Duxin Sun, PhD
North Campus Research Complex
1600 Huron Parkway
Ann Arbor, MI 48109-1600
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Summary
Dr. Duxin Sun is the Associate Dean for Research, the Charles Walgreen Jr. Professor of Pharmacy and Pharmaceutical Sciences in the College of Pharmacy at the University of Michigan. He serves as the Director of the Pharmacokinetics (PK) Core. Dr. Sun also has a joint appointment in the Chemical Biology program, the Interdisciplinary Medicinal Chemistry program, and University of Michigan's Comprehensive Cancer Center.
Dr. Sun’s research interests focus on drug development, cancer nanomedicine, cancer vaccine, and pharmacokinetics. Dr. Sun established the STAR system (Structure-Tissue/Cell Selectivity-Activity Relationship) to enhance drug development success rate by addressing the 90% failuar rate. He designed albumin based nanomedicines to enhance clinical efficacy of immuno-oncology drugs by targeting immune cells in the lymphatic system and tumors. He also developed SARS-CoV-2 B epitope-guided neoantigen peptide or mRNA vaccines to enhance their efficacy by activating CD4/CD8 T cell immunity through B cell-mediated antigen presentation.
Dr. Sun earned his BS in Pharmacy, MS in Pharmacology, and PhD in Pharmaceutical Sciences, and has also received training in Molecular Biology as a visiting scientist. With research experience in both academia and the pharmaceutical industry, Dr. Sun has published over 280 papers, and has mentored 40 PhD students and 75 postdoctoral fellows/visiting scientists. Dr. Sun is an elected Fellow of both the American Association for the Advancement of Science (AAAS) and the American Association of Pharmaceutical Scientists (AAPS). He has served on the FDA Pharmaceutical Science and Clinical Pharmacology Advisory Committee and participated in study sections for the NIH and FDA.
Dr. Sun's administrative Specialist is Erika Zucal - [email protected].
Feature Story
Will AI revolutionize drug development- game changer or nonsense?The potential of using artificial intelligence in drug discovery and development has sparked both excitement and skepticism among scientists, investors and the general public. “Artificial intelligence is taking over drug development,” claim some companies and researchers. Over the past few years, interest in using AI to design drugs and optimize clinical trials has driven a surge in research and investment. AI-driven platforms like AlphaFold, which won the 2024 Nobel Prize for its ability to predict the structure of proteins and design new ones, showcase AI’s potential to accelerate drug development. AI in drug discovery is “nonsense,” warn some industry veterans. They urge that “AI’s potential to accelerate drug discovery needs a reality check,” as AI-generated drugs have yet to demonstrate an ability to address the 90% failure rate of new drugs in clinical trials. Unlike the success of AI in image analysis, its effect on drug development remains unclear.
Responsibilities
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Associate Dean for Research: UM Pharmacy Professor Research Outreach (UM Pharmacy PRO)
Research Interests
Research (For General Public): Drug Development and NanoMedicine
1. 90% of drugs fail clinical trials – here’s one way researchers can select better drug candidates. Conversation, Feburary 23, 2022
2. Nanoparticles are the future of medicine – researchers are experimenting with new ways to design tiny particle treatments for cancer. Conversation, May 4, 2022
3. Will AI revolutionize drug development? Researchers explain why it depends on how it’s used. Conversation, January 3, 2025
Research (For Scientists): Drug Development, Cancer NanoMedicine, Cancer Vaccine, Pharmacokinetics
1. Why 90% of drug development fails and how to improve it? (PPT Sides, Video Recording)
This project aims to enhance drug development success and efficiency through the STAR-guided drug design of dual targeting PI3Kγ/Sting, PI3Kγ inhibitors, and STING agonists/antagonists, JAK inhibitors for immunotherapy of cancer or autoimmune disease.
2. Why most anticancer nanomedicines do not enhance clinical efficacy and how to improve it ?
This project develops albumin based nanomedicines to enhance clinical efficacy of immuno-oncology drugs (STING agonists and PI3Kγ inhibitors) by targeting immune cells in the lymphatic system and tumors for cancer immunotherapy.
