Biopharmaceutical Sciences track
Department of Pharmaceutical Sciences
Thomas J. Long School of Pharmacy
University of the Pacific
Stockton, California
USA

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 and modulating the function of the aryl hydrocarbon receptor involving protein-protein and protein-DNA interactions; (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 disease treatment.


Current Lab Members:

William Chan (PI) 

Sandra Do (PhD student, since 1/2020)

Dan Shao (PhD student, since 9/2020)

Yiyuan "Sky" Wang (PhD student, since 9/2020)

Sophia Wong (PharmD/PhD student, since 1/2022)

Brandon Huynh (PharmD student, since 5/2024)

Eric Xing (PharmD student, since 5/2024)

Former Members:

Postdocs:

Depeng Wang (Postdoc, 2008-2011)

Yanjie Li (Postdoc, 2008-2011)

Pompeya Bhattacharya (Postdoc, 2007-2011)

Annie Shinn (Postdoc, 2007-2008)

Grad Students:

Rui Xiong (PhD, 2023)

Yiyuan Sky Wang (MS, 2022)

Junyu "Elizabeth" Qian (MS, 2022)

Yujie Yang (PhD, 2021)

Jinyun Chen (PhD, 2020)

Poonam Yakkundi (PhD, 2018)

Beverly Pappas (PhD, 2018)

Sravanthi Tejomurthula (MS, 2017)

Himaja Ponnakanti (MS, 2017)

John Thompson (MS Biology, 2015)

Jinghang (Alic) Xie (PhD, 2014)








Yu Wang (PhD, 2013)

Tianmin (Ivy) Zhang (MS, 2010)

Tony Luu (PhD, 2008)

Chandra Bunton (MS, 2008)

Yi Li (PhD, 2006)

Xiaodong Wang (PhD, 2006)

Kyle Jensen (PhD, 2006)







Elvina Jahja (MS, 2004)
Premnath Shetty (PhD, 2002)
Anthony B. Delucchi (MS, 2001)
Bhagyashree Bhagwat (MS, 2001)
Maria E. Cordeiro (MS, 1997)




Others:

James O'Dell (high school student, Summer 2024)

Laurence Allen (high school student, summer 2019)

Diego Bustamante (high school student, summer 2019)

Arta Gharib Parsa (research assistant, summer 2016)

Lina Ren (visiting scientist, since 7/2014 - 2/2016)

Minh Phuong Nguyen (visiting scientist, 2008-2010)

Jingjun Jin (visiting scholar, 2008)










Pharmacy and Undergraduate Research:

