Shiuan Chen, Ph.D.

  • Chair and Professor, Department of Cancer Biology

Shiuan Chen, Ph.D.

Research Focus :
  • Chemoprevention Research Program
  • Breast Cancer Translational Research
  • Program in Natural Therapies
Other Languages Spoken
  • Mandarin
  • 2012 - present, Chair, Department of Cancer Biology, Beckman Research Institute of City of Hope, Duarte, CA
  • 2009 - 2012, Director and Professor, Division of Tumor Cell Biology, Beckman Research Institute of City of Hope, Duarte, CA
  • 2009 - 2012, Associate Chair, Department of Cancer Biology, Beckman Research Institute of City of Hope, Duarte, CA
  • 2002 - 2009, Professor and Director, Division of Tumor Cell Biology, Department of Surgery, City of Hope, Duarte, CA
  • 1994 - 2002, Professor, Department of Immunology, Beckman Research Institute of City of Hope, Duarte, CA
  • 1988 - 1994, Associate Research Scientist, Department of Immunology, Beckman Research Institute of City of Hope, Duarte, CA
  • 1985 - 1988, Assistant Research Scientist, Department of Immunology, Beckman Research Institute of City of Hope, Duarte, CA
  • 1982 - 1985, Research Assistant Professor, School of Pharmacy, University of Southern California, Los Angeles, CA
  • 1981 - 1982, Assistant Researcher, Department of Biochemistry and Biophysics, University of Hawaii
  • 1978 - 1981, Junior Researcher, Department of Biochemistry and Biophysics, University of Hawaii
  • Cancer Biology
  • Program in Natural Therapies

Degrees

  • University of Hawaii, Honolulu, Hawaii, Ph.D., Biochemistry
  • National Taiwan College of Marine Science and Technology, Keelung Taiwan, Republic of China, B.S., Chemistry

Breast Cancer Translation Research

Shiuan Chen, Ph.D., was one of the three investigators who originally isolated the full-length human aromatase cDNA clones. Aromatase is an enzyme that converts androgen to estrogen. Aromatase inhibitors (AIs) are important drugs to treat estrogen-dependent breast cancer. Approximately 60percent of premenopausal and 75 percent of postmenopausal breast cancer patients have estrogen-dependent carcinomas.

Since aromatase is the enzyme responsible for the synthesis of estrogen, and estrogen can have a major effect in the development of breast cancer, an abnormal expression of aromatase in breast cancer cells and/or surrounding adipose stromal cells may have a significant influence on breast tumor development and growth in cancer patients. Aromatase is expressed at higher levels in human breast cancer tissue than in normal breast tissue, as measured by various biochemical assays. During the last 15 years, aromatase inhibitors (AIs) have been demonstrated to be superior to tamoxifen for the treatment of hormonal dependent breast cancer. While this new generation of aromatase inhibitors is shown to be useful in the treatment of hormonal responsive breast cancer, resistance to such endocrine therapy still develops. Through collaboration with Yate-Ching Yuan, Ph.D., (Bioinformatics), we are carrying out gene expression array experiments on AI-responsive as well as resistant cell lines that have been generated in our laboratory. We are identifying and functionally confirming the roles of genes involved in resistance.

These studies will produce valuable molecular information regarding the mechanisms of AI resistance, and the information will help design approaches to reduce resistance and improve the efficacy of AI treatments of breast cancer. Furthermore, our model systems are valuable to test new drugs against endocrine therapy resistance. We are working with several medical and translational research colleagues (Joanne Mortimer, M.D. , Yuan Yuan, M.D., Ph.D., George Somlo, M.D., Laura Kruper, M.D., Courtney Vito, M.D.,Paul Frankel, Ph.D., Tim Synold, Pharm.D.), and Ned Newman, Ph.D. ) to carry preclinical studies in our laboratories and then to design new therapeutic approaches to treat AI resistant breast cancer.

 

Chemoprevention and Superfood Research Program

Since the summer of 2004, Chen and 27 other investigators have initiated an effort to develop a Chemoprevention Research Program at City of Hope. Through biweekly meetings, these Beckman Research Institute of City of Hope researchers and clinicians exchange research information and ideas. Four research areas have recently been chosen to focus on. The immediate goal is to generate preliminary results in these new target areas that will lead to the development of multidiscipline translational chemoprevention research projects at our institution.

