Research Summary

Traditional revascularization techniques including percutaneous transluminal coronary angioplasty (PTCA) and coronary artery bypass graft surgery (CABG) are the current clinical interventions for coronary artery occlusions.   In approximately 30-50% of the patients that undergo PTCA, restenosis is thought to occur primarily as a result of smooth muscle cell (SMC) proliferation and matrix formation.  After CABG approximately 50% of the saphenous veins grafts become occluded within 5-10 years, again, due to SMC proliferation and matrix formation.  Because of the clinical and economic issues raised by failure of revascularization interventions, inhibition of SMC growth is a major target of experimental studies and therapeutic design. Understanding the SMC response to injury is fundamental to the development of interventional strategies aimed at inhibiting SMC proliferation, but maintaining vascular function.

One line of my research focuses on the RNA binding protein hnRNP-K, which participates in this SMC growth response.  We are particularly interested in the trafficking function of hnRNP-K as well as its post-translational modifications and protein partners during SMC growth.  hnRNP-K interacts with proteins from specific signaling pathways and with a SMC-specific actin binding protein. I aim to learn how hnRNP-K functions to regulate SMC growth and how hnRNP-K is regulated in SMCs.  Toward this end, we have investigated the function of hnRNP-K in SMC using cardiovascular therapeutics alone and in combination with known inhibitors of signal transduction cascades to define cellular pathways that coordinate the SMC response. Our ultimate goal is to identify a novel mechanism of inhibiting this protein that will attenuate the SMC proliferative response.

In a second line of research and in collaboration with George Prendergast's group, we are defining the role of RhoB in SMC to mediate the PDGF response, potentially via an Akt-dependent mechanism. RhoB is targeted by farnesyl transferase inhibitors (FTIs), a class of anti-cancer therapeutics currently in clinical trials.  One goal of this work is to explore the ability of FTI to limit SMC growth in atherosclerosis in combination with statins.

Selected Publications

1. Laury-Kleintop, L.D., Gleason, M. and Tulenko, T.N. (1999). Expression of the Heterogeneous Nuclear Ribonucleoprotein Complex K Protein and the Prolyl-4-Hydroxylase subunit in Atherosclerotic Arterial Smooth Muscle Cells.  Biochem. Biophys. Res. Comm.  260:382-389.
2. Tulenko, TN, Sumner, AE, Chen, M, Mason, RP, Laury-Kleintop, L.D., and Ferdinand, F. (2001). Novel issues in Atherogenesis: The smooth muscle cell membrane. Am Heart J. 141:S1-11.
3. Lan L, Hayes CS, Laury-Kleintop L, and Gilmour SK. (2005). Suprabasal induction of ornithine decarboxylase in adult mouse skin is sufficient to activate keratinocytes. J. Invest. Dermatol. 124: 602-611.
4. Huang, M., Prendergast, G.C., and Laury-Kleintop, L.D. RhoB deletion abolishes PDGF-regulated Akt signaling during smooth muscle cell growth. In preparation.