The trainee is a young physician with a strong basic science background. With the guidance of the rehabilitation scientist training program (RMSTP), she has designed a career path that brings together her scientific and clinical interests. Her research has attracted a considerable amount of positive attention in the field of rehabilitation. Seven full manuscripts resulted from this work: three have been published, one in press (see attached manuscript and letter), and three are in review. In addition, 15 abstracts have been presented at national and international meetings. The proposed research development plan will allow her to gain additional technical expertise under the guidance of seasoned scientists, and become an independent clinician-investigator. ? ? The trainee's research plan addresses an immensely important clinical problem, back pain. Although the etiology of back pain is most likely multi-factorial, intervertebral disc degeneration is perhaps causally associated with back pain. Biological treatment with a growth factor may promote matrix repair and restore physiological function. Cell-based gene therapy, which aims at the sustained release of growth factors, will be explored. ? ? This revised proposal contains new data further supporting the central hypothesis that cell therapy is likely to represent an effective tool for slowing or even reversing disc degeneration (1) Rabbit intervertebral disc (IVD) explants injected with allogenic rabbit articular chondrocytes transduced with Ad-hBMP-7 produce more hBMP-7 protein, and (2) Rabbit IVD explants injected with articular chondrocytes expressing hBMP-7 accumulate more proteoglycans. Based on these findings, the trainee proposes to study the effects of BMP-7 on degenerative rabbit intervertebral discs using the ex vivo gene transfer method. She has also performed a pilot in vivo study and transplanted allogenic rabbit articular chondrocytes into the degeneration rabbit IVD, demonstrating her ability to perform in vivo studies. ? ? Dr. Irving Shapiro, a disc biologist, has assumed the role of the trainee's primary mentor. Her in vivo study will also be helped by Dr. D. Greg Anderson, a spine surgeon, with extensive experience with the animal disc injury model. In the revised training plan, the trainee proposes to participate in course work and to learn additional techniques. Thomas Jefferson University provides a rich environment, and has a strong commitment to support her career development. ? ? ? ?

Agency
National Institute of Health (NIH)
Institute
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Type
Clinical Investigator Award (CIA) (K08)
Project #
1K08HD049598-01A2
Application #
7212018
Study Section
Special Emphasis Panel (ZHD1-RRG-K (YZ))
Program Officer
Nitkin, Ralph M
Project Start
2007-01-20
Project End
2010-12-31
Budget Start
2007-01-20
Budget End
2007-12-31
Support Year
1
Fiscal Year
2007
Total Cost
$129,546
Indirect Cost
Name
Thomas Jefferson University
Department
Physical Medicine & Rehab
Type
Schools of Medicine
DUNS #
053284659
City
Philadelphia
State
PA
Country
United States
Zip Code
19107
Chandra, Abhishek; Lin, Tiao; Young, Tiffany et al. (2017) Suppression of Sclerostin Alleviates Radiation-Induced Bone Loss by Protecting Bone-Forming Cells and Their Progenitors Through Distinct Mechanisms. J Bone Miner Res 32:360-372
Tian, Zuozhen; Ma, Xiaoyuan; Yasen, Miersalijiang et al. (2017) Intervertebral Disc Degeneration in a Percutaneous Mouse Tail Injury Model. Am J Phys Med Rehabil :
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Zhang, Yejia; Lenart, Brett A; Lee, Joseph K et al. (2014) Histological features of endplates of the mammalian spine: from mice to men. Spine (Phila Pa 1976) 39:E312-7
Anderson, D Greg; Markova, Dessislava; An, Howard S et al. (2013) Human umbilical cord blood-derived mesenchymal stem cells in the cultured rabbit intervertebral disc: a novel cell source for disc repair. Am J Phys Med Rehabil 92:420-9

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