Dr Ruby Yun-Ju Huang was trained as a gynaecological oncologist in Taiwan, but has made the unusual step of pursuing a career as a Clinician Scientist. She has long-standing interest in epithelial-mesenchymal transition (EMT) which was the focus of her PhD, establishing the link between the responsiveness to growth factor-induced colony dispersal and epithelial and mesenchymal phenotypes in ovarian cancer cells. She co-discovered the presence of five molecular subtypes in epithelial ovarian cancer that exhibit different epithelial, mesenchymal, and stem cell-like characteristics. The overall aim of her research is to develop novel therapeutics for ovarian cancer through a better understanding of the specific driving mechanisms for each molecular subtype. To do this she has established an ovarian cancer research pipeline including preclinical discovery and translational phases incorporating novel preclinical models (cell lines, PDXs) and large scale genomics data with close collaboration with her clinical colleagues.
Epithelial ovarian cancer (OC) in particular high grade serous carcinoma (HGSC), has been shown to exhibit diverse molecular heterogeneity based on gene expression profiling by the Australian and the TCGA cohorts (Tothill et al., 2008; TCGA, 2011). This molecular heterogeneity has been demonstrated to be very robust and reproducible by a large-scale meta-analysis study consisting of 1,538 samples from our group (Tan, Miow & Huang et al., 2013). At least 5 distinct gene-expression based molecular subtypes (GEMS) of OC have been identified. Among these GEMS, the C5 subtype from the Tothill dataset corresponds to the Proliferative subtype from the TCGA dataset and the Stem-A subtype from the 1,538 meta-analysis dataset. The C1 subtype corresponds to the Mesenchymal and the Mes subtype, the C2 subtype corresponds to the Immunoreactive and the Epi-B subtype, respectively. These GEMS have been correlated with patient survival. In addition to the GEMS, the developmentally crucial mechanism Epithelial-Mesenchymal Transition (EMT) also contributes to the aggressiveness and the molecular heterogeneity of OC (Tan et al., 2014). The C1/Mesenchymal/Mes and C5/Proliferative/Stem-A GEMS is associated with poorer survival outcomes and high EMT scores; while the C3/Differentiated/Epi-A, C4/Differentiated/Epi-B, and C2/Immunoreactive/Epi-B show good prognosis and are associated with low EMT scores. In addition to prognostication, these GEMS and the associated EMT states may also be relevant to therapeutic stratification.
The vision of the OC research group is to set up a translational program aiming at molecular subtype specific stratification for OC patients. The specific aims are to establish an operational workflow for molecular subtype diagnosis in OC; to establish pre-clinical pipelines for novel therapeutics for OC molecular subtypes utilizing characterized OC cell lines and patient-derived xenografts (PDXs); to decipher the biology of the driving mechanisms for OC molecular subtypes.
- Chung VY, Wong MK, Kuay KT, Tan TZ, Guccione E, Thiery JP*, and Huang RY*. GRHL2-miR-200-ZEB1 maintains the epithelial status of ovarian cancer through transcriptional regulation and histone modification. Scientific Reports 2016 6, 19943 * Co-senior author.
- Tan TZ, Yang H, Ye J, Low J, Choolani M, Tan D, Thiery JP, Huang RY. CSIOVDB: a microarray gene expression database of epithelial ovarian cancer subtype. 2015 6(41):43843-52.
- Huang RY, Kuay KT, Tan TZ, Asad M, Tang HM, Ng AH, Ye J, Chung VY, and Thiery JP. Functional Relevance of a Six Mesenchymal Gene Signature in Epithelial-Mesenchymal Transition (EMT) Reversal by the Triple Angiokinase Inhibitor, Nintedanib (BIBF1120). Oncotarget. 2015 6(26):22098-113.
- Tan TZ, Miow QH, Miki Y, Matsuura M, Noda T, Mori S, Huang RY*, and Thiery JP*. Epithelial‐mesenchymal transition (EMT) spectrum quantification and its efficacy in deciphering survival and drug responses of cancer patients. EMBO Mol Med 2014 e201404208 * Co-senior author.