3. How to improve anticancer efficacy of neoantigen mRNA or peptide cancer vaccines?
This project develops SARS-CoV-2 B epitope-guided neoantigen peptide or mRNA cancer vaccine to enhance their anticancer efficacy by activating CD4/CD8 T cell immunity through B cell-mediated antigen presentation.
4. What are the differences of microbiome, bile salts, and drug release in different regions of human GI tract?
This project investigates the differences of the microbiome, bile salts, and drug release among the human stomach, small intestine, and colon, as well as studies how these differences influence drug product development and disease states.
Selected Publications
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Can machine learning overcome the 95% failure rate and reality that only 30% of approved cancer drugs meaningfully extend patient survival? Duxin Sun, Christian Macedonia, Zhigang Chen, Sriram Chandrasekaran, Kayvan Najarian, Simon Zhou7, Tim Cernak, Vicki L. Ellingrod, H.V. Jagadish, Bernard Marini, Manjunath Pai, Angela Violi, Jason C. Rech, Shaomeng Wang, Yan Li1, Brian Athey, Gilbert S. Omenn. J Med Chem, 2024, Sep 10, in press, 10.1021/acs.jmedchem.4c01684
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SARS-CoV-2 B Epitope-Guided Neoantigen NanoVaccines Enhance Tumor-Specific CD4/CD8 T Cell Immunity Through B Cell Antigen Presentation. Chengyi Li, Shuai Mao, Zera Montemayor, Mohamed Dit Mady Traore, Alejandra Duran, Fang Ke, Mahamadou Djibo, Hanning Wen, Wei Gao, Duxin Sun. https://www.biorxiv.org/content/10.1101/2024.07.18.604163v1.
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Machine learning prediction of on/off target-driven clinical adverse events. Albert Cao, Luchen Zhang, Yingzi Bu, and Duxin Sun. Pharmaceutical Research, August, 2024, DOI https://doi.org/10.1007/s11095-024-03742-x
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Antigen-Clustered Nanovaccine Achieves Long-Term Tumor Remission by Promoting B/CD 4 T Cell Crosstalk. Chengyi Li, Ryan Clauson, Luke F. Bugada, Bing He, Hongwei Chen, Hongxiang Hu, Polina Chuikov, Ke Fang, Brett D. Hill, Syed M. Rizvi, Yudong Song, Kai Sun, Daniel Huynh, Marilia Cascalho, Lana Garmire, Leo Yu Lei, Irina Grigorova, Fei Wen, Wei Gao, Duxin Sun. ACS Nano 2024, 18, 13, 9584-9604
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Dual Targeting of STING and PI3Kγ Eliminates Regulatory B Cells to Overcome STING Resistance for Pancreatic Cancer Immunotherapy. Chengyi Li, Shuai Mao, Hongyi Zhao, Miao He, Meilin Wang, Zhongwei Liu, Hanning Wen, Zhixin Yu, Bo Wen, Mahamadou Djibo, Jinsong Tao, Yingzi Bu, Wei Gao, Duxin Sun (Under review in Nature Cancer 2024). bioRxiv doi: https://doi.org/10.1101/2024.02.14.580378
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A gastrointestinal (GI) locally-activating Janus Kinae (JAK) inhibitor to treat ulcerative colitis. Yingzi Bu, Mohamed Dit Mady Traore, Luchen Zhang, Lu Wang, Zhongwei Liu, Duxin Sun. J Biol Chem, 2023, 299: 105467
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CoGT: Ensemble machine learning method and its application on JAK inhibitor discovery. Yingzi Bu, Ruoxi Gao, Bohan Zhang, Luchen Zhang, and Duxin Sun. ACS Omega, 2023, 8, 14, 13232
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Optimization of The Prodrug Moiety of Remdesivir to Improve Lung Exposure/Selectivity and Enhance Anti-SARS-CoV-2 Activity. Hongxiang Hu , Mohamed Dit Mady Traore, Ruiting Li, Hebao Yuan, Miao He, Bo Wen, Wei Gao, Colleen B Jonsson, Elizabeth A Fitzpatrick, Duxin Sun. J Med Chem, 2022, 65, 18, 12044
