Duxin Sun, PhD
Dr. Duxin Sun is a Professor in the Department of Pharmaceutical Sciences and J G Searle Endowed Professor in the College of Pharmacy at the University of Michigan. Dr. Sun serves as the Director of Pharmacokinetics (PK) Core. Dr. Sun also has joint appointment in the Chemical Biology program, the Interdisciplinary Medicinal Chemistry program, and University of Michigan’s Comprehensive Cancer Center.
Dr. Sun has published more than 180 papers, 100 meeting abstracts, 10 book chapters, and 12 U.S. patents. Dr. Sun has supervised 29 PhD students and 40 postdoctoral fellows and visiting scientists. Dr. Sun is a Fellow of American Association of Pharmaceutical Scientists (AAPS) and has served as chair of the PPB (Physical Pharmacy and Biopharmaceutics) section in AAPS; Dr. Sun serves on FDA Pharmaceutical Science and Clinical Pharmacology Advisory Committee. Dr. Sun is the Vice president of the American Chinese Pharmaceutical Association (ACPA). Dr. Sun has served on study sections for NIH, FDA, Cancer Research UK, French National Research Agency, and Italian Ministry of Health.
Dr. Sun’s research interests focus on drug discovery and nanomedicine for cancer therapeutics. Specifically, his lab is currently working on: (1) Nanoparticles for drug and vaccine delivery; (2) Novel cancer targets and drug discovery; (3) Cancer stem cells and therapeutics; (4) Drug optimization alters tissue targeting, efficacy and toxicity; (5) Intubation and wireless sampling device in Gut for drug optimization and microbiome analysis.
Breast Cancer Stem Cells and Therapeutics
The goal of this project is to visualize the cancer stem cells hierarchy to answer questions for how heterogeneous breast cancer cells are generated by breast cancer stem cells? How chemotherapy alters heterogeneity by changing breast cancer stem cells? Why chemotherapy can not “cure” cancer? How to identify drugs or targets to eliminate different populations of heterogeneous cancer cells in order to “cure” cancer.
Drug Discovery to Treat P53/PTEN Deficient Triple Negative Breast Cancer
Among four types of breast cancers, triple negative breast cancer (TNBC) still lacks treatment options. Triple negative breast cancer (TNBC) exhibits high frequencies of p53 and PTEN genetic aberrations, with 84% and 35%, respectively, which is associated with metastasis, low therapeutic response, and poor prognosis. However, the concurrent p53/PTEN deficiency in TNBC is not actionable due to the lack of molecular targets. The goal of this project is to identify specific therapeutic target for drug discovery to treat P53/PTEN deficient TNBC.
Drug Optimization Alters Tissue Targeting, Efficacy and Toxicity
In drug development process, 90% drugs fail from phase I to phase III trials due to lack of efficacy (30-40%), toxicity (30%), poor drug like properties (15-20%), and lack of commercial needs (10%). The goal of this project is to investigate the failure of drug development (lack of efficacy or toxicity) is due to biological potency or tissue targeting. Why modifications in similar structures (with same target) alters tissue targeting, efficacy and toxicity? How to predict or screen tissue targeting to increase success rate of clinical trials in drug discovery? How do drugs distribute in the heterogeneous tumor tissues by MS-Imaging?
Nanotechnology for Drug Delivery
More than 90% nanomedicines failed in clinical trials. Some successful nanomedicines may have only compared combination nanomedicine with standard care to standard care alone, without comparison with free drugs (with few exceptions). The goal of this project is to investigate why most of Injectable nanomedicines failed to improve efficacy, but only alter toxicity, and how to design future nanomedicine to enhance the success rate.
Nanosatellite (VLN) Mimics Viral-Like Structure to Activate Both T Cell and B Cell Immunity
Most cancer vaccines failed in clinical trials due to the lack of durable long term clinical anticancer efficacy. In contrast, viral-like particle (VLP) vaccines (such as HPV vaccine) are effective to prevent virus infection through activation of B cell immunity in addition to T cell immunity. However, it is very challenging to generate VLP vaccine as anticancer vaccine. The goal of this project is to generate inorganic viral-like nanoparticle to mimic viral like structure as T cell or B cell vaccines.
