William Thiel, PhD, Research Assistant Professor in Hematology, Oncology and Blood and Marrow Transplantation, has been awarded a five-year, $1.9 million grant from the National Heart, Lung, and Blood Institute. This R01 will fund Dr. Thiel’s murine model research into the cell-specific sequence of events leading to the renarrowing of blood vessels after revascularization procedures.
The primary mechanism responsible for many acute vascular disorders is pathological vascular smooth muscle cell (VSMC) activation. While drug-eluting stents containing cell growth inhibitors are effective in preventing reblockage of vessels, they also impair re-endothelialization of the vessel wall. To prevent pathological VSMC growth but not re-endothelialization, identification of the cell-surface proteins that might be targeted by agents able to distinguish between VSMCs and endothelial cells is crucial.
Dr. Thiel and his team will focus on defining the cell-surface proteins and mechanism of action by which VSMC-targeting aptamers modulate VSMC but not endothelial cell processes through the application of CRISPR-Cas9 technology. They will also determine the impact of these cell- and process-specific ligands on neointimal formation and re-endotheliazation after acute vascular injury.
Dr. Thiel has also received a two-year, $200,000 Innovative Project Award (IPA) from the American Heart Association to further explore VSMC aptamer generation specific for cardiomyocytes using SELEX, or systematic evolution of ligands by exponential enrichment. This process will be used to generate cardiac-specific aptamer ligands, with a goal of providing cardiovascular researchers new avenues for developing mechanism-based therapeutics. As it is designed to do, the IPA will allow Dr. Thiel and his collaborator, Dr. Long-Sheng Song, support in pursuit of critical discoveries accelerating cardiovascular research in previously unexplored areas.