The investigative activities of the faculty in this cardiovascular and pulmonary research training program are organized around 5 thematic areas (A, B, C, D, E) as they relate to heart, vascular and lung diseases. These theme areas shown below, provide general topics for joint lab meeting to review data, collaborative research projects between labs, and interdisciplinary graduate training efforts. The thematic areas displayed in the diagram below also reflect general areas of research funding and expertise of many (but not all) the training faculty.
Examples of Generalized Collaborative Projects Available to Graduate Students:
Thematic Area A: Angiogenesis and Vascular Development
Collaborators: Drs. Wysolmerski, Liu, and Mustafa
Students choosing this project will use an array of cellular and molecular techniques to investigate the signaling pathways involved in angiogenesis and the growth and differentiation of new blood vessels. Ongoing studies look at myosin IIA and IIB in cell contractility, caveolin in the spatial organization of signaling events required for lamellipodium protrusion, and the expression of VEGF and PI-3 kinase in endothelial cells affecting the induction of angiogenesis by tumors.
Thematic Area B: Inflammation and Oxidative Stress Endothelial/Epithelial Injury
Collaborators: Drs. Boegehold, Frisbee, Mustafa, Wysolmerski, Piedimonte, Dey and Nurkiewicz
Students choosing this project will use a combination of cellular/molecular, pharmacological, and imaging techniques to investigate the mechanisms by which the inflammation and oxidative stress influence endothelial/epithelial injury. For example, how high salt intake leads to generation of reactive oxygen species & ultimately blood pressure; impairment of endothelium in obesity and diabetes can lead to impairment of bioavailability of nitric oxide; in chronic inflammation of the gut, how does Na-glucose co-transport/Na-amino acid transport is affected.
Thematic Area C: Epithelial/Endothelial Control of Vascular Tone and Permeability
Collaborators: Drs. He, Boegehold, Minnear, Rajendran, Wysolmerski and Sundaram
Students choosing this project will use a combination of in vivo microscopy, cellular biochemical assays, viral vector methodologies, permeability measurements across cell monolayers, single microvessels, and small intestine, and image analyses to investigate the pathological mechanisms by which inflammatory agents as well as permeability-enhancing agents can influence the regulation of blood flow and vascular endothelial/epithelial permeability via interactions of the actin-myosin cytoskeleton and the adherens junctions proteins.
Thematic Area D: Myocardial Function and Coronary Blood Flow
Collaborators: Drs. Finkel, Hollander, Yu and Mustafa
Students choosing this project will use cellular/molecular techniques, viral vector methodologies, transgenic rodent models, and functional assessment of the microcirculation and myocardium to investigate the contribution of inflammation and to depression of myocardial function linked to ischemia-reperfusion. Students will also be able to investigate using cellular and molecular techniques (including transgenic rodent models), electrophysiological measurements, isolated microvessels, and pharmacological approaches to investigate the mechanisms underlying the regulation of coronary perfusion and myocardial contractility. For example, what is the role of adenosine receptors (four subtypes) in the regulation of coronary flow (we will use the all four adenosine receptor knockout mice for these experiments); how cardiac function is affected by depression; how antioxidant defenses (mitochondrial phospholipid hydroperoxide glutathione peroxidase) protect the cardiac cell damage from reactive oxygen species, how ANP plays a role in neurogenic inflammation in the lung, how respiratory infections at an early age lead to the development of asthma.
Thematic Area E: Airway Responsiveness and Remodeling
Collaborators: Drs. Castranova, Dey, Mustafa, Piedimonte and Nurkiewicz
Students choosing this project will use various molecular, cellular, and biochemical techniques, often in combination with direct in vivo assessment of microvascular behavior, to investigate local and systemic inflammatory processes that disrupt pulmonary and vascular function after exposure to airborne particulates. Also, students will be able to investigate the contributions of oxidant stress, inflammation, and airway nerve activity to childhood or occupational asthma. For example, what is the role of A2A adenosine receptor in airway reactivity and inflammation and its relationship to oxidative stress; what are the mechanisms of inhaled welding fumes (main constituent is manganese) on airway reactivity and inflammation.