Our laboratory has found that grapes, mushrooms and pomegranate contain chemicals that can suppress aromatase activity.  Therefore, a diet containing these "superfoods" would be considered preventative against breast cancer.  We are purifying and characterizing these natural anti-aromatase chemicals and evaluating their in vivo effects using animal experiments. The active chemicals in grapes have been found to be procyanidin dimers that are present at high concentrations in grape seeds. Melanie Palomares, M.D., M.S., (Population Sciences), Jeffrey Weitzel, M.D., (Clinical Cancer Genetics), Tim Synold, Pharm.D., (Experimental Therapeutics) and this laboratory have collaborated and initiated a grape seed extract clinical trial and a mushroom clinical trial based on the chemoprevention studies against breast cancer performed in our laboratory. In addition, experiments have been carried out to show that blueberry contains phytochemicals that can suppress the proliferation and migration of triple negative breast cancer in cell culture and animals.

Furthermore, we have found that mushrooms contain chemicals that act as inhibitors of steroid 5-alpha reductase. Androgen plays a critical role in prostate cancer development.  In the prostate, testosterone (an androgen) is converted to dihydrotestosterone (DHT), an androgen that is even more potent than testosterone. This conversion is catalyzed by the enzyme steroid 5-alpha reductase. An elevation of the steroid 5-alpha reductase activity in the prostate may cause benign prostate hyperplasia (a common problem in older men) and also promote the growth of prostate cancer. Animal experiments have been performed to evaluate the use of these phytochemicals as drugs in the prevention and/or treatment of prostate cancer. One clinical trial designed, based Chen’s findings, is being carried out at City of Hope with Przemyslaw Twardowski, M.D. (Medical Oncology) to evaluate the protective effect of mushroom chemicals against PSA increase in prostate cancer patients. The trial has resulted in two patients with complete response, two patients with partial response, and eight patients with stable PSA response. A recent study in the Chen laboratory has revealed that the intake of mushrooms may reduce the incidence of metabolic diseases such as fatty liver and insulin resistance.

In 2014, with a $2.5 million gift from the Panda Charitable Foundation, a Program in Natural Therapies has been established at City of Hope. This fund supports three lines of research to investigate natural products’ abilities to fight against cancer. Chen is investigating how the foods themselves can improve outcomes of treatment-resistance breast cancer. In addition, the Chen laboratory is generating patient-derived xenograft (PDX) models for novel treatment of breast cancer.

 

Endocrine Disruptor Research

We are also conducting research to determine how environmental chemicals modulate the activity and expression of aromatase in human tissue. Experiments are being conducted to provide a molecular and mechanistic basis as to how phytochemicals and organochlorine compounds affect estrogen biosynthesis (e.g., aromatase function) in women. Research from Chen’s and other laboratories have revealed that estrogen receptors (ER), aromatase, and ERR are key players in breast cancer promotion and in cancer recurrence following endocrine treatment. Furthermore, proof-of-concept studies have revealed that these proteins are targets of endocrine disruptors. Based on these observations, we hypothesize that environmental chemicals will play critical roles in modulating breast cancer through ER, aromatase and ERR. We have developed a high throughput screening system (AroER Tri-Screen™) for identifying chemicals targeting ER and aromatase. The goal of this research is to develop screening assays for identifying and testing chemicals with relevance to known and suspected causes of estrogen-dependent breast cancer. Our collaborators include Yate-Ching Yuan, Ph.D. (Bioinformatics Core), Xiwei Wu, M.D., Ph.D. (Integrative Genomics Core), Christina Teng, Ph.D. (National Institute of Environmental Health Sciences), Menghang Xia, Ph.D., and Ruiling Huang, Ph.D. (National Center for Advancing Translational Sciences), Sandra Finestone, Psy.D. (Hope Wellness Center, Costa Mesa, California) and Kimlin Tam Ashing, Ph.D. (Population Sciences). Furthermore, we are collaborating with Myrto Petreas, Ph.D. (California Department of Toxic Substances Control) and Peggy Reynolds, Ph.D. (Cancer Prevention Institute of California) for the evaluation of estrogenic activity in human serum using AroER Tri-Screen.

Lauren Bernal, B.S.
Research Associate I
626-218-5062

Gregory Chang, Ph.D.
Research Associate I
626-218-5061

Hang-Kai Hsu, Ph.D.
Research Associate II
626-218-5062

Pei-Yin Hsu, Ph.D.
Post-doctoral Fellow
626-218-5061

Noriko Kanaya, PhD
Staff Scientist
626-218-5062

Karineh Petrossian, Ph.D.
Post-doctoral Fellow
626-218-5062

Yuan-Zhong Wang, Ph.D.
Staff Scientist
626-218-5062

Takuro Yamamoto, Ph.D.
Post-doctoral Fellow
626-218-5062
 
 
 
 

 

Selected Peer-reviewed Publications (Selected from 243 peer-reviewed publications)

