實驗室安全及衛生公告
About the EMPreSS Lab
Welcome to the EMPreSS Lab！
EMPreSS (Epithelial Mesenchymal Precision Spectrum Scoring) is a new system to assess the epithelial and mesenchymal states from the concept of a spectrum beyond the traditional binary perspective.
Our fundamental questions are:
- What makes the epithelial, epithelial?
- What is the precise estimation of “mesenchymality”?
- What is the fluidity of the interchange among different states?
Epithelial-Mesenchymal Transition (EMT)
Epithelial-mesenchymal transition (EMT), an evolutionary conserved mechanism during development, is a reversible and dynamic process proposed to be co-opted by carcinoma during disease progression and therapeutic refractoriness. The concept of EMT has evolved from a binary phenomenon of epithelial (E) and mesenchymal (M) states to a continuous spectrum, which includes intermediate hybrid E/M states. The fluidity to transit in between different states is referred as the epithelial-mesenchymal plasticity (EMP). This EMP along the continuous spectrum reflects the transition through multiple barriers which is similar to the concept of metastability. The barriers of EMP include the transcriptional regulatory network (GRN) among several transcription factors (TFs) such as SNAI1, SNAI2, ZEB1, ZEB1, TWIST1, and the epithelial transcriptional gatekeepers, such as GRHL2 and OVOL2. For successful transitions in between states, different repertoires of transcriptional networks and epigenetic regulations need to be precisely orchestrated.
◎ Heterogeneity of EMT
Acknowledging the existence of EMT as a spectrum, solving the heterogeneity of EMT thus becomes an inevitable task. Our lab takes several approaches to dissect the heterogeneity of EMT from multiple dimensions: (1) the fluidity of transition; (2) the genome architecture; (3) the spatial context.
(1) Fluidity of state transitions
We hypothesize that overcoming different barriers in between states is required for transition. The reversibility and plasticity depends on introducing the correct regulatory network permissive for fluidity at that given state along the spectrum.
To test the hypothesis, we adopt several different systems to drive the transition plasiticty using a panel of cancer cell lines which have been phenotypically characterized along the EMT Spectrum.
- 4-cell-line EMT phenotypic spectrum model
- TF-driven model
(2) 3D genome architecture during state transitions
The transcriptional control of EMT by a network of transcription factors (TFs) (eg. SNAI1, SNAI2, ZEB1, ZEB1, TWIST1, GRHL2, and OVOL2) has been demonsrated extensively. In order to achieve efficient state transitions, the genome needs to adapt accordingly. Looking at the genome adaptation from the 3-dimensional (3D) perspective, we adopt several techniques including chromosome conformation capture to address this aspect.
- Chromatin accessibility
- 3D genome structure
(3) Spatial heterogeneity of EMT
The contribution from the microenvironment matters tremendously on how EMT is executed, especially during carcinoma progression. The heterogeneity of EMT is best examplified by the leading cells or cell clusters located at the "invasive front" of a solid tumor versus the tumor bulk. We apply the state-of-the-are technoloy platform of Digital Spatial Profiling (DSP) to dissect the EMT heterogeneity within the spatial context.
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Ovarian Cancer (OC)
Ovarian cancer (OC) is a heterogeneous disease entity. The heterogeneity is reflected in several aspects including genetic susceptability, tumorigenesis mechanism, histological differentiation, and multi-omics profiles. Our lab utilizes OC as a disease model to develop pre-clinical, translational, and clinical R&D pipelines to achieve precision medicine. We focus on specific subtypes of OC and explore their unique biology.
◎ Ovarian clear cell carcinoma (OCCC)
Ovarian clear cell carcinoma (OCCC) is a histological subtype with distinct pathological features, molecular profiles, and biological functions. OCCCs are more resistant to conventional treatment regimen and have the worst stage-adjusted prognosis amongst OC subtypes. As the OCCC incidence rate in Asian populations rising in recent decades, there is thus an urgent need to identify more effective treatments to improve outcomes for patients. Currently, there is a significant gap in addressing the heterogeneity of OCCC and an unmet need to develop comprehensive research platforms for pre-clinical, translational, and clinical purposes. Several investigators in National Taiwan University have thus joined force to form a research consortium.
◎ National Taiwan University (NTU) OCCC Core Consortium
◆Main Project Title
Dissecting the Molecular, Functional, and Therapeutic Heterogeneity of Ovarian Clear Cell Carcinoma
◆Overall Aim:
To address the heterogeneity within OCCC by establishing various research platforms which could lead to future translational applications for biomarkers and novel therapeutic discoveries.
◆Sub-projects:
◦ Professor Ruby Huang, School of Medicine (Lead PI)
Assessing the molecular heterogeneity of OCCC in the chorioallantoic membrane (CAM) xenograft model
◦ Assistant Professor Feng-Chiao Tsai, Department of Pharmacology (PI)
Investigating migratory aggressiveness of OCCC via Ca2+adhesion interactions
◦ Professor Ling-Hung Wei, Department of Obstetrics & Gynecology (PI)
Targeting IL-6/gp130/STAT3 Signaling in Ovarian Clear Cell Carcinoma: Strategic Research on Target Identification
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Chorioallantoic Membrane-xenograft (CAM-X) assay
The CAM assay is an in vivo animal model that involves the implantation of tumor cells or patient-derived tissues on the extra-embryonic membrane or CAM of the developing chick embryo. Our lab utilizes CAM as a model xenograft to mimic growth of tumor cells in animal body and hence investigate in the impact of EMT induction in vivo. The tumor growth will be assessed by the serial ultrasound imaging measurement to determine the change in tumor volume over time. The metastatic ability will be evaluated by detecting human specific Alu sequences through PCR from the chick embryos organs and histological studies of the tumor grafts.
◎ CAM workflow
Tumor graft implanted on the surface of CAM would be harvested on ED14 and subsequently fixed with formalin for H&E staining. The tumor cell morphology is observed under microscope.
EMPreSS Highlight