As the Scientific Director of RNA Medicine Program at Stanford University, Dr. Miao-Chih Tsai leads and manages research portfolio of RNA Medicine Program. Before this role, she was a senior editor of Cell. Dr. Tsai was trained as a scientist at University of Cambridge and Stanford University, and had over a decade of experience in evaluating the top developments in biomedical research. Having experienced its power to inspire, she is an ardent proponent of science and strives to directly promote further advancements and shape the direction of biomedical research, with a goal of therapeutic application and patient impact.
Honors & Awards
Corpus Christi College Research Scholarship, University of Cambridge (2002-2006)
University of Cambridge Overseas Trust Scholarship, University of Cambridge (2002-2006)
Dean's Fellowship, Stanford University (2008-2009)
Postdoctoral fellowship, Taiwan National Science Foundation (2009)
Postdoctoral Fellowship, Susan G, Komen (2009-2012)
Education & Certifications
Ph.D., University of Cambridge, Genetics (2006)
M.Sc, National Taiwan University (2000)
Long Intergenic Noncoding RNAs: New Links in Cancer Progression
2011; 71 (1): 3-7
The process of cancer metastasis involves a series of sequential and complex steps. Here we give a perspective on recent results regarding noncoding transcription in cancer progression, focusing on the emerging role of long intergenic noncoding RNAs (lincRNAs). LincRNAs target chromatin modification complexes or RNA-binding proteins to alter gene expression programs. Similarly to miRNAs, lincRNAs exhibit distinct gene expression patterns in primary tumors and metastases. We discuss how lincRNAs can be used for cancer diagnosis and prognosis and serve as potential therapeutic targets.
View details for DOI 10.1158/0008-5472.CAN-10-2483
View details for PubMedID 21199792
Long Noncoding RNA as Modular Scaffold of Histone Modification Complexes
2010; 329 (5992): 689-693
Long intergenic noncoding RNAs (lincRNAs) regulate chromatin states and epigenetic inheritance. Here, we show that the lincRNA HOTAIR serves as a scaffold for at least two distinct histone modification complexes. A 5' domain of HOTAIR binds polycomb repressive complex 2 (PRC2), whereas a 3' domain of HOTAIR binds the LSD1/CoREST/REST complex. The ability to tether two distinct complexes enables RNA-mediated assembly of PRC2 and LSD1 and coordinates targeting of PRC2 and LSD1 to chromatin for coupled histone H3 lysine 27 methylation and lysine 4 demethylation. Our results suggest that lincRNAs may serve as scaffolds by providing binding surfaces to assemble select histone modification enzymes, thereby specifying the pattern of histone modifications on target genes.
View details for DOI 10.1126/science.1192002
View details for PubMedID 20616235
- Tumor suppression by the histone demethylase UTX CELL CYCLE 2010; 9 (11): 2043-2044
Long non-coding RNA HOTAIR reprograms chromatin state to promote cancer metastasis
2010; 464 (7291): 1071-U148
Large intervening non-coding RNAs (lincRNAs) are pervasively transcribed in the genome yet their potential involvement in human disease is not well understood. Recent studies of dosage compensation, imprinting, and homeotic gene expression suggest that individual lincRNAs can function as the interface between DNA and specific chromatin remodelling activities. Here we show that lincRNAs in the HOX loci become systematically dysregulated during breast cancer progression. The lincRNA termed HOTAIR is increased in expression in primary breast tumours and metastases, and HOTAIR expression level in primary tumours is a powerful predictor of eventual metastasis and death. Enforced expression of HOTAIR in epithelial cancer cells induced genome-wide re-targeting of Polycomb repressive complex 2 (PRC2) to an occupancy pattern more resembling embryonic fibroblasts, leading to altered histone H3 lysine 27 methylation, gene expression, and increased cancer invasiveness and metastasis in a manner dependent on PRC2. Conversely, loss of HOTAIR can inhibit cancer invasiveness, particularly in cells that possess excessive PRC2 activity. These findings indicate that lincRNAs have active roles in modulating the cancer epigenome and may be important targets for cancer diagnosis and therapy.
View details for DOI 10.1038/nature08975
View details for Web of Science ID 000276635000045
View details for PubMedID 20393566
View details for PubMedCentralID PMC3049919
The histone demethylase UTX enables RB-dependent cell fate control
GENES & DEVELOPMENT
2010; 24 (4): 327-332
Trimethylation of histone H3 on Lys 27 (H3K27me3) is key for cell fate regulation. The H3K27me3 demethylase UTX functions in development and tumor suppression with undefined mechanisms. Here, genome-wide chromatin occupancy analysis of UTX and associated histone modifications reveals distinct classes of UTX target genes, including genes encoding Retinoblastoma (RB)-binding proteins. UTX removes H3K27me3 and maintains expression of several RB-binding proteins, enabling cell cycle arrest. Genetic interactions in mammalian cells and Caenorhabditis elegans show that UTX regulates cell fates via RB-dependent pathways. Thus, UTX defines an evolutionarily conserved mechanism to enable coordinate transcription of a RB network in cell fate control.
