Nicholas P. Ziats, Ph.D. Associate Professor of Pathology, Biomedical Engineering, and Anatomy Mailing Address: 2103 Cornell Rd. WRB 5143 Cleveland, OH 44106-7288 phone: (216) 368-5176 fax: (216) 368-0494 email: Nicholas.Ziats@Case.edu

Biography
Dr. Nicholas P. Ziats received his Ph.D. in Experimental Pathology from the Department of Pathology at Case Western Reserve University, Cleveland, Ohio in 1987. He became an Assistant Professor of Pathology in 1991 and adjunct appointments in Biomedical Engineering in 1995 and in Anatomy in 2003. Dr. Ziats' major research interest is in vascular biology, angiogenesis and tissue engineering. His other major interest is in medical education.

Research
The overall goal of our research is the investigation into disorders affecting blood vessels. We are currently studying the role of endothelial cells in vascular graft failure and in angiogenesis associated with tumors. We are particularly interested in mechanisms of incomplete endothelialization of these vascular grafts (which is unique to humans but not animals), as well as methods to improve endothelialization of grafts. Our studies suggest that components of the extracellular matrix (collagens, proteoglycans, coagulation proteins) may directly influence the growth, migration and functional expression of proteins of endothelial cells on materials. We have been particularly interested in the role of High Molecular Weight Kininogens (HMWKs) as modulating endothelial function in vitro and in vivo. We are using Confocal Laser Scanning Microscopy to identify the expression of cell adhesion/cytoskeletal proteins as well cytoskeletal organizations of endothelial cells cultured under various conditions. In addition, we are interested in determining whether human endothelial cells adhere to and grow on reference or candidate synthetic materials and/or stent materials to be used as treatment for vascular disease. In another aspect, related to clinical trials and evaluations, we are addressing the role of endothelial cells in angiogenesis and the effects of antiangiogenic agents as therapeutic agents. The studies involve microscopic evaluation of blood vessels (microvessel density) in human tissue obtained from patients undergoing therapeutic treatment with novel antiangiogenic drugs. In addition, other ongoing research is addressing the role of HMWKs as antiangiogenic agents using in vitro and in vivo assays. Overall, these combined studies are aimed at a better understanding of endothelial cells and their role in vascular disease.

Publications
Voskerician G, Anderson JM, Ziats NP (2000). High molecular weight kininogen inhibition of endothelial function on biomaterials. J Biomed Mater Res 51, 1-9.

Kader K, Akella R, Ziats NP, Lakey L, Harasaki H, Ranieri JP, Bellamkonda RV (2000). eNOS overexpressing endothelial cells inhibit platelet aggregation and smooth muscle proliferation in vitro. Tissue Engineer 6, 241-251.

Kader K, Moore LR, Saul JM, Zborowski M, Ziats NP, Bellamkonda RV (2001). Isolation and purification of canine microvascular endothelial cells. Microvasc Res 61, 220-226.

Zhang J-C., Donate F, Ziats N.P, Mazar AP, Pang Y-P, Lin JJ-C, McCrae KR (2002). The antiangiogenic activity of cleaved high molecular weight kininogen is mediated through binding to endothelial cell tropomyosin. Proc Natl Acad Sci. 99:12224-1229.

Wood LS, Ziats NP (2002). Vascular Targeting: case study: 55-year-old man with stage IV anaplastic thyroid cancer. Horizons in Cancer Therapeutics: From Bench to Bedside, 3:24-25.

Brodbeck WG, Voskerician G, Ziats NP, Nakayama Y, Matsuda T, Anderson JM (2003). In vivo leukocyte cytokine mRNA responses to biomaterials is dependent on surface chemistry. J. Biomed. Mater. Res. 64A:320-329, 2003.

Dowlati A, Robertson K, Radivoyevitch T, Waas J, Ziats NP, Hartman P, Overmoyer B, Abdul-Karim FW, Wasman JK, Jesberger J, Lewin J, Cooney M, McCrae K, Ivy P, Remick SC (2005). Novel Phase I Dose De-escalation Design Trial to Determine the Biological Modulatory Dose of the Anti-Angiogenic Agent SU5416. Clin Cancer Res, 11:7938-7944.