Laboratory of Tissue Repair
VCU Medical Center
1101 E. Marshall Street
Richmond, Virginia 23298-0614 United States
Contact: Bob Diegelmann
Description: The major research interest of this Laboratory of Tissue Repair is focused upon the signaling events that occur during tissue injury, shock and repair. Following injury, an orderly sequence of events is initiated to begin the healing process. The first stage begins at the time of injury when local environmental factors such as low oxygen tension, lactate accumulation, cell debris, and foreign materials serve as attractants to bring inflammatory cells to the area. Peripheral blood cells trapped in the clot and growth factors released from platelets play critical roles to initiate the repair process. Neutrophils are the first inflammatory cells to arrive at the wound site. As tissue macrophages are attracted to the area, chemical signals are sent out to stimulate the fibroblasts in the surrounding tissue to migrate to the site of injury and to proliferate. Several days following injury, the expanded population of fibroblasts becomes intensely active in synthesizing new extracellular matrix. During latter stages, the cells are engaged in a continuing process of wound remodeling. Biochemical observations made in the dermal repair models provide valuable clues to understanding the regulatory mechanisms involved in tissue repair throughout the body. When too much scar tissue is deposited, then the many clinical problems associated with fibrosis are seen such as keloids, hypertrophic scars, strictures, adhesions, liver cirrhosis and Crohn's disease. In contrast, when healing is impaired, chronic pressure, diabetic and venous stasis ulcers can develop. This laboratory has found recently that pressure ulcers contain excessive neutrophils in pressure ulcers that in turn release damaging enzymes such as MMP-8 and elastase that destroy the extracellular matrix and growth factors needed for healing. Strategies are being developed to inhibit the influx of neutrophils into the ulcer site and also to inhibit their destructive enzymes so healing may proceed. Our research studies involve human subjects, animal models and reconstituted tissue culture and cell culture systems. The laboratory has the capacity to examine these clinical problems using state of the art biochemical and molecular biology techniques. In recent years the laboratory's research interests have been expanded and combined with other clinical scientists in the VCU Reanimation, Engineering and Shock center (http://www.vcu.edu/vcures/ ). These new initiatives are focused on combat casualty care and the development of novel strategies to achieve metabolic down-regulation as a mechanism to treat shock in trauma patients. In addition we have recently discovered a novel technology to control severe hemorrhage. This new product is called WoundStat and is being further developed and marketed by TraumaCure. This life-saving technology is applicable in the battlefield as well in the civilian sector to save many lives following trauma. Other studies are focused on the use of Immune-Regulating Hormones such as Androstenediol to optimize the wound healing response in patients where the healing process is compromised. Recently the laboratory received a major grant from the US Army to study Optimization of Wound Healing to Limit Infection. The Laboratory of Tissue Repair has a long history of research and training, dating back to 1972 and currently Dr. Diegelmann is Program Director of a NIH Institutional NRSA to train postdoctoral fellows in the area of tissue repair. Overall the laboratory is engaged in highly translational research to develop new strategies to treat the many clinical problems associated with tissue injury, tissue repair and shock.
Lipid Mediators in Wound Healing
1101 East Marshall Street
Richmond, Virginia 23298 United States
Hours: 6:00 AM-6:00 PM (M-F)
Research Lab Name: Shanaka
Description: My primary research interest is to understand the role of bioactive lipids in the regulation of pathways mediating wound healing events. Accumulating data continue to validate the important role played by signaling lipids in multiple biological processes. These include hemostasis, inflammation, cellular migration and proliferation as well as angiogenesis. All of these processes are also important stages in the wound healing process. The lipids of importance in these processes include the eicosanoids, sphingolipids, steroid hormones as well as various phospholipid species. Until recently these lipids mediators could only be analyzed one or at most a few at a time. The development of atmospheric pressure ionization (API) tandem mass spectrometry coupled to High/Ultra performance liquid chromatographic (HPLC/UPLC) separation (lipidomics) has enabled researchers to analyze close to the full spectrum of signaling lipids. Due to the complex and interacting nature of the multiple lipid signaling pathways involved in wound healing, it is only a global lipidomic approach such as this that will allow for lipid related disregulations in the wound healing procedure to be investigated. Currently I am actively involved in the development of mass spectrometric methods to investigate the global changes in bioactive lipid profiles as related to wound healing.