Research Focus

Dr. Yejia Zhang evolves into an independent investigator

Yejia Zhang, MD, PhD, was recruited to Penn PM&R as an academic physiatrist in 2013. Her clinical and academic career has focused on the degenerating intervertebral spinal disc. She currently is an Assistant Professor of Physical Medicine and Rehabilitation on the Clinician Educator track.

Dr. Zhang trained medically at the Second Military Medical University based in Shanghai, China. She received a PhD in cell and molecular biology from Penn in 1997. In 2002, she graduated from the residency training in Physical Medicine and Rehabilitation at the University of Rochester School of Medicine and Dentistry in Rochester, NY. Between 2002 and 2006, she participated in the National Institutes of Health’s Rehabilitation Scientist K12 Fellowship Training Program while she was based within the Department of Orthopaedic Surgery at the Rush Medical College at Rush University in Chicago, IL. She was employed in the Department of Physical Medicine and Rehabilitation at the Thomas Jefferson University in Philadelphia between 2006 and 2008, and then she returned to Rush in Chicago in 2008 where she held dual academic appointments in Physical Medicine and Rehabilitation and Orthopaedic Surgery before joining the Penn PM&R faculty in 2013. While at Rush, she was funded by a National Institutes of Health’s (NIH) Mentored Clinical Scientist K08 Development Award to investigate cell therapy for degenerating intervertebral spinal discs as mentored by orthopaedic spinal surgeon, Howard S. An, MD, renown for research investigation in tissue engineering of the spinal intervertebral disc.

Since coming to Penn, she has been funded as the principle investigator for pilot investigations as awarded by several funding sources including the North American Spine Society, the NIH-funded Penn Center for Musculoskeletal Disorders based within Penn Orthopaedic Surgery, and the Department of Veterans Affairs. Current pilot funding includes a Small Projects in Rehabilitation Research or SPiRE Program Award from the Department of Veterans Affairs, a NIH’s Institute for Arthritis and Musculoskeletal and Skin Disorders R21 grant, and a Competitive Career Development Fund grant from the Veterans Integrated Service Network or VISN-4 within the Department of Veterans Affairs.

Dr. Zhang’s current translational investigation has pursued elucidating the mechanisms by which spinal discogenic disease causes lower back pain. This has encompassed exploration of the pro-inflammatory roles of the intervertebral disc and the extracellular disc matrix and fibronectin fragments in modulating degenerative disc-related axial lower back pain. Her line of investigation entails defining the gene expression profiles of the intervertebral disc, specifically of the pro-inflammatory cytokine inhibitor, a-disintegrin and metalloproteinase-8 or Adam-8. Elaboration of these genetic profiles would then underpin the development of cell-based gene therapies and stem cell therapies to treat degenerating intervertebral spinal discs. During her career, Dr. Zhang has had access to animal (cow, rabbit, goat and mouse models) and human intervertebral disc tissues to perform her research.

Currently, her mouse model elaborates the early stages of intervertebral disc degeneration, not well understood in humans. By identifying the intradiscal factors that precipitate early inflammation and induce repair, it is thought that these factors could be manipulated as a strategy to reduce disease progression in animals and in humans, and/or reduce associated lower back pain in humans. More specifically, modifications in the gene expression of Adam-8 could be developed. Adam-8 is upregulated in the degenerated intravertebral disc in both mice and humans, and modifications of Adam-8’s proteolytic functions could be developed resulting in inhibition of disc degeneration.

Dr. Zhang has acquired wet bench laboratory space in the Medical Research Building at the Corporal Michael J. Crescenz Veterans Affairs Medical Center in Philadelphia. Her lab is an integrated component of the Translational Musculoskeletal Research Center under the direction of Dr. Robert L. Mauck, Professor of Orthopaedic Surgery and Professor of Bioengineering, at Penn. As a member of this research center that focuses on musculoskeletal regeneration, Dr. Zhang has collaborated closely with other members of this center as a co-investigator, including Harvey E. Smith, M.D., an academic orthopaedic spinal surgeon who is funded by a Veterans Affairs Merit Award to develop advanced tissue-engineered total disc replacement in a large animal model, and Lachlan J. Smith, Ph.D., a neurosurgical basic scientist, who is funded by the NIH’s Institute of Arthritis and Musculoskeletal and Skin Diseases to investigate the regenerative potential of the embryonic notochordal cells within the primitive spinal cord and vertebral column. Dr. Zhang also collaborates with Ling Qin, Ph.D., Associate Professor of Orthopaedic Surgery at Penn, focusing on fracture repair. Dr. Zhang been the recipient of multiple awards that recognize her scientific pursuits including the North American Spine Society Basic Science Award in 2013, the American Academy of Physical Medicine and Rehabilitation’s President’s Citation Award for Outstanding Research in 2007, and the New Investigator’s Award of the Education and Research Foundation of the American Academy of Physical Medicine and Rehabilitation in 2005. She has collaboratively published up to fifty peer-reviewed journal articles; she was first or senior author in up to twenty of these publications.

An excellent summary of her collaborative investigative approach had been published earlier this year: Tain, Z., Ma, X., Yasen, M., Mauck, R.L., Qin, L., Shofer, F.S., Smith, L., Pacifici, M, , Enomoto-Iwamoto, M., Zhang, Y. Intervertebral disc degeneration in a percutaneous mouse tail injury model. American Journal of Physical Medicine and Rehabilitation 2018;97:170-177.