Yejia Zhang,  MD,  PhD

Dr. Yejia Zhang is a dedicated physician-scientist interested in intervertebral disc (IVD) degeneration and repair. Back pain related to IVD degeneration is an important cause of morbidity among Veterans, with limited therapeutic options. Her research on IVD repair has been supported with a K08-award by the NIH. There is a nice synergy between her clinical work caring for patients with spine-related pain and research focused on the mechanisms of intervertebral disc degeneration and repair. She currently devotes 50% of time to spine-related research, and 50% effort to patient care and teaching. With a doctoral training focusing on collagen gene regulation and clinical experience of back pain management, she is well suited to bringing findings at the lab bench to patient care. In addition, she is the first Physiatrist in the Philadelphia VA Medical Center and Department of Rehabilitation at Penn to pursue wet lab research. This endeavor may encourage other Physiatrists to follow, thus forming a critical mass for evidence-based medicine in the field of Physical Medicine and Rehabilitation.

In particular, her team was initially interested in fibronectin fragments because they were potent initiators of IVD degeneration. Subsequently, they identified ADAM8 as a fibronectin-cleaving enzyme, and have shown that fibronectin N-terminal fragments increase with IVD degeneration in human tissues. These experiments establish the clinical relevance of ADAM8. Further experiments in the mouse, especially in the novel ADAM8-inactivation mouse, will delineate molecular mechanisms of ADAM8 action. This project has strengthened her existing collaborations with Motomi Enomoto-Iwamato because both ADAM8 and fibronectin interact with integrin, a long time interest of Dr. Iwamoto's. Dr. Iwamoto has reagents and established techniques to examine molecular interactions between integrin and ADAM8. Dr. Iwamoto has generously shared her resources including reagents and methodology used in tendon, joint and bone, resulting in cross fertilization of the intervertebral disc field.

Since Dr. Zhang returned to Penn four years ago, she has also formed new collaborations with Robert Mauck, PhD. Their teams currently occupy a shared laboratory within the Translational Musculoskeletal Research Center (TRMC) at the Philadelphia VA Medical Center (VAMC). His background in engineering and Dr. Zhang's training in biology and clinical experience generate synergies: they are examining bone-disc-bone motion segments biomechanical properties in mice with various molecular modifications. Together the will work towards a common goal: to understand the mechanism of disc degeneration and help patients with back problems.

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