Kent Vascular Research Laboratory
K. Craig Kent, MD
Dr. Kent’s NIH-funded research programs focus on the investigation of the mechanisms of failure for angioplasty and bypass grafts with the goal of developing new methods for treatment. He has a longstanding history as an investigator on industry-sponsored clinical trials. Dr. Kent has been named one of the Best Doctors® in America and has been recognized for his academic excellence in clinical as well as basic science research.
Major Research Interests
Dr. Kent has built a multi-disciplinary vascular research team conducting investigations that are basic, translational and clinical. His primary interest of basic research is to understand the transforming growth factor beta (TGF-beta)-mediated molecular mechanisms of restenosis with the goal of identifying new therapeutic targets. Dr. Kent and his long-term research partner, Dr. Bo Liu, have demonstrated the importance of the interaction of TGF-beta and protein kinase C-delta in intimal hyperplasia following vascular injury.
Specifically, Dr. Kent’s research is focused on the role of TGF-beta and its primary signaling protein SMAD3 in intimal hyperplasia and constrictive vessel remodeling, both important contributors to restenotic vascular occlusion. There is strong evidence supporting a critical role for TGF-beta in the development of restenosis following vascular intervention, but the exact underlying mechanisms are not well understood.
TGF-beta is traditionally known to be an in vitro inhibitor of smooth muscle cell proliferation and migration, seemingly contradictory to its stimulatory effects on neointimal thickening. However, Dr. Kent’s laboratory has discovered that in the presence of elevated SMAD3, TGF-beta stimulates rather than inhibits cell proliferation. Thus, a novel mechanism has been revealed in a rat carotid angioplasty model, in which TGF-beta in the background of increased SMAD3 stimulates smooth muscle cell proliferation and enhances intimal hyperplasia. Equally interestingly, TGF-beta activation has often been associated with constrictive remodeling of the vessel wall, but Dr. Kent’s group has demonstrated that medial gene transfer of SMAD3 promotes vessel expansion in the angioplastied artery. In addition, we have also found a new role of TGF-beta and SMAD3 in the post-injury recruitment of bone marrow-derived progenitor cells that promotes neointimal growth. Multiple pathways activated by the TGF-beta/SMAD3 axis that contribute to intimal hyperplasia or arterial remodeling are being uncovered and leading to translational research in Dr. Kent’s laboratory.
Another important facet of Dr. Kent’s research is the development of new materials and approaches for drug delivery to inhibit intimal hyperplasia. Although drug-eluting stents are currently used to treat restenotic disorders, clinically applicable perivascular drug delivery systems, which are expected to prevent systemic or stent-induced side effects, have not been established. In collaboration with Dr. Sarah Gong and Dr. William Murphy, both professors of biomedical engineering, Dr. Kent’s laboratory is testing periadventitial drug delivery to suppress intimal hyperplasia using nanoparticles and biocompatible polymers. As an integral part of this translational endeavor, we are searching for specific TGF-beta/Smad3-inhibiting agents by collaborating with Dr. Michael Hoffmann, the Romnes Professor of Oncology and Medical Genetics leading the Small Molecule Screening & Synthesis Facility.
Ultimately, the goal of our basic and translational research is to identify efficacious interventional agents to treat restenosis by applying multidisciplinary approaches on integral intracellular signaling and in vitro/in vivo models.
Additional research interests
- Stem Cells – the role and regulation of bone marrow-derived progenitor cells in vascular diseases; in vitro differentiation of stem cells to vascular smooth muscle cells.
- Drug delivery – development of tissue-specific drug delivery for vascular diseases
- Tissue engineering – development of arterial grafts
- Outcome research – to compare various vascular managements for their clinical efficacy and cost-effectiveness