Thoracic Cardiovascular Surgery
Research Opportunities
Click on the titles to take you to further details in each area.
LUNG TRANSPLANT ISCHEMIA-REPERFUSION INJURY
Although there has been considerable progress in lung transplant biology, post-transplant ischemia-reperfusion (IR) injury remains the major source of early mortality. Our lab is utilizing several animal models of IR injury to study mechanisms of this injury in terms of endothelial cell injury, the role of adenosine and nitric oxide and the role of resident lung leukocytes.
COMPENSATORY LUNG GROWTH
Pneumonectomy (removal of a lung) results in rapid, hyperplastic, compensatory growth of the remaining lung. The molecular mechanisms that regulate this regenerative growth are not well known. An understanding of these mechanisms and the role of angiogenesis and angiogenic growth factors in this growth could lead to therapies for lung injury, pulmonary hypertension, respiratory failure, transplantation for endstage lung disease, and even stimulation of regenerative growth in patients with minimal pulmonary tissues left after lung resection.
AORTIC ANEURYSM FORMATION
Aortic aneurysms comprise the 10th leading cause of death accounting for more than 16,000 deaths yearly. To date, there have been no medical therapies proven to prevent or treat aortic aneurysms. Thus, understanding molecular mechanisms for this disease are critical to developing novel treatment strategies. The majority of laboratories investigating aortic aneurysms have focused on leukocyte infiltration and MMP production, while little is known about the role of smooth muscle cells (SMCs). Early in the course of aneurysm formation, SMCs undergo proliferation; however, in maturing aneurysms, smooth muscle cells (SMCs) undergo apoptosis, thereby eliminating cells that are the primary source for the extracellular matrix. There is significant data to suggest SMCs are plastic and have the ability to undergo phenotypic switching in response to environmental cues. One of our goals is to identify SMC phenotype during aneurysm formation. Of major significance, studies in our lab are determining the role of IL-1β induced changes in SMC gene expression as well as direct assessment of the role of IL-1 signaling in SMC phenotypic switching in vivo during aneurysm formation using a variety of unique transgenic and knockout mice developed in the mentor's laboratory. Further experiments include the use of a conditional KLF4 KO mouse, a downstream effector of IL-1β developed by the mentor to determine the mechanisms by which IL-1β exerts its effects. With expanded knowledge of the regulators of SMC phenotype in aneurysm formation, these experiments may lead to novel therapies to alter SMC phenotype, cease degradation of the aortic wall, and remodel the aortic wall matrix.
SPINAL CORD INJURY
Many people suffer traumatic spinal cord injuries in the United States every year. Young victims of violent trauma are often left paralyzed because of our inability to limit spinal cord injury following the inciting traumatic event. In addition, many other people suffer spinal cord injury following surgery to correct certain abnormalities of the thoracic aorta. The spinal cord is very sensitive to even brief periods of decreased blood flow. When the thoracic aorta is clamped in order to repair thoracic aortic aneurysms, the spinal cord may suffer from a lack of blood flow. Following spinal cord trauma, blood flow to the injured area of the cord can also be significantly reduced. Lack of blood flow to the spinal cord can result in unrecoverable cord injury and degeneration. We have developed a reliable method of perfusing the spinal cord with cold protective solutions through the veins of the spinal cord, instead of through the arteries (which become blocked during spinal cord trauma or thoracic aortic surgery).