Candidate: Dr. Bragdon's training has been multidisciplinary encompassing biochemistry, molecular biology, and biophysics. During her research career she developed an interest in skeletal biology which she furthered by joining Dr. Gerstenfeld's lab and moving these interests into in vivo bone repair and regeneration models. Dr. Bragdon's long term goal is to become an independent researcher in an academic environment, pursuing basic and applied research in skeletal tissue biology to identify mechanisms that can be exploited as treatment for heterotrophic ossification, to advance current bone grafting materials, and to improve bone regeneration. In order to obtain these goals a career development plan has been developed by Drs. Gerstenfeld and Morgan, along with a co-mentor committee who will assist Dr. Bragdon as she transitions to an independent career. The mentor committee consists of both basic scientists and clinicians who will be able to provide clinical perspectives, interdisciplinary knowledge base, and independent advice. During this time additional research skills will be learned, specifically Fluorescence Activated Cell Sorting and microarray analysis. Equally balanced with learning of new technical skills will be professional development which is based on the National Postdoctoral Association Core Competencies and includes: communication, leadership and management, discipline-specific conceptual knowledge, professional skills, and responsible conduct of research. Resources available at Boston University will greatly aid in the career development of Dr. Bragdon. She will have access to core facilities run by faculty and staff members for technical advice, professional development through the Office of Professional development and Post-doctoral Affairs, BU Broadening Experiences in Scientific Training (BEST), Women in Science and Engineering, and Women in Networks. Research: Fractures are one of the most traumatic injuries that can occur in humans with 8 to 10 million fractures occurring annually which approximately 10% results in delayed or impaired healing. Repair is dependent upon the recruitment of mesenchymal stem cells (MSCs) to the injury site followed by a cascade of events resulting in the formation of cartilage and bone. A similar event can also occur in soft tissue due to trauma, burns, and total hip replacements resulting in boney tissue called ectopic or heterotopic ossification (HO). Multiple stem cell populations from the bone surface and muscle have been suggested to be involved however it is unclear as to the specific population of skeletogenic stem cells that are recruited or their location. Based on previous data the hypothesis of this proposal is that there i a universal MSC with in the axial limb tissues that contributes to injury induced bone formation.
The aims of this proposal will 1) determine the stem cell contribution from the bone surface and muscle to the HO and identify whether the stem cell populations are similar, 2) determine the impact of muscle trauma has on the populations of recruited stem cells, and 3) determine the transcriptional machinery of these stem cell populations. In this proposal demineralized bone matrix will be implanted into inducible transgenic reporter mice models to induce ectopic bone formation. The mouse models will allow for the specific labeling and capturing of the different populations of cells known to induce during fracture and ectopic bone formation.

Public Health Relevance

Post-natal bone formation is dependent upon a group of stem cells that are capable of differentiation into the mature cells of skeletal tissues. These stem cels have been reported to be located in various locations, including muscle and surrounding tissue of the bone. This proposal aims to identify the origin of these cells and whether they are similar independent of their location.

Agency
National Institute of Health (NIH)
Institute
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Type
Career Transition Award (K99)
Project #
5K99AR068582-02
Application #
9288127
Study Section
Arthritis and Musculoskeletal and Skin Diseases Special Grants Review Committee (AMS)
Program Officer
Wang, Fei
Project Start
2016-06-06
Project End
2018-05-31
Budget Start
2017-06-01
Budget End
2018-05-31
Support Year
2
Fiscal Year
2017
Total Cost
$90,180
Indirect Cost
$6,680
Name
Boston University
Department
Orthopedics
Type
Schools of Medicine
DUNS #
604483045
City
Boston
State
MA
Country
United States
Zip Code
02118