Dr. Li is the David and Betty Brenneman Professor in the Department of Pharmaceutical Sciences and Director of the Center for Pharmacogenetics at the University of Pittsburgh School of Pharmacy. He is an elected Fellow of the American Institute for Medical and Biological Engineering (AIMBE). Dr. Li received his M.D. and Ph.D. from the Fourth Military Medical University in Xi’an, China, and completed his postdoctoral training with Dr. Leaf Huang. He joined the faculty of the University of Pittsburgh School of Pharmacy in 2000.
Dr. Li has broad expertise in medicine, biology, immunology, and drug and gene delivery. He is the author or co-author of more than 190 peer-reviewed publications and 36 review articles and book chapters. He serves on the editorial boards of several scientific journals and frequently serves on review panels for the NIH, DOD, VA, and other funding agencies.
Research in Dr. Li’s laboratory has been continuously supported by grants from multiple funding agencies, including the NIH, DOD, and other funding agencies.
Dr. Li has established a strong research program at the interface of biology, immunology, and biotechnology. His laboratory has developed several innovative delivery systems to address major challenges in drug and gene therapy, combining fundamental studies of drug formulation with comprehensive structure–activity relationship (SAR) investigations. His group introduced the concept of "new amphiphilic surfactants with interfacial drug-interactive motifs," enabling the formulation of numerous previously "hard-to-formulate" drugs (Molecular Pharmaceutics, 2013; Biomaterials, 2015).
Another major advance from Dr. Li's group has been the development of ultrasmall nanocarriers for cancer therapy (Theranostics, 2020; Biomaterials, 2021; Materials Today, 2023). The group discovered that covalent conjugation of nucleoside-based drugs—including gemcitabine, azacitidine, cytarabine, and decitabine—to an amphiphilic polymeric carrier can dramatically reduce nanoparticle size, from approximately 150 nm to 15 nm. These ultrasmall nanocarriers effectively co-deliver a broad range of water-soluble and water-insoluble therapeutics, and their diminutive size may help overcome the limited tumor accumulation and penetration that have long challenged nanomedicine in cancer patients. More recently, Dr. Li's group developed a novel delivery system that achieves efficient tumor accumulation and deep tumor penetration through CD44-mediated targeting of tumor endothelial cells (TECs), followed by transcytosis across the TEC layer and sequential transcytosis through multiple layers of tumor cells (Nature Nanotechnology, 2023; Nature Communications, 2024). This platform can deliver small molecules or nucleic acids individually, or in combination.
Dr. Li's group has also developed a new class of nucleic acid delivery systems based on nucleoside-enhanced polymeric carriers. Incorporating a nucleoside—either therapeutic or inert—into the carrier provides additional carrier–nucleic acid interactions through hydrogen bonding and π–π stacking. This design reduces the amount of cationic material required, potentially minimizing toxicity, while also enabling co-delivery of nucleic acids alongside nucleoside-based therapeutics (Nature Communications, 2025 and 2026). In a complementary effort to develop lipid-based systems for nucleic acid delivery, the group has also developed a series of novel β-triketone-based ionizable cationic lipids using a simple and efficient click-chemistry approach (Advanced Science, 2026).
Beyond delivery system design, Dr. Li's group has investigated mechanisms underlying resistance to cancer chemotherapy and immunotherapy. His laboratory identified glutamate metabotropic receptor 4 (GRM4) as a novel negative regulator of antitumor immunity across multiple tumor models (Science Advances, 2021). More recently, the group identified Xkr8 as a gene critical to chemotherapy-induced immune suppression and cancer relapse, laying the groundwork for a potential combination therapeutic strategy targeting Xkr8 (Nature Nanotechnology, 2023).
Dr. Li's research program also extends beyond cancer to nonmalignant diseases, including cardiovascular and liver diseases, with a focus on developing improved delivery systems and identifying novel therapeutic targets.
Chen, S., Zhang, H., Mu, Y., Chen, C.-Y., Dabiri, S., Zhang, B., Li, S., Huang, Y., Wang, X., Xu, Y., Wang, Z., Bain, D.J., Yang, D., and Li, S. Targeting chemotherapy-induced CD200 via a nucleoside-enhanced nanocarrier for cancer immunochemotherapy. Nature Communications (in press)
Chen, S., Li, S., Luo, Z., Huang, Y., Zhang, H., Mu, Y, Zhang, B., Chen, C.Y., Hou, G., Zhang, M., and Li, S. Nanocarrier-mediated targeting of chemotherapy-induced DPP4 enhances T cell infiltration and improves cancer immunochemotherapy. Bioactive Materials 2027; 67: 95-113.
Li, H., Tang, H., Mu, Y., Chen, S., Floreancig, P.E., Wang, J., Huang, Y., and Li, S. β-triketone-based ionizable cationic lipids synthesized via click chemistry for siRNA delivery. Advanced Science 2026: e15482 (PMID: 41911333).
Huang, H., Mu, Y., Huang, Y., Ji, B., Wang, Y., Chen, C.Y., Chen, Y., Luo, Z., Li, S., Ziqian Zhang, Z., Wang, L., Conway, J.F., Yang, D., *Wang, J., *Sun, J., and *Li, S. Rational development of gemcitabine-based nanoplatform for targeting SERPINB9/Granzyme B axis to overcome chemo-immune-resistance. Nature Communications 2025; 16: 4176 (PMID: 40325025).
Luo, Z., Chen, C.Y. and Li, S. Improving tumor targeting and penetration for nanoparticles-mediated cancer therapy. Small Methods (in press).
Huang, H., Ji, B., Huang, Y., Li, S., Luo, Z., Chen, S., Li, S., Chen, Y., Bain, D.J., Sun, J., Yang, D., Burns, T.F., Wang, J., and Li, S. Advanced hierarchical computational modeling-based rational development of platinum (II) nanocomplex to improve lung cancer therapy. Advanced Functional Materials (in press).
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., Venkataramanan, 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-over expressing tumor cells. Journal of Controlled Release 95: 321-331, 2004. (PMID: 14980780)
R01CA278608 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
R01CA295774 Targeting iRhom to Improve Colon Cancer Immunochemotherapy
PI: Song Li
01/01/25-12/31/29
R01CA309823 Novel Targeted Combinatorial Therapy for Castration-resistant Prostate Cancer
Contact PI: Qiming Jane Wang; co-PT: Song Li
03/18/26-02/28/31
CA315252 Non-Small Cell Lung Cancer Nanotherapy Targeting STRAP
Contact PI: Pran Datta; co-PT: Song Li
09/07/26-08/31/31
