Dr. Li is a Professor at the Department of Pharmaceutical Sciences, and Director of the Center for Pharmacogenetics at the 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, immunology, and drug and gene delivery and is the author or co-author of over 175 peer-reviewed articles and 34 review articles or book chapters. Dr. Li serves on the editorial boards of several journals. He also frequently serves on the review panels of NIH, DOD, VA, and other funding agencies.
Research in Dr. Li’s lab has been continuously supported by grants from various funding agencies including NIH, DOD, and American Heart Association (AHA).
Dr. Li has established a strong research program centered at the interface of biology/immunology and biotechnology. His lab has developed several novel delivery systems that are aimed to solve major issues in his fields through improved understanding of the fundamental aspects of drug formulations and comprehensive structure-activity relationship (SAR) study. His group proposed the concept of “new amphiphilic surfactants with interfacial drug-interactive motif”, which has helped to solve the problem of formulating many “hard-to-formulate” drugs (Molecular Pharmaceutics, 2013; Biomaterials, 2015). Another breakthrough from Dr. Li’s group is the development of ultrasmall nanocarriers for improved cancer treatment (Theranostics, 2020; Biomaterials, 2021, Materials Today, 2023). Dr. Li’s group has discovered that covalent coupling of nucleosides-based drugs (such as gemcitabine, azacitidine, cytarabine, decitabine, and others) into an amphiphilic polymeric carrier led to a drastic reduction in sizes from ~150 to ~15 nm. This system is highly effective in codelivery of various front-line water-soluble and water-insoluble drugs. Due to its ultrasmall size, this technology holds promise in overcoming the challenge of ineffective tumor accumulation and penetration seen in cancer patients. More recently, his group has developed another new delivery system that is highly efficient in tumor accumulation through targeting CD44 on tumor endothelial cells (ECs) (Nature Nanotechnology, 2023). This system is suitable for delivery of small molecules or nucleic acids alone or codelivery of both types of therapeutics.
In addition to the development of improved delivery systems, Dr. Li’s group has sought to uncover new mechanisms involved in resistance to cancer chemotherapy and/or immunotherapy. His lab has recently identified glutamate metabotropic receptor 4 (GRM4) as a novel negative regulator in antitumor immunity in multiple tumor models (Science Advances, 2021). More recently, Dr. Li’s group has identified Xkr8 as a novel gene that is critically involved in chemotherapy-induced immune suppression and cancer relapse, suggesting a new combination therapy via targeting Xkr8 (Nature Nanotechnology, 2023). Dr. Li’s group is also interested in developing new therapies for noncancerous diseases including cardiovascular diseases and liver diseases through developing improved delivery systems and identification of new therapeutic targets.
Chen, Y., Chen, C.Y., Huang, H., Luo, Z., Mu, Y., Li, S. and Li, S. Knocking down of Xkr8 enhances chemotherapy efficacy through modulating tumor immune microenvironment. Journal of Controlled Release 2024; 370: 479-489. (PMID: 38685385)
Luo, Z., Wan, Z., Ren, P., Zhang, B., Huang, Y., West, R., Huang, H., Chen, Y., Nolin, T., Xie, W., Wang, J., *Li, S., and *Sun, J. In situ formation of fibronectin-enriched protein corona on epigenetic nanocarrier for enhanced synthetic lethal therapy. Advanced Science 2024; 11: e2307940. (PMID: 38482976).
Wang, Y., Pattarayan, D., Huang, H., Zhao, Y., Li, S., Wang, Y., Zhang, M., Li, S., and Yang, D. Systematic investigation of chemo-immunotherapy synergism to shift anti-PD-1 resistance in cancer. Nature Communications 2024; 15: 3178. (PMID: 38609378).
Luo, Z., Huang, Y., Batra, N., Chen, Y., Huang, H., Wang, Y., Zhang, Z., Li, S., Chen, C., Wang, Z., Sun, J., Wang, Q.J., Yang, D., Lu, B., Conway, J., Yu, A., and Li, S. Inhibition of iRhom1 by CD44-targeting nanocarrier for improved cancer immunochemotherapy. Nature Communications 2024; 15: 255. (PMID: 38177179).
