Thomas J. Long School of Pharmacy and Health Sciences
University of the Pacific
Research Summary: Our laboratory primarily utilizes biochemical and molecular biological approaches to understand basic cell signaling mechanisms that relate to our response to environmental pollutants, induction of drug metabolizing and glycolytic enzymes, cell cycle control, angiogenesis, and steroid hormone function. Our end goal is to develop therapeutic agents that are effective for treatment of diseases such as cancer. We are interested in (1) studying the protein-protein and protein-DNA interactions in the aryl hydrocarbon receptor signaling pathway; (2) studying the Arnt-dependent signaling cross-talks (involving the aryl hydrocarbon receptor, the hypoxia inducible factor-1 alpha and the estrogen receptor signaling mechanisms) and (3) designing and generating protein therapeutics for cancer treatment, in particularly the solid tumors such as the estrogen receptor-positive breast cancer.
Current Lab Members:
William Chan (PI)
Yu Wang (PhD student, since 9/2008)
Jinghang (Alic) Xie (PhD student, since 9/2008)
Beverly Pappas (PhD student, since 9/2012)
Poonam Yakkundi (Industry PhD student, since 1/2012)
John Thompson (undergrad student)
Dimi Rynsburger (pharmacy student)
Quoc Sinh Le (pharmacy student)
Krystal Tai (pharmacy student)
Stephanie Lee (pharmacy student)
Depeng Wang (Postdoc, 2008-2011)
Yanjie Li (Postdoc, 2008-2011)
Pompeya Bhattacharya (Postdoc, 2007-2010)
Minh Phuong Nguyen (visiting scientist, 2008-2010)
Tianmin (Ivy) Zhang (MS, 2010)
Annie Shinn (Postdoc, 2007-2008)
Jingjun Jin (visiting scholar, 2008)
Tony Luu (PhD, 2008)
Chandra Bunton (MS, 2008)
Yi Li (PhD, 2006)
Xiaodong Wang (PhD, 2006)
Kyle Jensen (PhD, 2006)
Premnath Shetty (PhD, 2002)
Anthony B. Delucchi (MS, 2001)
Bhagyashree Bhagwat (MS, 2001)
Maria E. Cordeiro (MS, 1997)
Publications at Pacific:
1. Wang, Y., Thompson, J. D. and Chan, W. K. (2013) A cell-penetrating peptide suppresses the hypoxia inducible factor-1 function by binding to the helix-loop-helix domain of the aryl hydrocarbon receptor nuclear translocator, Chem.-Biol. Int. 203, 401-11.
2. Nguyen, P. M., Wang, D., Wang, Y., Li, Y., Uchizono, J. A. and Chan, W. K. (2012) p23 co-chaperone protects the aryl hydrocarbon receptor from degradation in mouse and human cell lines, Biochem. Pharmacol. 84, 838-50.
3.Wang, Y., Li, Y., Wang, D., Li, Y., Chang, A., and Chan, W. K. (2012) Suppression of the hypoxia inducible factor-1 function by redistributing the aryl hydrocarbon receptor nuclear translocator from nucleus to cytoplasm, Cancer Lett. 320,111-21.
4. Wang, Y., Yang, D., Chang, A., Zhao, B., Denison, M., Chan, W. K. and Xue, L. (2012) Synthesis of a ligand-quencher conjugate for the ligand binding study of the aryl hydrocarbon receptor using a FRET assay, Med. Chem. Res. 21, 711-21.
5. Park, M. S., Chu, F., Xie, J., Wang, Y., Bhattacharya, P. and Chan, W. K. (2011) Identification of cyclophilin-40 interacting proteins reveals potential cellular function of cyclophilin-40, Anal. Biochem. 410, 257-65.
6. Li, Y., Li, Y., Zhang, T. and Chan, W. K. (2010) The aryl hydrocarbon receptor nuclear translocator-interacting protein 2 suppresses the estrogen receptor signaling via an Arnt-dependent mechanism, Arch. Biochem. Biophys. 502, 121-9.
7. Nguyen, P. M., Park, M. S., Chow, M., Chang, J. H., Wrischnik, L. and Chan, W. K. (2010) Benzo[a]pyrene increases the Nrf2 content by downregulating the Keap1 message, Toxicol. Sci. 116, 549-61.
8. Zhang, T., Wang, X., Shinn, A., Jin, J. and Chan, W. K. (2010) Beta tubulin affects the aryl hydrocarbon receptor function via an Arnt-mediated mechanism, Biochem. Pharmacol. 79, 1125-33.