Wang Y, Zhou D, Phung S, Warden C, Rashid R, Chan N, Chen S. SGK3 sustains ERα signaling and drives acquired aromatase inhibitor resistance through maintaining endoplasmic reticulum homeostasis. Proc Natl Acad Sci USA, in press, 2017. PMID: 28174265

Kanaya N, Somlo G, Wu J, Frankel P, Kai M, Liu X, Wu S, Nguyen D, Chan N, Hsieh MY, Kirschenbaum M, Kruper L, Vito C, Badie B, Yim JH, Yuan Y, Hurria A, Peiguo C, Mortimer J, Chen S. Characterization of patient-derived tumor xenografts (PDXs) as models for estrogen receptor positive (ER+HER2- and ER+HER2+) breast cancers. J Steroid Biochem Mol Biol., in press, 2016. PMCID: PMC5094906
 
Mu Y, Li X, Wang Y, Chen S, Liu JP. A systematic review of randomized controlled trials on oral Chinese herbal medicine for prostate cancer. PLoS One, 11: e0160253, 2016. PMCID: PMC4973922
 
Chen Z, Wang O, Nie M, Elison K, Zhou D, Li M, Jiang Y, Xia W, Meng X, Chen S, Xing X. Aromatase deficiency in a Chinese adult man caused by novel compound heterozygous CYP19A1 mutations: effects of estrogen replacement therapy on the bone, lipid, liver and glucose metabolism. Mol Cell Endocrinol. 399: 32-42, 2015. PMCID: PMC4457386
 
Chen Z, Wang Y, Warden C, Chen S. Cross-talk between ER and HER2 regulates c-MYCmediated glutamine metabolism in aromatase inhibitor resistant breast cancer cells. J Steroid Biochem Mol Biol, 149: 118-27, 2015. PMCID: PMC4380584
 
Twardowski P, Kanaya N, Frankel P, Synold T, Ruel C, Pal SK, Junqueira M, Prajapati M, Nguyen T, Tryon P, Chen S. A phase I trial of mushroom powder in patients with biochemically recurrent prostate cancer: roles of cytokines and myeloid-derived suppressor cells (MDSCs) for Agaricus bisporus induced PSA responses, Cancer, 121: 2942-50, 2015. PMID: 25989179
 
Kai M, Kanaya N, Wu S, Mendez C, Nguyen D, Luu T, Chen S. Targeting breast cancer stem cells in triple negative breast cancer using a bombination of LBH589 and salinomycin. Breast Cancer Research & Treatment, 151: 281-94, 2015. PMCID:PMC4587767
 
Kanaya N, Nguyen DM, Lu H, Wang YZ, Hsin LY, Petreas M, Nelson D, Guo W, Reynolds P, Synold T, and Chen S. AroER tri-screen™ is a novel functional assay to estimate both estrogenic and estrogen precursor activity of chemicals or biological specimens. Breast Cancer Research & Treatment, 151: 335-45, 2015. PMCID:PMC4591046
 
Wu VS, Kanaya N, Lo C, Mortimer J, Chen S. From bench to bedside: What do we know about hormone receptor-positive and human epidermal growth factor receptor 2-positive breast cancer? J Steroid Biochem Mol Biol, 153: 45-53, 2015. PMCID:PMC4568143
 
Chen Z, Yuan YC, Wang Y, Liu Z, Chan HJ, Chen S. Down-regulation of programmed cell death 4 (PDCD4) is associated with aromatase inhibitor resistance and a poor prognosis in estrogen receptor-positive breast cancer. Breast Cancer Res Treat, 152: 29-39, 2015. PMCID: PMC4470793
 
Chen S, Hsieh JH, Huang R, Sakamuru S, Hsin LY, Xia M, Shockley KR, Auerbach S, Kanaya N, Lu H, Svoboda D, Witt KL, Merrick BA, Teng CT, Tice RR. Cell-based highthroughput screening for aromatase inhibitors in the Tox 21 10K library. Toxicol Sci, 147: 446-57, 2015. PMCID: PMC4592355
 
Chan HJ, Li H, Liu Z, Yuan YC, Mortimer J, Chen S. SERPINA1 is a direct estrogen receptor target gene and a predictor of survival in breast cancer patients. Oncotarget, 6: 25815-27, 2015. PMCID: PMC4694868
 
Wang YZ, Xu W, Zhou D, Neckers L, Chen S. Coordinated regulation of Serum- and GlucocorticoidInducible Kinase 3 by a C-terminal hydrophobic motif and Hsp90-Cdc37 chaperone complex. J Biol Chem, 289: 4815-26, 2014. PMCID: PMC3931044
 
