Shi Pan, Ph.D.

Shi Pan, Ph.D. Instructor Shi_Pan@urmc.rochester.edu Primary Appointment: Department of Medicine in the Aab Cardiovascular Research Institute University of Rochester School of Medicine and Dentistry 601 Elmwood Ave, Box 679 MRBX - Rm. 2.11001 Rochester, New York 14642 Phone: (585) 273-1533 Fax: (585) 276-1914

Dr. Pan received her Ph.D. form the University of Tokyo, Japan in 1998 in Molecular and Cellular Biology. Her postdoctoral training was done at the University of Tokyo where she continued her research on the regulation of cytokine gene expression and at the University of Pittsburgh where she worked on VEGF mediated angiogenesis. She was recruited to the University of Rochester as an Instructor in Medicine in 2002.

Research Overview

Reactive oxygen species (ROS) are generated in all aerobic organisms as the result of normal cellular metabolism. A balance of generating and neutralizing processes establishes the redox homeostasis, which is important for normal cell function. Alteration of the redox homeostasis by the increased generation of ROS is implicated in the pathophysiology of a variety of vascular diseases, including coronary artery disease, arrhythmias, congestive heart failure, cardiomyopathy, atherosclerosis, hypertension, ischemia-reperfusion injury and diabetes.

The intracellular milieu is usually a reduced environment resulting from a high concentration of glutathione. In cells experiencing oxidative stress, a continual supply of reducing equivalents in the form of NADPH is required, which is provided by pentose phosphate pathway. Glutathione protects cells against ROS through a variety of mechanisms by using NADPH as a reducing power.

When exposed to ROS, reactive-thiol-containing proteins undergo certain post-translational modifications. One of them is S-glutathionylation, the formation of glutathione-mixed disulfide bond, which protects protein from loss of function caused by irreversible oxidation. Glutathionylated proteins contain cytoskeletal proteins, signaling molecules including phosphatases and kinases, and transcription factors, which indicates that glutathionylation is an important mechanism that links the changes in the intracellular redox potential to the regulation of protein function.

The aim of Dr. Pan’s research is to understand the redox regulation of vascular function. It has been found that laminar shear stress exerts atheroprotective function by regulating the redox potential and gene expression of endothelial cells. Understanding the redox modification of protein function will be a critical step in determining the molecular mechanism of ROS-induced endothelial dysfunction and, in addition, may provide potential targets to the treatment of cardiovascular diseases.

Recent Publications

1. Hideyuki, Y., Pan S., Lee, R.T., and Berk, B.C. (2005) Fluid shear stress is anti-inflammatory by decreasing thioredoxin interacting protein (TXNIP) in endothelial cells. J Clin Invest In press.
2. Pan, S., An, P., Zhang, R., He, X., Yin, G., and Min, W. (2002) Etk/Bmx as a TNFR2-specific kinase: role in endothelial cell migration and angiogenesis. Mol Cel Biol 22 (21): 7512-7523.
3. Guo, P., Xu, L., Pan, S., Brekken, R., Yang, S.-T., G. Brian Whitaker, Nagane, M., Philip Thorpe, Jan Rosenbaum, Su Huang, H.-J., Cavenee, W. K. and Cheng, S.-Y. (2001) Vascular endothelial growth factor isoforms display distinct activities in promoting angiogenesis at different anatomic sites. Cancer Res 61 (23): 8569-77.
4. Pan, S., Tsuruta, L.,Imamura, R., Masuda, E.S., Arai, N., Arai, K. and Miyatake, S. (2000) NFATz : a novel rel similarity domain containing protein. Biochem Biophys Res Commun 272(3): 765-76.