Current Research Profiles

P-selectin is Central to Venous Thrombosis Pathogenesis

Investigators: Thomas Wakefield, MD (PI), Daniel Myers, Jr DVM, MPH, Peter Henke, MD

The project evaluates the role of P-selectin, platelet-derived microparticles, and leukocyte-derived microparticles in the pathogenesis of venous thrombosis.

Prospective Investigation of Pulmonary Embolism Diagnosis II

Investigators: Paul Stein MD (PI), Jack Weg MD (PI, Pulmonary Medicine, Subcontract), Thomas W. Wakefield MD (Ultrasound Chair)

Funding: National Institutes of Health

The project compares spiral CT scanning to pulmonary angiography diagnosis of pulmonary embolism.

Aging Venous Thrombi with Ultrasound Elasticity Imaging

Investigators: Jon Rubin MD (PI, Radiology), Stanislav Emelianov PhD (Biomechanical Engineering), Matthew O'Donnell PhD (Biomedical Engineering), Daniel Myers, Jr DVM, MPH, Thomas W Wakefield MD

Funding: National Institutes of Health

This project will use a new technique of elasticity quantification to age venous thrombi.

Thrombus Resolution is CXC Chemokine Dependent

Investigators: Peter Henke MD (PI), Thomas Wakefield MD

Funding: National Institutes of Health

The project evaluates factors responsible for thrombus resolution after DVT.

Inhibition of DVT Induced Inflammation and Thrombosis by rPSGL-Ig

Investigators: Thomas Wakefield, MD (PI), Daniel Myers, Jr, DVM, MPH, Shirley Wrobleski, BS, LVT, Frank Londy, RT (Radiology), Peter Henke, MD, Lazar J. Greenfield, MD

Funding: Genetics Institute/Wyeth

This project evaluates the use of a PSGL-1 receptor antagonist to limit inflammation and thrombosis during and after venous thrombosis produced by temporary venous balloon occlusion. It also assesses the ability of the same PSGL-1 receptor antagonist to augment spontaneous venous thrombolysis.

Inhibition of Deep Vein Thrombosis (DVT)- Induced Inflammation and Thrombosis by Melagatron

Investigators: Thomas Wakefield, MD (PI), Daniel Myers, Jr, DVM, MPH, Shirley Wrobleski, BS, LVT

Funding: AstraZeneca

This project will assess the effects of Melagatron in an IVC ligation model.

Supervised Calf Muscle Exercise in Patients with Chronic Venous Insufficiency and Wearing Compression Stockings

Investigators: Paul Zajkowski, BS, Thomas Wakefield MD, Mary Proctor MS, Thomas Draper (Preventive Cardiology)

Funding: BSN-Jobst

This project will determine the effect of a supervised exercise program on venous insufficiency.

Enhancing Intrinsic Regeneration to Tissue Engineer a Peripheral Nerve Graft

Investigators: William Kuzon (PI, Plastic Surgery), Thomas Wakefield MD

Funding: UM Center for Biomedical Engineering Research

The project will examine the role of inflammation and its inhibition in peripheral nerve graft biology.

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.

Deep Venous Thrombosis Resolution is CXC Chemokine-dependent

Investigators: Peter K. Henke, MD, Andrea Varga, BS, Pasu Sukheepod, MD, Thomas W. Wakefield, MD

Funding: National Institutes of Health, KO8

The purpose of this study is to define the role of CXC chemokines and neutrophils in DVT resolution, along with their effect on PMN lytic activity in vitro.

P-selectin and DVT mediated pathogenesis

Co-investigator: Thomas W. Wakefield, MD, Peter K. Henke, MD

This project will evaluate the role of P-selectin in the pathogenesis of venous thrombosis.

Role of endothelial damage in vein wall fibrotic response after DVT

Investigator: Peter K. Henke, MD

This study will evaluate the mechanisms of vein wall re-endothelialization after DVT and therapies to accelerate this response. Rodent models and in vitro analyses will be done.

Matrix metalloproteinases and vein wall damage after DVT

Investigators: Thomas W. Wakefield, MD, Peter K. Henke, MD, Gilbert R. Upchurch, Jr., MD

The goal of this project is to evaluate the role of the MMP-2 and -9 in vein wall remodeling after DVT in an animal model (with varying thrombotiic conditions), as well as in a human cohort in whom acute DVT has occurred.

uPA and MMP activation in DVT resolution

Investigator: Peter K. Henke, MD

This project will evaluate the reciprocal interaction of the MMPs and uPA in the vein wall response and how it affects thrombus resolution in rodent models. Modulation of the MMP response will also be done with lymphokines such as interferon-gamma.