Surgical Research Lab
The development of new blood vessels from pre-existing vessels (angiogenesis) is essential for normal wound healing and is often inadequate in poorly healing wounds. On the other hand solid tumor growth and metastases can be facilitated by angiogenesis. Thus understanding how to accelerate or impair angiogenesis has broad clinical relevance. Dr. Boudreau’s research group has been focusing on how endothelial cells coordinately regulate expression of genes for extracellular matrix proteins, matrix degrading proteinases, and cellular adhesion molecules, which are essential in the development of new capillaries. In particular they are investigating the role of Homeobox (Hox) master transcriptional factors that appear to control expression of many of these genes associated with matrix remodeling during angiogenesis.
The research group has identified Hox genes that can either promote angiogenesis, or those that appear to inhibit this process. Specifically they have shown that Hox D3, Hox A3 and Hox B3 all promote angiogenesis and using a novel gene transfer method, they can accelerate closure of problem diabetic wounds as well as poorly healing wounds in aged tissues. Moreover, the expression of pro-angiogenic genes is dysregulated in diabetic and aged tissues and are exploring how altered mechanical loading of aged skin leads to reduced Hox gene expression. They have also observed that Hox D10 and Hox A5 impair angiogenesis by impairing cell migration and promoting vascular cell differentiation or stability of neovessels respectively. Interestingly, expression of these anti-migratory Hox genes is also lacking in infantile hemangiomas and restoring their expression can stabilize these structures.
Additionally, the research group is investigating whether restoring expression of these vascular stabilizing genes will also prevent development of brain arteriovenous malformations. They have now developed tissue-specific inducible transgenic mice to allow controlled and restricted expression of Hox genes specifically in the endothelium which can be used to study the contribution of Hox genes in mediating vascular stability in tumors and in vascular malformations. They have also begun to examine Hox gene expression during differentiation of embryonic stem cells toward and endothelial lineage. Expression of pro-angiogenic Hox3 genes occurs during the early stages of differentiation whereas maturation of progenitor cells is linked to upregulation of the anti-angiogenic HoxD10 and HoxA5 genes.
The research group is currently developing a variety of means to manipulate Hox gene expression in progenitor cells to improve expansion and grafting of progenitor cells in wounds. In addition, they are exploring the role of the anti-invasive Hox D10 gene in breast epithelial tumors. Restoring expression of HoxD10 in tumorigenic epithelial cells prevents tumor cell growth and invasion and also reduces production of secreted angiogenic factors.
The San Francisco Injury Center for Research and Prevention
The San Francisco Injury Center for Research and Prevention (SFIC) is one of 12 Injury Control Research Centers funded by the National Center for injury Prevention and Control at the Centers for Disease Control and Prevention. The SFIC was established in 1989 and is located at the San Francisco General Hospital campus of the University of California, San Francisco, School of Medicine.
The SFIC is a center without walls - bringing together multidisciplinary faculty investigators from throughout the UCSF campus and beyond. The resulting collaborative efforts in laboratory research, clinical trials and injury prevention research have the potential to improve outcomes for victims of trauma in our region and to influence the field of injury control on a global basis.
SF General Hospital & Trauma Center Wraparound Project
The San Francisco Wraparound Project is now an extension of the Trauma Center's traditional services. The Wraparound Project currently provides mentorship, partners with community organizations and links clients to essential risk-reduction resources in order to reduce injury recidivism and prison recidivism in the citizens of the City of San Francisco, hardest hit by interpersonal and youth violence.
Interpersonal violent injury is now pervasive in the United States, and trauma centers stand on the front lines of the epidemic. According to the Centers for Disease Control WISQARS reports, homicide was responsible for 17,357 deaths in 2004. This represents over 565,000 potential life years lost, giving credence to the concern that interpersonal violence disproportionately affects our young people. Disadvantaged minority populations are disproportionately represented in this devastation. Homicide is the number one cause of death in African Americans aged 10-24 years old and number two amongst Hispanics.
Fatalities from assault represent the tip of the iceberg; non-fatal injuries are believed to outnumber fatal injuries on the order of one hundred to one. Trauma centers, including San Francisco General Hospital, often typify the "revolving door" phenomenon: for many young individuals who are assaulted, over 300 each year at our hospital, violent injury is not a one-time event. Injury recidivists constitute between 10 and 45% of all violence-related admissions nationwide. Many violently injured youth and young adults have a record of criminal activity but are not provided "reentry" opportunities in a like manner to the criminal justice system. For many of these individuals, they are not ushered towards these opportunities simply because they ended up on the wrong end of the weapon. In addition, physical rehabilitation is provided in the aftermath of injury, however, providing services to reduce or eliminate risk factors associated with violent injury and criminal activity are not traditionally offered upon hospital discharge.