Dr. Li is an Associate Professor at Department of Pharmaceutical Sciences and a member of the Center for Pharmacogenetics, University of Pittsburgh School of Pharmacy. He received his M.D. and Ph.D. from the Fourth Military Medical University, Xi’an, China, and pursued his postdoctoral training with Dr. Leaf Huang. He became a faculty at the University of Pittsburgh School of Pharmacy in 2000. Dr. Li has broad knowledge in medicine, biology, and drug and gene delivery and is the author or co-author of over 70 peer-reviewed articles and 25 review articles or book chapters. He is an Associate Editor for Journal of Gene Medicine and frequently serves on NIH and AHA study sections. Research in Dr. Li’s lab has been supported by NIH, DOD, and American Heart Association (AHA).

Research Interest:

Dr. Li’s research is mainly focused on the development of lipid- and polymer-based nanodelivery systems for targeted delivery of various types of therapeutics including nucleic acids (genes, siRNA, and peptide nucleic acids), proteins, and small molecules (e.g., anticancer agents and antioxidants). Emphases are placed on the discovery of small molecule-based targeting ligands and development of strategies to overcome cellular and in vivo barriers. Another research project in Dr. Li’s group is farnesoid X receptor (FXR)-mediated gene regulation in vascular cells and hepatic stellate cells.

Drug & Gene Delivery:
Dr. Li’s group has developed a neutral lipid vector that is highly efficient in selective delivery of small-sized nucleic acids (antisense oligos and siRNA). Studies are underway to further improve this system and to examine its therapeutic effect in animal models of pulmonary hypertension, liver cirrhosis, and cancers.

Recent work in Dr. Li’s lab has also led to development of a new series of polymers that show improved transfection and significantly decreased toxicity compared to PEI-based systems. The simplicity and versatility of the synthesis scheme allows generation of a library of compounds for detailed structure-function studies. In addition, functional domains (PEG, ligands, fusogenic peptides) can be readily incorporated into the polymers to provide new functionalities to improve gene delivery efficiency. These polymers are currently under evaluation for delivery of urokinase plasminogen activator (uPA) transgene or tumor suppressor genes for the treatment of acute lung injury or cancers.

In addition to nucleic acid therapeutics, Dr. Li’s group is also interested in targeted delivery of small molecule drugs such as anticancer cancer agents. As a Core of Smart Drug Delivery of the University of Pittsburgh Center for Medical Counter Measures Against Radiation (CMCR) Program, his lab is involved in the development of novel formulations for delivery of novel radiation mitigators.

Gene Regulation:
In addition to studies on drug and gene delivery, Dr. Li’s group is also involved in gene regulation. Recent studies from his group have revealed several novel roles of FXR in regulation of vasoactive mediators and anti-fibrotic genes in vascular endothelial/smooth muscle cells and hepatic stellate cells. The long-term goals of these studies are to identify novel therapeutic targets for the treatment of vascular diseases and liver cirrhosis.

Publications:

Zhou, W., Yuan, X., Wilson, A., Yang, L., Mokotoff, M., Pitt, B., and Li, S. Efficient intracellular delivery of oligonucleotides formulated in folate receptor-targeted lipid vesicles. Bioconjugate Chemistry 13: 1220-1225, 2002.

Banerjee, R., Tyagi, P., *Li, S., and *Huang, L. Anisamide-targeted stealth liposomes: a potent carrier for targeting doxorubicin to prostate cancer cells. International Journal of Cancer 112: 693-700, 2004 (*co-correspondence author).

Wilson, A., Zhou, W., Champion, H., Alber, S., Tang Z.-L., Kennel, S., Watkins, S., Huang, L., Pitt, B., and Li, S. Targeted delivery of oligodeoxynucleotides to mouse lung endothelial cells in vitro and in vivo. Molecular Therapy 12: 510-518, 2005.

He, F., Li, J., Mu, Y., Kuruba, R., Ma, Z., Wilson, A., Alber, S., Jiang, Y., Stevens, T., Watkins, S., Pitt, P., Xie, W., and Li, S. Downregulation of endothelin-1 by farnesoid X receptor in vascular endothelial cells. Circulation Research 98: 192-199, 2006.

Straub, A.C., Clark, K.A., Ross, M.A., Chandra, A.G., Li, S., Gao, X., Pagano, P.J., Stolz, D.B., and Barchowsky, A. Arsenic-stimulated sinusoidal capillarization in mice requires NADPH oxidase generated superoxide. Journal of Clinical Investigation 118: 3980-3989, 2008.

Gao, X., Kuruba, R., Achary, D.K., Day, B.W., Liu, D., and Li, S. Polyhydroxylalkyleneamines: a class of hydrophilic polymer-based gene transfer agents. Journal of Controlled Release 137: 38-45, 2009.

Li, J., Wilson, A., Gao, X., Kuruba, R., Liu, Y.H., Poloyac, S., Pitt, B., Xie, W., and Li, S. Coordinated regulation of dimethylarginine dimethylaminohydrolase-1 and cationic amino acid transporter-1 by farnesoid X receptor in mouse liver and kidney and its implication in the control of blood levels of asymmetric dimethylarginine. Journal of Pharmacology and experimental Therapeutics 331: 234-243, 2009.

Li, J., Zhang, Y., Kuruba, R., Gao, X., Gandhi, C.R., Xie, W., and Li, S. Roles of miR-29a in the antifibrotic effect of FXR in hepatic stellate cells. Molecular Pharmacology 80: 191-200, 2011.

Kim, H., Bernard, M.E., Epperly, M.W., Shen, H., Amoscato, A., Dixon, T.M., Doemling, A.S., Li, S., Gao, X., Wipf, P., Wang, H., Zhang, X., Kagan, V.E., and Greenberger, J.S. Amelioration of Radiation Esophagitis by Orally Administered p53/Mdm2/Mdm4 Inhibitor (BEB55) or GS-Nitroxide. In Vivo 25: 841-848, 2011