Chen S, Zhou D, Hsin LY, Kanaya N, Wong C, Yip R, Sakamuru S, Xia M, Yuan YC, Witt K, Teng C. AroER tri-screen™ is a biologically relevant assay for endocrine disrupting chemicals modulating the activity of aromatase and/or the estrogen receptor. Toxicological Sciences, 139: 198-209, 2014. PMCID: PMC4038786
 
Wang Y, Wong TY, Chan FL, Chen S, Leung LK. Assessing the effect of food mycotoxins on aromatase by using a cell-based system. Toxicol In Vitro, 28: 640-6, 2014. PMID: 24512813
 
Wang Y, Zhou D, Chen S. SGK3 is an androgen-inducible kinase promoting prostate cancer
cells proliferation trough activation of p70 S6 kinase and up-regulation of cyclin D1. Mol
Endocrinol, 28: 935-948, 2014. PMCID: PMC4042072
 
Wong TY, Li F, Lin SM, Chan FL, Chen S, Leung LK. Celecoxib increases miR-222 while
deterring aromatase-expressing breast tumor growth in mice. BMC Cancer, 14: 426, 2014
PMCID: PMC4070644
 
Li F, Wong TY, Lin SM, Chow S, Cheung WH, Chan FL, Chen S, Leung LK.
Coadministrating luteolin minimizes the side effects of the aromatase inhibitor letrozole. J
Pharmacol Exp Ther, 351: 270-7, 2014 PMID: 25138022
 
Kubo M, Kanaya N, Petrossian K, Ye J, Warden C, Liu Z, Nishimura R, Osako T, Okido M,
Shimada K, Takahashi M, Chu P, Yuan YC, Chen S. Inhibition of the proliferation of
acquired aromatase inhibitor-resistant breast cancer cells by histone deacetylase inhibitor
LBH589 (panobinostat). Breast Cancer Res Treat, 137: 93-107, 2013. PMCID:
PMC3637924
 
Li F, Chow S, Cheung WH, Chan FL, Chen S, Leung LK. The citrus flavonone hesperetin
prevents letrozole-induced bone loss in a mouse model of breast cancer. J Nutr Biochem, 24:
1112-6, 2013. PMID: 23238426
 
Kanaya N, Vonderfecht S, Chen S, Androgren (dihydrotestosterone)-mediated regulation of
food intake and obesity in female mice. J Steroid Biochem Mol Biol, 138: 100-6, 2013.
PMID: 23665441
 
Warden CD, Kanaya N, Chen S, Yuan YC. BD-Func: a streamlined algorithm for predicting
activation and inhibition of pathways. PeerJ, 1: e159, 2013. PMCID: PMC3775632
 
Kanaya N, Adams L, Takasaki A, Chen S. Whole blueberry powder inhibits metastasis of
triple negative breast cancer in a xenograft mous model through modulation of inflammatory
cytokines. Nutr Cancer, 66: 242-8, 2013. PMID: 24364759
 
  • 2016, Ad hoc reviewer for the BMCT Study Section, NIH
  • 2016, Ad hoc reviewer for the Molecular and Cellular Endocrinology Study Section, NIH
  • 2010, Member of the Breast Cancer and the Environment Study Section, NIEHS
  • 2008-2012, Member of the Molecular and Cellular Endocrinology Study Section, NIH
  • 2006, Programmatic review for the DOD Breast Cancer Research Program
  • 2006, Reviewer for applications for the Tumor Microenvironment Network, NIH
  • 2006 - present, Section Editor, Journal of Molecular Signaling
  • 2006, Reviewer for the Mouse Metabolic Phenotyping Centers Consortium, NIH
  • 2004, Reviewer for the botanical center grant applications, NIH
  • 2003-2005, Member of the Tumor Cell Biology Study Section, NIH
  • 2002-2003, Member of the Metabolic Pathology Study Section, NIH
  • 2002-Present, Corresponding Editor, The Journal of Steroid Biochemistry and Molecular Biology
  • 2002, Reviewer for the SCOR applications, NIH
  • 2000-Present, Member of Special Emphasis Panels, NIH
  • 2000-2001, Chairman of the Student Research Committee, American Heart Association, Western States Affiliate
  • 1999-2000, Member of the Study Section for Insight Award for Breast Cancer, NIH
  • 1998-1999, U.S. Environmental Protection Agency, Endoctrine Disruptor Study Section
  • 1998-2002, Member of the Research Committee, American Heart Association, Western States Affiliate
  • 1996-1998, 2001-2003, 2005, Member of the Study Sections of the US Army Breast Cancer Research Program
  • 1996-2000, Member of the Reproductive Endocrinology Study Section, NIH
  • 1985-Present, Member of the City of Hope Cancer Center
Back To Top