View details for DOI 10.1101/gad.1882610
View details for PubMedID 20123895
Microtubules are involved in anterior-posterior axis formation in C-elegans embryos
JOURNAL OF CELL BIOLOGY
2007; 179 (3): 397-402
Microtubules deliver positional signals and are required for establishing polarity in many different organisms and cell types. In Caenorhabditis elegans embryos, posterior polarity is induced by an unknown centrosome-dependent signal. Whether microtubules are involved in this signaling process has been the subject of controversy. Although early studies supported such an involvement (O'Connell, K.F., K.N. Maxwell, and J.G. White. 2000. Dev. Biol. 222:55-70; Wallenfang, M.R., and G. Seydoux. 2000. Nature. 408:89-92; Hamill, D.R., A.F. Severson, J.C. Carter, and B. Bowerman. 2002. Dev. Cell. 3:673-684), recent work involving RNA interference knockdown of tubulin led to the conclusion that centrosomes induce polarity independently of microtubules (Cowan, C.R., and A.A. Hyman. 2004. Nature. 431:92-96; Sonneville, R., and P. Gonczy. 2004. Development. 131: 3527-3543). In this study, we investigate the consequences of tubulin knockdown on polarity signaling. We find that tubulin depletion delays polarity induction relative to wild type and that polarity only occurs when a small, late-growing microtubule aster is visible at the centrosome. We also show that the process of a normal meiosis produces a microtubule-dependent polarity signal and that the relative levels of anterior and posterior PAR (partitioning defective) polarity proteins influence the response to polarity signaling. Our results support a role for microtubules in the induction of embryonic polarity in C. elegans.
View details for Web of Science ID 000250705200007
View details for PubMedID 17967950
The C-elegans hook protein, ZYG-12, mediates the essential attachment between the centrosome and nucleus
2003; 115 (7): 825-836
The centrosome and nucleus are intimately associated in most animal cells, yet the significance of this interaction is unknown. Mutations in the zyg-12 gene of Caenorhabditis elegans perturb the attachment of the centrosome to the nucleus, giving rise to aberrant spindles and ultimately, DNA segregation defects and lethality. These phenotypes indicate that the attachment is essential. ZYG-12 is a member of the Hook family of cytoskeletal linker proteins and localizes to both the nuclear envelope (via SUN-1) and centrosomes. ZYG-12 is able to bind the dynein subunit DLI-1 in a two-hybrid assay and is required for dynein localization to the nuclear envelope. Loss of dynein function causes a low percentage of defective centrosome/nuclei interactions in both Drosophila and Caenorhabditis elegans. We propose that dynein and ZYG-12 move the centrosomes toward the nucleus, followed by a ZYG-12/SUN-1-dependent anchorage.
View details for Web of Science ID 000187664700007
View details for PubMedID 14697201
TAC-1, a regulator of microtubule length in the C-elegans embryo
2003; 13 (17): 1499-1505
Regulation of microtubule growth is critical for many cellular processes, including meiosis, mitosis, and nuclear migration. We carried out a genome-wide RNAi screen in Caenorhabditis elegans to identify genes required for pronuclear migration, one of the first events in embryogenesis requiring microtubules. Among these, we identified and characterized tac-1 a new member of the TACC (Transforming Acidic Coiled-Coil) family . tac-1(RNAi) embryos exhibit very short microtubules nucleated from the centrosomes as well as short spindles. TAC-1 is initially enriched at the meiotic spindle poles and is later recruited to the sperm centrosome. TAC-1 localization at the centrosomes is regulated during the cell cycle, with high levels during mitosis and a reduction during interphase, and is dependent on aurora kinase 1 (AIR-1), a protein involved in centrosome maturation. tac-1(RNAi) embryos resemble mutants of zyg-9, which encodes a previously characterized centrosomal protein of the XMAP215 family and was also found in our screen. We show that TAC-1 and ZYG-9 are dependent on one another for their localization at the centrosome, and this dependence suggests that they may function together as a complex. We conclude that TAC-1 is a major regulator of microtubule length in the C. elegans embryo.
View details for DOI 10.1016/S0960-9822(03)00577-3
View details for Web of Science ID 000185171300019
View details for PubMedID 12956951
C-elegans CED-12 acts in the conserved CrkII/DOCK180/Rac pathway to control cell migration and cell corpse engulfment
2001; 1 (4): 491-502
We have identified and characterized a novel C. elegans gene, ced-12, that functions in the conserved GTPase signaling pathway mediated by CED-2/Crkll, CED-5/DOCK180, and CED-10/Rac to control cell migration and phagocytosis of apoptotic cells. We provide evidence that ced-12 likely acts upstream of ced-10 during cell migration and phagocytosis and that CED-12 physically interacts with CED-5 and forms a ternary complex with CED-2 in vitro. We propose that the formation and localization of a CED-2-CED-5-CED-12 ternary complex to the plasma membrane activates CED-10, leading to the cytoskeletal reorganization that occurs in the polarized extension of cell surfaces in engulfing cells and migrating cells. We suggest that CED-12 counterparts in higher organisms regulate cytoskeleton dynamics, as CED-12 does in C. elegans.
View details for Web of Science ID 000175301500009
View details for PubMedID 11703940