Wan, Z., Huang, H., West, R.E., Zhang, M., Zhang, B., Cai, X., Zhang, Z., Luo, Z., Chen, Y., Zhang, Y., Xie, W., Yang, D., Nolin, T.D., Wang, J., Li, S*, and Sun, J*. Overcoming pancreatic cancer immune resistance by codelivery of CCR2 antagonist using a STING-activating gemcitabine-based nanocarrier. Materials Today 2023; 62: 33-50.
Chen, Y., Huang, Y., Li, Q., Luo, Z., Zhang, Z., Huang, H., Sun, J., Zhang, L., Sun, R., Bain, D.J., Conway, J.F., Lu, B., and Li, S. Targeting Xkr8 via nanoparticles-mediated in situ codelivery of siRNA and chemotherapy drugs for cancer immunochemotherapy. Nature Nanotechnology 2023; 18: 193-204. (PMID: 36424448).
Kumar, S., Das, S., Sun, J., Huang, Y., Singh, S.K., Srivastava, P., Sondarva, G., Nair, R.S., Viswakarma, N., Hoskins, K., Danciu, O., Rana, B., Li, S., and Rana, A. Mixed lineage kinase 3 and CD70 cooperation sensitize trastuzumab-resistant HER2 + breast cancer by ceramide-loaded nanoparticles. PNAS 2022; 119: e2205454119. (PMID: 36095190).
Wan, Z., Sun, R., Liu, Y.W., Li, S., Sun, J., Li, J., Zhu, J., Moharil, P., Zhang, B., Ren, P., Ren, G., Ma, X., Dai, S., Yang, D., Lu, B., and Li, S. Targeting metabotropic glutamate receptor 4 for cancer immunotherapy. Science Advances 2021; 7: eabj4226. (PMID: 34890233)
Huang, H., Huang, Y., Chena, Y., Luo, Z., Zhang, Z., Sun, R., Wan, Z., Sun, J., Lu, B., Zhang, L., Hu, J., and Li, S. A novel immunochemotherapy based on targeting of cyclooxygenase and induction of immunogenic cell death. Biomaterials 2021; 270: 120708. (PMID: 33578254)
Sun, J., Wan, Z., Xu, J., Luo, Z., Ren, P., Zhang, B., Diao, D., Huang, Y., and Li, S. Tumor size-dependent abscopal effect of polydopamine-coated all-in-one nanoparticles for immunochemo-photothermal therapy of early and late-stage metastatic cancer. Biomaterials 2021; 269: 120629. (PMID: 33387938)
Sun, J., Chen, Y., Xu, J., Song, X., Wan, Z., Du, Y., Ma, W., Li, X., Zhang, L., and Li, S. High loading of hydrophobic and hydrophilic agents via small immunostimulatory carrier for enhanced tumor penetration and combinational therapy. Theranostics 2020; 10: 1136-1150.
Xu, J., Wang, B., and Li, S. Gene and Cell Therapy. In: “Remington: The Science & Practice of Pharmacy”, A. Adejare (Ed.), Academic Press, 23rd Edition, pp463-488, 2020.
Xu, J., Sun, J., Ho, P.Y., Luo, Z., Ma, W., Zhao, W., Rathod, S., Fernandez, C., Venkataramanan, R., Xie, W., Ai-Ming Yu, A.M., and Li, S. Creatine based polymer for codelivery of bioengineered microRNA and chemodrugs against breast cancer lung metastasis. Biomaterials 2019; 210: 25-40. (PMID: 31054369).
Xu, J., Zhao, W., Sun, J., Huang, Y., Wang P., Wenkataramanan, R., Yang, D., Ma, X., Rana, A., and Li, S. Novel glucosylceramide synthase inhibitor based prodrug micelles for delivery of anticancer agents. Journal of Controlled Release 2018; 288: 212-226. (PMID: 30223045).
Chen, Y., Xia, R., Huang, Y., Zhao, W., Li, J., Zhang, X., Wang, P., Venkataramanan, R., Fan, J., Xie, W., Ma, X., Lu, B., and Li. S. An immunostimulatory nanocarrier that improves cancer immunochemotherapy. Nature Communication 7: 13443, 2016. (PMID: 27819653).