Vu Nguyen (Pharm.D., 2026) - one semester

Zeenat Entezar (Pharm.D., 2026), two semesters

Christy Xiong (Pharm.D., 2026), two semesters

Sunny Kler (Pharm.D., 2025) - two semesters

Jamie Trocke (Pharm.D., 2025) - two semesters

Stephen Nguyen (Pharm.D., 2024) - two semesters

Jeffrey Chen (Pharm.D., 2023) - two semesters 

Victor Tran (Pharm.D., 2023) - two semesters

Dan Shao (BS, Biochem, 2020) - one semester  

Colby Giang (Pharm.D., 2021) - four semesters

Michelle She (Pharm.D., 2021) - four semesters

Michelle Su (Pharm.D., 2021) - three semesters

Amanda Yee (Pharm.D., 2021) - two semesters

Brandon Truong (Pharm.D., 2021) - one semester

Wynonna Abigail Fuentez (Pharm.D., 2021) - one semester

Reina Marie Sanz (Pharm.D., 2022) - one semester

Derek Cheung (Pharm.D., 2022) - one semester

Annie Lee (Pharm.D., 2021) - three semesters

Franchesca Soe (Pharm.D., 2021) - three semesters

Michael Remmel (Pharm.D., 2021) - three semesters

Stephanie Luu (Pharm.D., 2020) - four semesters

Connie Nguyen (Pharm.D., 2020) - four semesters

Kenny Ngo (Pharm.D., 2020) - five semesters

Kyra Gong (Pharm.D., 2020) - six semesters

Michael Luo (Pharm.D., 2020) - six semesters

Keane Virola (Pharm.D., 2021) - one semester

Arjun Patel (Pharm.D., 2020) - one semester

Nayoung Kang (Pharm.D., 2019) - three semesters

Jenny Truong (Pharm.D., 2019) - four semesters

Hana Lee (Pharm.D., 2019) - four semesters

Vivian Tran (Pharm.D., 2019) - five semesters

Jessica Nguyen (Pharm.D., 2019) - five semesters

Vivian Wang (pre-pharmacy undergrad student) - two semesters

Christina Nyaung (Pharm.D., 2018) - four semesters 

Joshua Lin (Pharm.D., 2018) - six semesters

Genevieve Cheung (Pharm.D., 2018) - seven semesters

Kyle Kwong (Pharm.D., 2018) - two semesters

Scott Leong (Pharm.D., 2017) - four semesters 

Cory Ng (Pharm.D., 2017) - five semesters

Tiffany Chang (Pharm.D., 2017) - five semesters

Amanda Spickenreuther (Pharm.D., 2019) - three semesters

Stephanie Ly (Pharm.D., 2017) - four semesters

Viral Panchal (Pharm.D., 2017) - one semester

Wyatt Good (Pharm.D., 2017) - one semester

Sarah Sung (Pharm.D., 2016) - two semesters

Michael Cheung (Pharm.D., 2016) - four semesters

Katie Ngo (Pharm.D., 2016) - five semesters 

Jackie Chong (Pharm.D., 2016) - five semesters

Alex Oon (Pharm.D., 2018) - one semester

Krystal Tai (Pharm.D., 2015) - five semesters

Quoc Sinh Le (Pharm.D., 2015) - five semesters

Kyung Kim (Pharm.D., 2015) - three semesters

Hee Jae (Janet) Chung (Pharm.D., 2016) - two semesters

Joshua Tai (Pharm.D., 2016) - one semester

Stephanie Dias (BS, Biol Sci, 2014) - one semester

Stephanie Lee (Pharm.D., 2015) – one semester

Dimi Rynsburger (Pharm.D., 2014) – three semesters

Allison Li (Pharm.D., 2014) – two semesters

John Thompson (undergrad, Biochem BS, Spring 2013) – four semesters

Alex Kang (Pharm.D., 2013) – two semesters
Mark Smaili (Pharm.D., 2013) – two semesters
Hong (Emiley) Phan (Pharm.D., 2012) – three semesters

Abraham Chang (Pharm.D., 2012) – five semesters








Paula Erezo (Pharm.D., 2011) – one semester
Timothy Chow (Pharm.D., 2011) – two semesters
Priti Patel (Pharm.D., 2009) – one semester
Betty Huang (undergrad, 2008) – one  semester
Steve Andreessen (undergrad, 2008) – one semester
Jason Zarifis (Pharm.D., 2007) – one semester
Barry Peterson (Pharm.D., 2004) – two semesters
Paula Phongsamran (Pharm.D., 2001) – one semester
Steven Nguyen (Pharm.D., 2001) – three semesters
Emily Ha (Ph.D. candidate, 2001) – one semester
Yvonne Chen (Pharm.D., 2000) – one semester
Loc Nguyen (BS, Biology, 2000) – four semesters
Calvin Tong (Pharm.D., 1999) – one semester
Gianni Abate (BS, Biology, 1998) – one semester
Xuan Nguyen (BS, Biology, 1998) – one semester
Anthony Delucchi (BS, Biology, 1998) – two semesters 

Publications at Pacific:
1. Xiong, R., Shao, D., Do, S., and Chan, W. K. (2023) Activation of chaperone-mediated autophagy inhibits the aryl hydrocarbon receptor function by degrading this receptor in human lung epithelial carcinoma A549 cells, Int. J. Mol. Sci. 24, 15116. https://pubmed.ncbi.nlm.nih.gov/37894798/

2. Estari, R. K., Dong, J., Chan, W. K., Park, M. S. and Zhou, Z. (2021) Time effect of rutaecarpine on caffeine pharmacokinetics in rats, Biochem. Biophys. Rep. 28, 101121. 

3. Yang, Y. and Chan, W. K. (2021) Glycogen synthase kinase 3 beta regulates the human aryl hydrocarbon receptor cellular content and activity, Int. J. Mol. Sci. 22, 6097. https://pubmed.ncbi.nlm.nih.gov/34198826/

4. Chen, J., Yang, Y. Russu, W. A. and Chan, W. K. (2021) The aryl hydrocarbon receptor undergoes chaperone-mediated autophagy in triple-negative breast cancer cells, Int. J. Mol. Sci. 22, 1654. https://pubmed.ncbi.nlm.nih.gov/33562118/