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Albumin nanoparticle containing a PI3Kγ inhibitor and paclitaxel in combination with α-PD1 induces tumor remission of breast cancer in mice. Yudong Song, Luke Bugada, Ruiting Li, Hongxiang Hu, Luchen Zhang, Chengyi Li, Hebao Yuan, Krishani Rajanayake, Nathan Truchan, Fei Wen, Wei Gao, and Duxin Sun. Science Translational Medicine, 2022, 14 (643): online. DOI: 10.1126/scitranslmed.abl3649
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Why 90% of clinical drug development fails and how to improve it? Duxin Sun, Wei Gao, Hongxiang Hu, Sison Zhou, Acta Pharmaceutica Sinica B, 2022, 12, 3049
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Structure-Tissue Exposure/Selectivity Relationship (STR) Correlates with Clinical Efficacy/Safety. Wei Gao, Hongxiang Hu, Lipeng Dai, Miao He, Hebao Yuan, Huixia Zhang, Jinhui Liao, Bo Wen, Yan Li, Maria Palmisano, Mohamed Dit Mady Traore, Simon Zhou, Duxin Sun. Acta Pharmaceutic Sinica B, 2022, 12, 2462
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What went wrong with anticancer nanomedicine design and how to make it right. D Sun, S Zhou, W Gao. ACS nano, 2020, 14 (10), 12281-12290
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Reappraisal of anticancer nanomedicine design criteria in three types of preclinical cancer models for better clinical translation. X Luan, H Yuan, Y Song, H Hu, B Wen, M He, H Zhang, Y Li, F Li, P Shu, ... Biomaterials, 2021, 120910
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Combined p53-and PTEN-deficiency activates expression of mesenchyme homeobox 1 (MEOX1) required for growth of triple-negative breast cancer. M Gasparyan, MC Lo, H Jiang, CC Lin, D Sun. Journal of Biological Chemistry, 2020, 295 (34), 12188-12202
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Remdesivir for treatment of COVID-19: combination of pulmonary and IV administration may offer additional benefit. D Sun. 2020, The AAPS journal 22, 1-6
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Albumin nanoparticle of paclitaxel (abraxane) decreases while taxol increases breast cancer stem cells in treatment of triple negative breast cancer. H Yuan, H Guo, X Luan, M He, F Li, J Burnett, N Truchan, D Sun. Molecular Pharmaceutics, 2020, 17 (7), 2275-2286
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Neonatal Fc Receptor (FcRn) Enhances Tissue Distribution and Prevents Excretion of nab-Paclitaxel. F Li, H Yuan, H Zhang, M He, J Liao, N Chen, Y Li, S Zhou, M Palmisano, ... Molecular pharmaceutics, 2019, 16 (6), 2385-2393
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Different Nanoformulations Alter the Tissue Distribution of Paclitaxel, Which Aligns with Reported Distinct Efficacy and Safety Profiles. F Li, H Zhang, M He, J Liao, N Chen, Y Li, S Zhou, M Palmisano, A Yu, .... Molecular pharmaceutics, 2018, 15 (10), 4505-4516
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Spatial and temporal analysis of the stomach and small-intestinal microbiota in fasted healthy humans. AM Seekatz, MK Schnizlein, MJ Koenigsknecht, JR Baker, WL Hasler, .... MSphere, 2019, 4 (2), e00126-19
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Targeting LRP8 inhibits breast cancer stem cells in triple-negative breast cancer. CC Lin, MC Lo, R Moody, H Jiang, R Harouaka, N Stevers, S Tinsley, .... 2018, Cancer letters 438, 165-173
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Mitigating SOX2-potentiated immune escape of head and neck squamous cell carcinoma with a STING-inducing nanosatellite vaccine. YS Tan, K Sansanaphongpricha, Y Xie, CR Donnelly, X Luo, BR Heath, .... Clinical Cancer Research, 2018, 24 (17), 4242-4255
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Probing the interaction between the histone methyltransferase/deacetylase subunit RBBP4/7 and the transcription factor BCL11A in epigenetic complexes. RR Moody, MC Lo, JL Meagher, CC Lin, NO Stevers, SL Tinsley, I Jung, .... Journal of Biological Chemistry, 2018, 293 (6), 2125-2136
