Grants We Funded

Abstract
The majority of chronic wounds occur in people over age 60, significantly impacting their quality of life. Many studies support that an imbalance between matrix metalloproteinases (MMPs) and tissue inhibitor of metalloproteinase (TIMPs) results in degradation of the extracellular matrix and impaired wound healing. Induction of MMP expression by reactive oxygen species (ROS) has been reported to be mediated by mitogen-activated protein kinases (MAPKs) in vitro, but the interaction between ROS and MMPs in vivo has not been explored. Using a young rat ischemic wound model, we found both high ROS production and MMP expression in the ischemic wound, which correlated with high levels of phosphorylated MAPKs. Based on these preliminary results, we hypothesized that the ROS/MAPK/MMPs/Apoptosis pathway plays a key role in chronic wounds in the elderly. To test this hypothesis we have modified the previously utilized random ischemic flap wound to one with axial blood flow. This allows us to selectively and accurately deliver MAPK siRNA to the ischemic wound tissue via the axial artery. Using this novel animal model in aged rats, combined with special inhibitors delivered locally, we will elucidate whether the following three imbalances exist in the aged ischemic wound: 1) imbalance between removal and production of ROS; 2) imbalance between MMPs and TIMPs; and 3) imbalance between cell proliferation and apoptosis. The use of MAPK siRNA will then allow us to determine the relationship between those imbalances and MAPK signaling. This research is intended to delineate the cellular and molecular mechanisms that result in chronic wounds so that rational therapies can be developed to improve healing in the elderly.

Biography
Qixu Zhang, MD, Ph.D, is an Assistant Professor in the Department of Plastic Surgery at University of Texas MD Anderson Cancer Center. He is an active member of PSRC, WHS, SFB, TERMIS and SPRBM. Dr. Zhang received his Medical Doctorate degree from Nanjing Medical University in China. He completed orthopedic surgery and microsurgery residency at an affiliate hospital of BinZhou Medical College. After that, Dr. Zhang continued his education at Peking Union Medical College, where he received PhD degree in Surgery. Dr. Zhang was formally trained in plastic surgery at the Plastic Surgery Hospital of Peking Union Medical College, the top one plastic surgery institution in China. Dr. Zhang then pursued a postdoctoral fellowship in Plastic Surgery at the University of Texas Medical Branch in Galveston. He continued his postdoctoral training in Plastic Surgery at the University of Texas MD Anderson Cancer Center in Houston. After completing his fellowship, Dr. Zhang joined the research faculty in Plastic Surgery at MD Anderson Cancer Center. Dr. Zhang has published over 40 scholarly articles, and is the editor and/or author of five books. He has presented his research over forty times at the international and national conferences. His research focuses on the biomaterials, tissue engineering, and wound healing, inflammatory fibrosis. In his free time, Dr. Zhang enjoys playing tennis and practicing Chinese Calligraphy.