Upchurch Lab at the Jobst Vascular Research Laboratory

Dr. Upchurch's research focus is on the mechanisms involved in the development of aortic aneurysms. His most recent grant funding is related to the role of nitric oxide in MMP dependent vessel wall remodeling, particularly the activation of matrix metalloproteinases during aneurysm formation.

Modulation of Nitric Oxide Alters MMP Expression by Vascular Smooth Muscle and Endothelial Cells.
Investigators: Gilbert R. Upchurch, Jr., MD, John W. Ford, BA, James C. Stanley, MD
Funding: National Institutes of Health KO8 and Lifeline Foundation

The purpose of this study is to better characterize the role of nitric oxide, known to be important in vessel wall remodeling, on matrix metalloproteinase (MMP) expression both in vitro and in vivo. MMPs are a superfamily of enzymes that play a role in a number of disease processes including aneurysm formation, rheumatoid and osteoarthritis, and angiogenesis. Data has demonstrated that decreases in nitric oxide lead to a selective increase in MMP-9 production. Further characterization of this in vitro finding is ongoing in the elastase perfused aortic aneurysm model.

Differences in MMP Expression in the Thoracic and Abdominal Aorta in Male and Female Rats
Investigators: Gilbert R. Upchurch, Jr., MD, John W. Ford, BA, Karen Roelofs, DVM, and James C. Stanley, MD
Funding: National Institutes of Health and Lifeline Foundation

Our laboratory is focused on MMP-9, an enzyme felt to be critical in the development of AAAs. We are exploring transplantation of the thoracic and abdominal aorta in rats. Also, using an elastase perfusion model, we have examined differences between males and females rodents and their ability to generate aneurysms. Ongoing experiments using the elastase perfusion model to examine the role of various glycoproteins in knockout mice will be performed.

Surgical Outcomes Research Team (SORT)
Investigators: Gilbert R. Upchurch, Jr., MD, Justin B. Dimick, MD, John A. Cowan, Jr., MD, Peter K. Henke, MD, James C. Stanley, MD
Funding: Internal

We have developed an interest in outcomes research which has extended to cover the breadth of all of General Surgery. Through these studies, we have shown the effects of hospital volume on abdominal aortic aneurysm repair, aortofemoral bypass, thoracoabdominal aneurysm repair, as well as carotid endarterectomy. In addition, general surgical procedures, including hepatic and pancreatic resection, have also been examined. The data available to us spans 13 years from the National Inpatient Sample (NIS). The NIS allows us to examine mortality as a primary endpoint following various surgical procedures across the United States

Doxycycline in Patients with Abdominal Aortic Aneurysms (UMHS)
Investigators: Gilbert R. Upchurch, Jr., MD, James C. Stanley, MD
Funding: National Institutes of Health (pending)

We hope to participate in a NIH-sponsored multicenter trial which seeks to examine the effects of doxycycline, a known nonspecific MMP inhibitor, on aneurysm growth in patients with small nonoperable abdominal aortic aneurysms (AAAs). This trial is closely linked with an internal trial in our General Clinical Research Center, which has been examining the effects of doxycycline in patients with large nonoperative AAAs.

The Role of COPD in Patients with Abdominal Aortic Aneurysms: The Influence on COPD on Length of Stay and Mortality.
Investigators: Gilbert R. Upchurch, Jr., MD, Mary C. Proctor, MS, James C. Stanley, MD
Funding: Internal

Over the last ten years at the University of Michigan, data has been accrued on all patients undergoing abdominal aortic aneurysm repair. A special focus has been placed on patients with chronic obstructive pulmonary disease. A database is presently in place that examines the influences of medications such as steroids and inhalers on morbidity, length of stay, and mortality. In addition, a large Veterans Administration database is being incorporated in order to increase the significance of this study.

INVESTIGATIONAL TRIALS

2002 Co-investigator A Phase I, open label, single dose, roll-over, multi-center study of Ad/Hypoxia inducible factor (HIF)-1α/VP16 gene transfer administered by intramuscular injection to patients with critical limb ischemia who are not candidates for surgical or percutaneous revascularization (protocol #PVD-HIF-003-99)

2003 Co-investigator The Valor Trial. Evaluation of the Medtronic AVE Talent Thoracic Stent Graft System for the Treatment of Thoracic Aortic Aneurysms