9. Zhong, S., Bhattacharya, S., Chan, W., Jasti, B. and Li, X. (2009) Leucine-aspartic acid-valine sequences as targeting ligand and drug carrier for doxorubicin delivery to melanoma cells: binding specificity and in vitro cytotoxicity study, Pharm. Res. 26, 2578-87.
10. Wang, D., Faridi, J. S., Li, Y. and Chan, W. K. (2009) A truncated human Ah receptor suppresses growth of human cervical tumor xenografts by interfering with hypoxia signaling, FEBS Lett. 583, 3039-44.
11. Bhattacharya, S., Chan, W. K., Franz, A., Li, X. and Jasti, B. R. (2009) Tumor-targeted drug delivery by folate conjugated amphiphiles, Curr. Trends Biotech. Pharm. 3, 297-310.
12. Luu, T. C., Bhattacharya, P. and Chan, W. K. (2008) Cyclophilin-40 has a cellular role in the aryl hydrocarbon receptor signaling, FEBS Lett. 582, 3167-73.
13. Jensen, J. A. and Chan, W. K. (2006) A truncated Ah receptor blocks the hypoxia and estrogen receptor signaling pathways: a viable approach for breast cancer treatment, Mol. Pharm. 3, 695-703.
14. Li, Y., Luu, T. C. and Chan, W. K. (2005) A novel Arnt-interacting protein Ainp2 enhances the aryl hydrocarbon receptor signaling, Arch. Biochem. Biophys. 441, 84-95.
15. Shetty, P. V., Wang, X. and Chan, W. K. (2004) Cyclosporin A-binding immunophilin 40 (CyP40), but not Hsp70, causes the formation of the aryl hydrocarbon receptor-DNA complex, Arch. Biochem. Biophys. 429, 42-9.
16. Shetty, P. V., Bhagwat, B. Y. and Chan, W. K. (2003) p23 enhances the formation of the aryl hydrocarbon receptor-DNA complex, Biochem. Pharmacol. 65, 941-8.
17. Delucchi, A. B., Jensen, K. A. and Chan, W. K. (2003) Synthesis of 32P-labelled protein probes using a modified thioredoxin fusion protein expression system in Escherichia coli, Biomol. Enginr. 20, 1-5.
18. Chan, W. K. and Delucchi, A. B. (2000) Resveratrol, a red wine constituent, is a mechanism-based inactivator of cytochrome P450 3A4, Life Sci. 67, 3103-12.
19. Lee, A. J., Chan, W. K., Harralson, A. F., Buffum, J. and Bui, B.-C. C. (1999) The effects of grapefruit juice on sertraline metabolism: an in vitro and in vivo study, Clin. Therapeutics 21, 1890-9.
20. Chan, W. K., Gu, Y.-Z. and Bradfield, C. A. (1999) Cross-talk between the aryl hydrocarbon receptor and hypoxia inducible factor signaling pathways. Demonstration of competition and compensation, J. Biol. Chem. 274, 12115-23.
21. Wong, K. M, Chan, W. K., Chan, Y. H. and Li, C. S. (1999) A case report on cefepime toxicity in a renally compromised patient, Nephrol Dial Transplant 14, 2265-6.
22. (Review Article) Li, X and Chan, W. K. (1999) Transport, metabolism and elimination mechanisms of anti-HIV agents, Adv. Drug Delivery Rev. 39, 81-103.
23. Chan, W. K., Nguyen, L., Miller, V. P. and Harris, R. Z. (1998) Mechanism-based inactivation of CYP3A4 by grapefruit juice and red wine. Life Sci. 62, PL135-42.
24. Luo, G., Gu, Y.-Z., Jain, S., Chan, W. K., Carr, K. M., Hogenesch, J. B. and Bradfield, C. A. (1997) Molecular characterization of the murine hif-1 alpha locus, Gene Expression 6, 287-99.
25. Hogenesch, J. B., Chan, W. K., Jackiv, V. H., Brown, R. C., Gu, Y.-Z., Pray-Grant, M., Perdew, G. H. and Bradfield, C. A. (1997) Characterization of a subset of the basic-helix-loop-helix-PAS superfamily that interact with components of the dioxin signaling pathway, J. Biol. Chem. 272, 8581-93.
26. Stauffer, C., Shiotsuki, T., Chan, W. K. and Hammock, B. D. (1997) Characterization of the esterase isozymes of Ips typographus, Arch. Insect Biochem. Phys. 34, 203-21.
National Institutes of Health (1999-2012)
University of the Pacific internal grants