Faculty

Duxin Sun

William I. Higuchi Collegiate Professor of Pharmaceutical Sciences

Ph.D., University of Michigan

Research Focus: Chemical biology of protein-protein interactions in cancers; Nanotechnology for cancer imaging and targeted drug delivery; Therapeutics of cancer stem cells; Pharmacokinetics and drug metabolism

Phone: 734.615.8740
E-mail:duxins@med.umich.edu
Fax: 734.936.7675

Dr. Sun’s lab has four research programs.

(A) Drug discovery to block protein-protein interactions in Hsp90 and PRC2 complex for cancer therapy.

The goal for this project is to investigate protein-protein interactions in Hsp90 complex for the regulation of a subset of oncogenic proteins, and to study protein-protein interactions in PRC2 complex for epigenetic histone modification in cancer stem cells. Small molecules are developed to block these protein-protein interactions for cancer stem cell therapeutics.

(B) Nanotheranostics for targeted drug delivery and imaging of cancer stem cells.

The goal of this project is to develop a nanotheranostics (20-50 nm) with multiple “nano satellites” (1-2 nm) on the surface. The nanotheranostics contain an anti-cancer stem cell drug, a cancer stem cell targeting ligand, and an MRI imaging probe. The MRI imaging probe will detect the tumors, then the external laser light will trigger the release of multiple “nano satellites” to penetrate into deep tumor tissues, release payload anticancer drugs, and generate hyperthermia to eliminate cancer stem cells.

(C) Novel cancer stem cells targets and therapeutics of cancer stem cells by natural products.

The goal of this project is to investigate molecular mechanisms (AKT-NF-kB-IL6 positive feedback loop and Meox1 signaling pathway) in cancer stem cells, and to identify natural products to eliminate breast cancer stem cells (BCSC), thereby decreasing metastasis, reducing recurrence, and improving patient survival in triple negative (TNBC) and resistant-Her2+ breast cancers.

(D) Correlation of pharmacokinetics and drug dissolution in vivo in human gastrointestinal tract for locally acting drugs in human clinical trials

The standard bioequivalence (BE) study using plasma pharmacokinetics cannot be used to ensure bioequivalence for gastrointestinal (GI) locally acting and targeted delivery drugs since many factors in the GI tract will change the drug release and dissolution of GI locally acting drugs products. The goal of this project is to study the correlation of pharmacokinetics with in vivo dissolution in local GI tract in vivo for locally acting drugs in human.


Dr. Sun serves as the director of Pharmacokinetics (PK) Core in the University of Michigan.

The Pharmacokinetics (PK) Core has four objectives: (A) To support preclinical pharmacokinetics and metabolism for lead compound selection and dose regimen optimization, which enhances drug discovery & development; (B) To support clinical pharmacokinetics and optimize dose regimen in clinical studies, which supports and increases investigator-initiated clinical trials (phase I and phase II); (C) To increase grants, publications, and patent applications; (D) To train students and postdoctoral fellows with special expertise in DMPK studies.

 

Representative Publications

  1. Jamie N. Connarn, Victoria A. Assimon, Rebecca A. Reed, Eric Tse, Daniel R. Southworth, Erik R. P. Zuiderweg, Jason E. Gestwicki, Duxin Sun. The Molecular Chaperone Hsp70 Activates Protein Phosphatase 5 (PP5) By Binding the Tetratricopeptide Repeat (TPR) Domain. J Biol Chem, 2014, 289:2908-2917.

  2. Hongwei Chen, Joseph Burnett, Fuxiang Zhang, Jiaming Zhang, Hayley Paholak, and Duxin Sun. Highly Crystallized Iron Oxide Nanoparticle as an Effective and Biodegradable Mediator for Photothermal Cancer Therapy"J. Mater. Chem. B, 2013, 2(7): 757-765.

  3. Zou, P., Chen, H., Paholak, H.J., Sun, D., Noninvasive fluorescent resonance energy transfer imaging of in vivo premature drug release from polymeric nanoparticles, Mol Pharm, 2013, 10(11):4185-4195.

  4. Hongwei Chen, Hayley Paholak, Masayuki Ito,  Kanokwan Sansanaphongpricha, Wei Qian, Yong Che, Duxin Sun. Living PEGylation on gold nanoparticles to optimize cancer cell uptake by controlling targeting ligand and charge densities. Nanotechnology, 2013, 24(35):355101.

  5. Bryan Newman, Yan Liu, Hsiu-Fang Lee, Duxin Sun*, Yin Wang*. HSP90 inhibitor 17-AAG selectively eradicates lymphoma stem cells. Cancer Research, 2012: 72(17):4551-61 (*co-corresponding authors)

  6. Li Y, Karagöz GE, Seo YH, Zhang T, Jiang Y, Yu Y, Duarte AM, Schwartz SJ, Boelens R, Carroll K, Rüdiger SG, Sun D. Sulforaphane inhibits pancreatic cancer through disrupting Hsp90-p50(Cdc37) complex and direct interactions with amino acids residues of Hsp90. J Nutr Biochem. 2012, 23: 1617-26.

  7. Zheng N, Zou P, Wang S, Sun D. In Vitro Metabolism of 17-(dimethylaminoethylamino)-17-demethoxygeldanamycin (17-DMAG) in Human Liver Microsomes. Drug Metab Dispos. 2011, 39:627-35.

  8. Yiqun Jiang, Denzil Bernard, Yanke Yu, Yehua Xie, Tao Zhang, Yanyan Li, Joseph Burnett, Xueqi Fu, Shaomeng Wang, and Duxin Sun. Split Renilla Luciferase Protein-Fragment-Assisted Complementation (SRL-PFAC) to Characterize Hsp90/Cdc37 Complex and Identify Critical Residues in Protein-Protein Interactions. J Biol Chem, 2010, 285:21023-36.

  9. 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.

  10. Tao Zhang, Yanyan Li, Yiqun Jiang, Duxin Sun. Characterization of celastrol to inhibit Hsp90 and Cdc37 interaction. J Biol Chem, 2009, 284: 35381-9.

  11. Tao Zhang, Adel Hamza, Xianhua Cao, Bing Wang, Shuwen Yu, Chang-Guo Zhan, Duxin Sun. A Novel Hsp90 inhibitor disrupts Hsp90-Cdc37 complex for pancreatic cancer therapy. Molecular Cancer Therapeutics, 2008, 7: 162-70.

  12. Xianhua Cao, Mark Bloomston, Guang Jia, Wendy L. Frankel, Tao Zhang, Nathan Hall, Hao Cheng, Michael Knopp, and Duxin Sun. Simultaneously Targeting Hypoxic Cancer Cells by HSP90 Inhibitor and Glycolysis Inhibitor in Pancreatic Cancer Therapy. Clinical Cancer Research, 2008; 14: 1831-9.

 

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