Zhang, P., Li, J., Ghazwani, M., Zhao, W., Huang, Y., Zhang, X., Venkataramanan, R., and Li, S. Effective co-delivery of doxorubicin and dasatinib using a PEG-Fmoc nanocarrier for combination cancer chemotherapy. Biomaterials 67: 104-114, 2015. (PMID: 26210177).
Lu, J., Liu, C., Wang, P., Ghazwani, M., Xu, J., Huang, Y., Ma, X., Zhang, P., and Li, S. The self-assembling camptothecin-tocopherol prodrug: an effective approach for formulating camptothecin. Biomaterials 62: 176-187, 2015.
Zhang, X., Huang, Y., Zhao, W., Liu, H., Marquez, R., Lu, J., Zhang, P., Zhang, Y., Li, J., Gao, X., Venkataramanan, R., Xu, L., and Li, S. Targeted delivery of anticancer agents via a dual function nanocarrier with an interfacial drug-interactive motif. Biomacromolecules 15: 4326-4335, 2014 (PMID: 25325795).
Lu, J., Zhao, W., Liu, H., Marquez, R., Huang, Y., Zhang, Y., Li, J., Xie, W., Venkataramanan, R., Xu, L., and Li, S. An improved D-α-tocopherol-based nanocarrier for targeted delivery of doxorubicin with reversal of multidrug resistance. Journal of Controlled Release 196: 272-286, 2014. (PMID: 25456831)
Zhang, P., Huang, Y., Liu, H., Marquez, R., Lu, J., Zhao, W., Zhang, X., Gao, X., Li, J., Venkataramanan, R., Xu, L., Li, S. A PEG-Fmoc conjugate as a nanocarrier for paclitaxel. Biomaterials 35: 7146-7156, 2014. (PMID: 24856103)
Gao, X., Huang, Y., Makhov, A.M., Epperly, M., Lu, J., Grab, S., Zhang, P., Rohan, L., Xie, X.Q., Wipf, P., Greenberger, J., and Li, S. Nano-assembly of surfactants with interfacial drug-interactive motifs as tailor-designed drug carriers. Molecular Pharmaceutics 10: 187-198, 2013. (PMID: 23244299)
Lu, J., Huang, Y., Zhao, W., Marquez, R.T., Meng, X., Li, J., Gao, X., Venkataramanan, R., Li, S. PEG-derivatized embelin as a novel nanomicellar carrier for targeted delivery of paclitaxel to breast and prostate cancers. Biomaterials 34: 1591-1600, 2013. (PMID: 23182923)
Li, J., Ghazwani, M., Zhang, Y., Lu, J., Li, J., Fan, J., Gandhi, C.R., and Li, S. miR-122 regulates collagen production via targeting hepatic stellate cells and suppressing P4HA1 expression. Journal of Hepatology 58: 522-528, 2013. (PMID: 23178710)
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. (PMID: 19332088)
Zhang, Q., He, F., Kuruba, R., Gao, X., Wilson, A., Li, J., Billiar, T.R., Pitt, B.R., Xie, W., and Li, S. FXR-mediated regulation of angiotensin type 2 receptor expression in vascular smooth muscle cells. Cardiovascular Research 77: 560-569, 2008. (PMID: 18006431)
Li, J., Wilson, A., Kuruba, R., Zhang, Q., Gao, X., He, F., Zhang, L.M., Pitt, B.R., Xie, W., and Li, S. FXR-mediated regulation of eNOS expression in vascular endothelial cells. Cardiovascular Research 77: 169-177, 2008. (PMID: 18006476)
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. (PMID: 16357303)
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 13: 510-518, 2005. (PMID: 15953766)
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). (PMID: 15382053)
Yang, L., Li, J., Zhou, W., Yuan, X., and Li, S. Targeted delivery of antisense oligodeoxynucleotides to folate receptor-overexpressing tumor cells. Journal of Controlled Release 95: 321-331, 2004. (PMID: 14980780)
R01CA278608-01 Nanoparticles-Mediated Combination Therapy for Breast Cancer
PI: Song Li,
05/01/23-04/30/28
R01CA270623-A1 Combination Therapy for Pancreatic Cancer
PI: Song Li
04/01/23-03/30/28
RO1CA239716 Study of Interleukin 33 as A New Immunotherapy of Lung Cancer
PI: Binfeng Lu (contact PI) & Song Li (co-PI)
07/01/19-06/30/24
