Dr. McGregor's Xenotransplantation and Gene Therapy Laboratory at Mayo Clinic has several ongoing research focus areas:
- Neoantigens. This area of Dr. McGregor's lab research focuses on investigating the identity of neoantigens in transplant.
- Vascular rejection. This research area focuses on developing new genetics to mitigate vascular rejection.
- Antibody-mediated cardiac rejection. Experimental cardiac transplant models are used to elucidate the effects of ischemic injury and vascular antibody reactivity on cardiac gene expression, function and rejection. Genome-wide expression studies are used to characterize changes in gene expression associated with ischemia-reperfusion injury, as occurs during clinical cardiac transplantation, and with chronic vascular antibody deposition. These studies are used to define markers for better diagnosis of antibody-mediated rejection and to gain insight into new therapeutic pharmaceutical or gene therapy treatments that minimize the effects of vascular antibody and enhance resistance to antibody-mediated cardiac rejection.
- Antibody-mediated degeneration of biological heart valves. Bioprosthetic heart valves are commonly produced from glutaraldehyde-fixed porcine aortic valves or sewn from fixed bovine pericardium. Such valves generally don't require anticoagulation, have a low level of thrombogenicity, and are used principally in older patients as a durable therapy for heart valve disease. Over time and in younger patients, degeneration of BHV occurs, resulting in mechanical failure, calcification and stenosis requiring further repair surgery. This degenerative process is due, in part, to immunological responses to the device. All patients produce a universal human preformed antibody, which binds to a dominant carbohydrate antigen (alpha-Gal) present in animal tissues. Antibody to alpha-Gal is sufficient to accelerate calcification of glutaraldehyde-fixed animal tissues in experimental models. We use normal pig tissue and tissues from genetically modified pigs, which do not produce the alpha-Gal antigen, to determine the role of anti-Gal antibody in BHV degradation and elucidate the mechanism of antibody-mediated process.