Intubation and Wireless Sampling Device in Gastrointestinal Track For Microbiome Analysis and Drug Product Optimization
Gut microbiome has been shown to regulate immunity, cancer, and metabolic disease. The most gut microbiome is usually analyzed from feces, which is different from microbiome in small intestine. However there is lack of information for GI microbiome in small intestine due to the lack of sampling methods.
In addition, during oral drug product development, in vitro and in vivo drug dissolution needs to be optimized. However, there is lack of data and understanding of dissolution in GI tract for oral drug product development and optimization.
The goal of this project is to develop method by intubation or wireless sampling device to obtain samples from whole GI tract (stomach, duodenum, jejunum, ileum, and colon) for GI microbiome analysis and drug dissolution analysis.
Tan YS, Sansanaphongpricha K, Xie Y, Donnelly CR, Luo X, Heath BR, Zhao X, Bellile EL, Hu H, Chen H, Polverini PJ, Chen Q, Young S, Carey TE, Nör JE, Ferris RL, Wolf G, Sun D, Lei YL. Mitigating SOX2-potentiated immune escape of head and neck squamous cell carcinoma with a STING-inducing nanosatellite vaccine. Clin Cancer Res. 2018 May 16. [Epub ahead of print] PMID: 29769207
Moody RR, Lo MC, Meagher JL, Lin CC, Stevers NO, Tinsley SL, Jung I, Matvekas A, Stuckey JA, Sun D. Probing the interaction between the histone methyltransferase/deacetylase subunit RBBP4/7 and the transcription factor BCL11A in epeigenetic complexes. J Biol Chem. 2018 Feb 9;293(6):2125-2136. PMCID: PMC5808772
Koenigsknecht MJ, Baker JR, Wen B, Frances A, Zhang H, Yu A, Zhao T, Tsume Y, Pai MP, Bleske BE, Zhang X, Lionberger R, Lee A, Amidon GL, Hasler WL, Sun D. In vivo dissolution and systemic absorption of immediate release ibuprofen in human gastrointestinal tract under fed and fasted conditions. Mol Pharm. 2017 Dec 4;14(12):4295-4304. PMID: 28937221
Burnett JP, Lim G, Shah RB, Lim R, Paholak HJ, McDermott SP, Sun L, Tsume Y, Bai S, Wicha MS, Sun D, Zhang T. Sulforaphane enhances the anticancer activity of taxanes against triple negative breast cancer by killing cancer stem cells. Cancer Lett. 2017 May 28;394:52-64. PMID: 28254410
Sansanaphongpricha K, DeSantis MC, Chen H, Cheng W, Sun K, Wen B, Sun D. Multibuilding block Janus synthesized by seed-mediated self-assembly for enhanced photothermal effects and colored Brownian motion in an optical trap. Small. 2017 Feb;13(6):1603569. PMID: 27873448
Paholak HJ, Stevers NO, Chen H, Burnett JP, He M, Korkaya H, McDermott SP, Deol Y, Clouthier SG, Luther T, Li Q, Wicha MS, Sun D. Elimination of epithelial-like and mesenchymal-like breast cancer stem cells to inhibit metastasis following nanoparticle-mediated photothermal therapy. Biomaterials. 2016 Oct;104:145-57. PMID: 27450902
Sun L, Burnett JP, Gasparyan M., Xu F, Jiang H, Lin C-C, Myers I, Korkaya H, Liu Yajing, Connarn J, He H, Zhang N, Wicha MS, Sun D. Novel cancer stem cell targets during epithelial to mesenchymal transition in PTEN-deficient trastuzumab-resistant breast cancer. Oncotarget. 2016 Aug 9;7(32):51408-51422. PMCID: PMC5239484
Yanyan Li, Tao Zhang, Hasan Korkaya, Suling Liu, Yanke Yu, Hsiu-Fang Lee, Bryan Newman, Shawn G. Clouthier, Steven J. Schwartz, Max S. Wicha, and Duxin Sun. Sulforaphane, a Dietary Component of Broccoli/Broccoli Sprouts, Inhibits Breast Cancer Stem Cells. Clinical Cancer Research, 2010,16: 2580-90.