A. Fleisch Medal for scientific contribution to the field of bone biology by the International Osteoporosis Foundation.
Dr. Christopher Evans is primarily interested in translational research leading to the development of novel biological therapies for the treatment of conditions affecting bones and joints. Particular, but not exclusive, emphasis is placed upon the use of cell and gene therapy. There are two main areas of concentration.
The first area is arthritis, where Dr. Evans is developing gene therapy approaches for treating both rheumatoid and osteoarthritis and related conditions, such as pigmented villonodular synovitis. In each case, the strategy is to introduce an appropriate cDNA into the affected joint by intra-articular injection of a viral vector. This research has already resulted in a Phase I clinical trial and additional clinical trials are going through the regulatory process.
The second major area lies in the restoration, repair and regeneration of bone, cartilage and other orthopaedic tissues. Most progress has been made in developing technologies for healing large segmental defects in a rat femoral model. This model responds to cell-based, gene-based and protein-based regenerative methods and present research is devoted to assessing which of these are most appropriate for taking forward into large animal studies as a prelude to possible human trials. Studies of a gene therapy approach in sheep have recently received funding and are pending.
Dr. Ara Nazarianhas been a member of the lab since 1999, first as a Master's student, a PhD student, and now as an Assistant Professor in Orthopedic Surgery at Harvard Medical School. He also holds an appointment as an adjunct Assistant Professor of Biomedical Engineering at Boston University. Dr. Nazarian’s work mainly focuses on basic biomechanics and bioimaging of normal and pathologic cancellous and cortical bone, with emphasis on fracture prediction resultant from local and systemic skeletal pathologies. He has been working on the CT-based Structural Rigidity Analysis (CTRA) methodology for the past eight years along with Dr. Brian Snyder. His efforts on this project include completely redesigning the program for ease of use, increased functionality and high throughput; conducting a multi-center study of breast cancer patients to establish thresholds for prediction; generating normative database for axial and appendicular bones; and conducting a small multi-center study, sponsored by the Musculoskeletal Tumor Society, to compare the efficacy of this method to current clinical guidelines. He has conducted a number of animal studies investigating the efficacy of this technique to assess reduction in bone strength in animals with local and systemic skeletal defects.
From an imaging perspective, as part of his K99/R00 award, he is working on a combined liquid and solid state MR imaging method to differentiate different skeletal pathologies based on changes in bone mineral, matrix and structural components.
Dr. Nazarian, in collaboration with Drs. Arun Ramappa and Joseph DeAngelis, is exploring the hypothesis that scapulothoracic motion (scapular motion relative respect to the thorax) significantly affects superior labral strain. As a result, he and his colleagues propose that superior labral strain is different in an intact specimen, a replicated SLAP lesion and a repaired SLAP lesion in cadaver shoulders. As part of this Major League Baseball-funded project, he has developed unique biomechanical methods to accurately estimate shoulder joint kinematics and is investigating the effects of scapulothoracic positioning on superior labral strain during simulated throwing using in an intact, replicated SLAP lesion, and repaired cadaveric shoulder model.
Dr. Ryan Porter joined the lab in 2008 as a postdoctoral fellow in the Evans lab; in 2011, he became a full-time member of the research faculty. His laboratory investigates ways to direct soft tissue repair or regeneration within the synovial joint in response to traumatic injury or degenerative disease (e.g., osteoarthritis). One early focus area concerns articular cartilage regeneration using adult stem/progenitor cell populations (derived from bone marrow or adipose tissue), studying how the injured joint environment affects regenerative activity following implantation. Specifically, his group is using noninvasive imaging (e.g., bioluminescence, SPECT) to follow the regenerative activities of human progenitor cells upon their implantation into immune-compromised rodent injury models. They are also exploring how to alter the damaged joint environment so as to promote tissue regeneration. For example, pro-inflammatory factors within the injured/diseased joint may inhibit the chondrogenic process and, thereby, progenitor-cell-based regeneration. This work has been supported by a career development award (K99/R00) from the NIH and the Klarman Family Foundation.
Dr. Porter is interested in new collaborations that pursue these clinical goals as well as similar challenges in skeletal regenerative medicine. His group brings to the table expertise in the biology and genetic modification of adult stem cells as well as rodent models of skeletal tissue repair (bone, cartilage, tendon) and intra-articular therapy.
Dr. Brian Snyder is a board certified pediatric orthopaedic surgeon on staff at Boston Children’s Hospital, where his clinical practice focuses on spinal deformity related to congenital and neuromuscular etiologies; hip dysplasia and other acquired deformities about the hip; cerebral palsy; and pediatric trauma.
Dr. Snyder’s research interests include the mechanical etiology of osteoarthritis; etiology and prevention of age-related fractures; etiology and prevention of fracture associated with metastatic defects and benign bone defects; the reciprocal relationship between thoracic and spinal deformity and its effect on pulmonary function; relative interaction of material and structure in normal and pathologic bone; structural and mechanical analysis of tissue engineered bone using micro-computed tomography and mechanical testing.
Dr. Snyder has been associated with the laboratory since its founding in 1979 by his thesis advisor and mentor, W.C. Hayes, PhD He completed his MD and PhD in Biomechanics at the University of Pennsylvania under the auspices of the NIH Medical Scientist Training Program. His PhD thesis evaluated the relationship between trabecular bone structural morphology and material behavior. Since completing his residency training in orthopaedic surgery at Harvard Medical School, Dr. Snyder has forged collaboration between the Orthopaedic Biomechanics Laboratory at Beth Israel Deaconess Medical Center and the Department of Orthopaedic Surgery at Boston Children’s Hospital. This unique partnership has merged the sophisticated analytic techniques developed at the laboratory with the innovative diagnostic and surgical techniques developed at Children’s for treating musculoskeletal diseases.