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In Vivo Dissolution and Systemic Absorption of Immediate Release Ibuprofen in Human Gastrointestinal Tract under Fed and Fasted Conditions. MJ Koenigsknecht, JR Baker, B Wen, A Frances, H Zhang, A Yu, T Zhao, .... Molecular pharmaceutics, 2017, 14 (12), 4295-4304
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Engineering exosomes as refined biological nanoplatforms for drug delivery. X Luan, K Sansanaphongpricha, I Myers, H Chen, H Yuan, D Sun. Acta Pharmacologica Sinica, 2017, 38 (6), 754-763
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Sulforaphane enhances the anticancer activity of taxanes against triple negative breast cancer by killing cancer stem cells. JP Burnett, G Lim, Y Li, RB Shah, R Lim, HJ Paholak, SP McDermott, .... Cancer Letters, 2017, 394, 52-64
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Measurement of in vivo Gastrointestinal Release and Dissolution of Three Locally Acting Mesalamine Formulations in Regions of the Human Gastrointestinal Tract. A Yu, JR Baker, AF Fioritto, Y Wang, R Luo, S Li, B Wen, M Bly, Y Tsume, .... Molecular pharmaceutics, 2017, 14 (2), 345-358
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Multibuilding Block Janus Synthesized by Seed‐Mediated Self‐Assembly for Enhanced Photothermal Effects and Colored Brownian Motion in an Optical Trap. K Sansanaphongpricha, MC DeSantis, H Chen, W Cheng, K Sun, B Wen, .... small, 2017, 13 (6), 1602569
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Elimination of epithelial-like and mesenchymal-like breast cancer stem cells to inhibit metastasis following nanoparticle-mediated photothermal therapy. HJ Paholak, NO Stevers, H Chen, JP Burnett, M He, H Korkaya, .... Biomaterials, 2016, 104, 145-157
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Novel cancer stem cell targets during epithelial to mesenchymal transition in PTEN-deficient trastuzumab-resistant breast cancer. L Sun, J Burnett, M Gasparyan, F Xu, H Jiang, CC Lin, I Myers, H Korkaya, .... Oncotarget, 2016, 7 (32), 51408
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Sulforaphane, a dietary component of broccoli/broccoli sprouts, inhibits breast cancer stem cells. Y Li, T Zhang, H Korkaya, S Liu, HF Lee, B Newman, Y Yu, SG Clouthier, .... Clinical Cancer Research, 2010, 16 (9), 2580-2590
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Characterization of celastrol to inhibit hsp90 and cdc37 interaction. T Zhang, Y Li, Y Yu, P Zou, Y Jiang, D Sun. Journal of Biological Chemistry, 2009, 284 (51), 35381-35389
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A novel Hsp90 inhibitor to disrupt Hsp90/Cdc37 complex against pancreatic cancer cells. T Zhang, A Hamza, X Cao, B Wang, S Yu, CG Zhan, D Sun. Molecular cancer therapeutics, 2008, 7 (1), 162-170
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Synergistic antipancreatic tumor effect by simultaneously targeting hypoxic cancer cells with HSP90 inhibitor and glycolysis inhibitor. X Cao, M Bloomston, T Zhang, WL Frankel, G Jia, B Wang, NC Hall, .... Clinical Cancer Research, 2008, 14 (6), 1831-1839
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Why is it challenging to predict intestinal drug absorption and oral bioavailability in human using rat model. X Cao, ST Gibbs, L Fang, HA Miller, CP Landowski, HC Shin, .... Pharmaceutical research 2006, 23 (8), 1675-1686
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Comparison of human duodenum and Caco-2 gene expression profiles for 12,000 gene sequences tags and correlation with permeability of 26 drugs. D Sun, H Lennernas, LS Welage, JL Barnett, CP Landowski, D Foster, .... Pharmaceutical research, 2002, 19 (10), 1400-1416
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