Project 1: Regulation of Endothelial Lipid Metabolism in Peripheral Arterial Disease (PAD)
My laboratory focuses on molecular, biochemical, and hemodynamic processes that impact the progression of different forms of PAD in the setting of diabetes. My lab was the first to demonstrate that phospholipogenesis is significantly altered in the peripheral arterial tissue of patients with diabetes. We were also the first to make a rodent model for hindlimb ischemia and amputation, to explore potential therapies that can improve perfusion and healing in the setting of chronic ischemia and diabetes. Using this model, we demonstrated that administration of thiol medications can improve tissue perfusion and healing in the setting of diabetes (see N-Acetylcysteine accelerates amputation stump healing in the setting of diabetes). In another study, we also shed light on some of the molecular processes that lead to atherosclerotic plaque progression in the setting of diabetes (see Diabetes aversely affects phospholipid profiles in human carotid artery endarterectomy plaques). Our ongoing projects now include investigator-led clinical trials, as well as bench-top studies evaluating the molecular and biochemical consequences of altered lipogenesis in the peripheral arterial tissue. We utilize murine genetic models, high-fidelity biochemical assays, and state-of-the-art molecular techniques to help identify potential drug targets that can ultimately impact the clinical progression of PAD.
Project 2: PET Detection of CCR2 in Human Atherosclerosis
Through a multidisciplinary collaboration with the Washington University School of Medicine Mallinckrodt Institute of Radiology, we are translating recent findings in molecular signaling of atherosclerosis. We are performing first-in-human clinical trials to evaluate the utility of a novel PET radiotracer in detecting vulnerable atherosclerotic plaques in individuals with clinically significant carotid artery stenosis and PAD. Since atherosclerosis in these arterial beds is a major source of morbidity and mortality, we believe that developing this novel diagnostic technique will help further our ability to better detect which patients would benefit most from surgical intervention. Additionally, since the radiotracer targets an important macrophage mediated inflammation pathway, our studies will help inform future immune-modulating studies that aim to reduce the risk of atheroprogression, stroke, and PAD.
Project 3: CCR Targeted Molecular Imaging and Treatment of Abdominal Aortic Aneurysms
Through another multidisciplinary collaboration with the Washington University School of Medicine Mallinckrodt Institute of Radiology we are evaluating a novel theranostic strategy to both diagnosing and treating abdominal aortic aneurysms that are prone to rupture. The goal of this project is to assess whether CCR2+ inflammatory processes associated with AAA development and exploit these processes as therapeutic targets in rodent AAA models, while exploring targeted CCR2 PET imaging in patients with AAA.