5. Yang, Y. and Chan, W. K. (2020) Selective autophagy maintains the aryl hydrocarbon receptor levels in HeLa cells: a mechanism that is dependent on the p23 co-chaperone, Int. J. Mol. Sci. 21, 3449. https://pubmed.ncbi.nlm.nih.gov/32414129/
6. Yakkundi, P., Gonsalves, E., Galou-Lameyer, M., Selby, M. J. and Chan, W. K. (2019) Aryl hydrocarbon receptor acts as a tumor suppressor in a syngeneic MC38 colon carcinoma tumor model, Hypoxia 7, 1-16.  https://pubmed.ncbi.nlm.nih.gov/31119183/
7. Chen, J., Yakkundi, P. and Chan, W. K. (2019) Down-regulation of p23 in normal lung epithelial cells reduces toxicities from exposure to benzo[a]pyrene and cigarette smoke condensate via an aryl hydrocarbon receptor-dependent mechanism, Toxicol. Sci. 167, 239-248. https://pubmed.ncbi.nlm.nih.gov/30204910/
8. Miller, M., Pal, A., Albusairi, W., Joo, H., Pappas, B., Tuhin, M. T. H., Liang, D., Jampala, R., Liu, F., Khan, J., Faaij, M., Park, M., Chan, W., Graef, I., Zamboni, R., Kumar, N., Fox, J., Sinha, U. and Alhamadsheh, M. (2018) Enthalpy-driven stabilization of transthyretin by AG10 mimics a naturally occurring genetic variant that protects from transthyretin amyloidosis, J. Med. Chem. 61, 7862-7876. https://pubmed.ncbi.nlm.nih.gov/30133284/
9. Pappas, B., Yang, Y., Wang, Y., Kim, K., Cheung, M., Ngo, K., Shinn, A. and Chan, W. K. (2018) p23 protects the human aryl hydrocarbon receptor from degradation via a heat shock protein 90-independent mechanism, Biochem. Pharmacol. 152, 34-44. https://pubmed.ncbi.nlm.nih.gov/29555469/
10. Ren, L., Thompson, J. D., Cheung, M., Ngo, K., Sung, S., Leong, S. and Chan, W. K. (2016) Selective suppression of the human aryl hydrocarbon receptor function can be mediated through binding interference at the C-terminal half of the receptor, Biochem. Pharmacol. 107, 91-100. https://pubmed.ncbi.nlm.nih.gov/26970402/
11. Zheng, Y., Xie, J., Huang, X., Dong, J., Park, M. S. and Chan, W. K. (2016) Binding studies using Pichia pastoris expressed human aryl hydrocarbon receptor and aryl hydrocarbon receptor nuclear translocator proteins, Prot. Exp. Purific. 122, 72-81.  https://pubmed.ncbi.nlm.nih.gov/26923060/
12. Penchala, S. C., Miller, M. R., Pal, A., Dong, J., Madadi, N. R., Xie, J., Joo, H., Tsai, J., Batoon, P., Samoshin, V., Franz, A., Cox, T., Miles, J., Chan, W. K., Park, M. S. and Alhamadsheh, M. M. (2015) A Biomimetic approach for enhancing the in vivo half-life of peptides, Nat. Chem. Biol. 11, 793-8. 
13. Malla, R., Wang, Y., Chan, W. K., Tiwari, A. K. and Faridi, J. S. (2015) Genetic ablation of PRAS40 improves homeostasis via linking the AKT and mTOR pathways, Biochem. Pharmacol. 96, 65-75.
14. Gao, X., Bhattacharya, S., Chan, W. K., Jasti, B. R., Upadrashta, B. and Li, X. (2014) Expression of p-glycoprotein and CYP3A4 along the porcine oral-gastrointestinal tract: implications on oral mucosal drug delivery, Drug Dev. Ind. Pharm. 40, 599-603.
15. Xie, J., Huang, X., Park, M. S., Pham, H. M. and Chan, W. K. (2014) Differential suppression of the aryl hydrocarbon receptor nuclear translocator-dependent function by an aryl hydrocarbon receptor PAS-A-derived inhibitory molecule, Biochem. Pharmacol. 88, 253-65.
16. Penchala, S. C., Connelly, S., Wang, Y., Park, M. S., Zhao, L., Baranczak, A., Rappley, I., Vogel, H., Liedtke, M., Witteles, R. M., Powers, E. T., Reixach, N., Chan, W. K., Wilson, I. A., Kelly, J. W., Graef, I. A. and Alhamadsheh, M. M. (2013) AG10 inhibits amyloidogenesis and cellular toxicity of the familial amyloid cardiomyopathy associated V122I transthyretin, Proc. Natl. Acad. Sci. USA 110, 9992-7.

17. 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.
18. 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.
19.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.
20. 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.
21. 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.
22. 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.
23. 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.
24. 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.
25. 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.
26. 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.
27. 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.
28. 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.
29. 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.
30. 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.
31. 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.
32. 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.
33. 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.
34. 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.
35. 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.
36. 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.
37. 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.
38. (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.
39. 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.
40. 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.
41. 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.
42. 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.

Funding Agency:
National Institutes of Health
University of the Pacific internal funds

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