- Asad M, Wong MK, Tan TZ, Choolani M, Low J, Mori S, Virshup D, Thiery JP, and Huang RY. FZD7 drives aggressiveness in Stem-A subtype of ovarian cancer via regulation of non-canonical Wnt/PCP pathway. Cell Death & Disease 2014 5, e1346
- Ng A, Tan S, Singh G, Rizk P, Swathi Y, Tan TZ, Huang RY, Leushacke M, and Barker N. Lgr5+ Stem/Progenitor Cells Contribute to the Development and Maintenance of the Ovary and Tubal Epithelia. Nat Cell Biol. 2014 2014 16 (8), 745-757
- Ding LW, Sun QY, Lin DC, Chien W, Hattori N, Dong XM, Gery S, Garg M, Doan N, Said J, Xiao JF, Yang H, Liu LZ, Meng X, Huang RY, Tang K, and Koeffler H. LNK (SH2B3): paradoxical effects in ovarian cancer. Oncogene. 2014 Apr 7. (IF: 8.56)
- Huang RY*, Wong MK, Tan TZ, Kuay KT, Ng HC, Chung YC, Chu YS, Masumura N, Lai HC, Lee YF, Sim WJ, Tsai C, Pietschmann E, Mori S, Low J, Choolani MA, Thiery JP*. An EMT Spectrum defines an anoikis resistant and spheroidogenic Intermediate Mesenchymal state that is sensitive to E-cadherin restoration by a Src-kinase inhibitor, Saracatinib (AZD0530). * Co-corresponding author. Cell Death & Disease 2013 4 (11), e915
- Tan TZ*, Miow QH*, Huang RY*,Wong MK, Ye J, Lau JA, Wu MC, Luqman Hakim Bin Abdul Hadi, Soong R, Choolani MA, Davidson B, Nesland J, Matsumura N, Mandai M, Konishi I, Chang JT, Thiery JP, Mori S. Functional Genomics Identifies Five Distinct Molecular Subtypes with Clinical Relevance and Pathways for Growth Control in Epithelial Ovarian Cancer. * Co-first author. EMBO Mol Med. 2013 Jul;5(7):983-98.
- Huang RY, Guilford P, Thiery JP. Early events in cell adhesion and polarity during epithelial-mesenchymal transition. J Cell Sci. 2012 Oct 1;125(Pt 19):4417-22.
|Name||Ruby Yun-Ju HUANG|
|Affiliations||Principal Investigator, Cancer Science Institute of Singapore, NUS
Senior Resident Physician, Department of Obstetrics & Gynaecology, NUH
Adjunct Assistant Professor, Department of Anatomy, Yong Loo Lin School of Medicine, NUS
|Institute||Degree (if applicable)||Year(s)|
|National Taiwan University||Ph.D.(First-Class Honor)||2008|
|National Taiwan University||M.D||1999|
|•||Physician (non-specialist track), National University Hospital, Singapore||2009 – Present|
|•||Research Fellow, Institute of Molecular and Cell Biology||2007 – 2009|
|•||Visiting Scientist, University of British Columbia||2006 – 2007|
|•||Clinical Fellow, National Taiwan University Hospital||2003 – 2006|
|•||Residency, National Taiwan University Hospital||1999 – 2003|
Tony TAN Tuan Zea
Senior Research Scientist
a. Integrative analysis of molecular subtype.
CHUNG Vin Yee
To study the potential roles of Discoidin Domain Receptor 1 and Grainyhead-like 2 in Epithelial-Mesenchymal Transition in Epithelial Ovarian Cancer.
To study the role of GRHL2 in regulating actin cytoskeleton re-organizaion during cancer induced EMT.
My work is focused on identifying mechanism of regulation and function of Wnt signalling in normal and cancer stem cells. I’m studying the role of a Wnt receptor in Ovarian cancer that drives to their stemness.
Katty KUAY Kuee Theng
To study the reversal of Epithelial-Mesenchymal Transition(EMT) in ovarian cancer cells.
Perusing the role of DNA damage and repair in oncogenesis.
Senior Laboratory Executive
To study the underlying function of TP53 in Epithelial Mesenchymal Transition.
|•||Best Poster Award (Translational Science), 1st
NCIS Annual Meeting (NCAM)
|•||National University Health System (NUHS) Clinician
Scientist Program Award
|•||Aflac-AACR Scholar in Training Award, 101st AACR Annual
|•||Best Oral Presentation Award Pitch for Funds Round, NUHS||2011|
|•||Poster Award Auersperg Symposium on the Etiology of
|•||FIGO / BSP Postdoctoral Research Fellowship, Federation of
International Gynecology and Obstetrics & Bayer Schering
|•||Taiwan Merit Scholarships (TMS) Program, Ministry of
Education of Taiwan and National Taiwan University
|•||Best Resident Award Department of Obstetrics &
Gynecology, National Taiwan University Hospital
|•||Ching-Hsing Medical Foundation Exchange Clerkship