Liye Zhang, Ph.D.
Postdoctoral Fellow, Monti Lab
2007 B.S. Biotechnology, Shanghai Jiaotong University, Shanghai, China
2012 Ph.D. Cell and Developmental Biology, Penn State University, State College, PA
Project Title : Pan-cancer Study of the role of RNA editing
RNA editing is a molecular event that alters specific nucleotides in RNA post-transcriptionally. RNA editing has the potential to impact a variety of cellular processes and is implicated in diseases such as cancer. We characterize sequences altered by RNA editing in patient samples from lymphoma, neuroblastoma and head and neck cancers. We show that A-to-I RNA editing sites are highly conserved across samples of the same tissue type and that most editing sites identified in tumors are also detectable in normal tissues. We also identify the significant changes in editing levels of known sites between tumor and paired “normal” tissues across 14 cancer types (627 pairs) from The Cancer Genome Atlas project and show that the complexity of RNA editing regulation cannot be captured by the activity of ADAR family genes alone. Our pan-cancer analysis confirms previous results on individual tumor types and suggests that changes of RNA editing levels in coding and 3′UTR regions could be a general mechanism to promote tumor growth. We also propose a model explaining how altered RNA editing levels affect microRNA-mediated post-transcriptional regulation of oncogenes and tumor-suppressors. [press release]
Project Title : Mechanisms of ALK mediated metastasis in lung cancer
Anaplastic Lymphoma Kinase (ALK) is a key oncogene in multiple cancers. We discovered that ALK also plays important roles in metastasis in lung cancer. To elucidate its mechanism of action, lung cell lines were treated with pharmacologic and molecular (siRNA) ALK inhibitors, and their transcriptional response was profiled by RNA-Seq. The differentially expressed genes upon ALK inhibition were significantly enriched for Epithelial-Mesenchymal Transition (EMT) genes, thus supporting ALK’s role in metastasis. We also found that multiple epithelial specific isoforms (such as CD44e) were regulated by ALK. We then developed an algorithm to predict the key splicing factor by RNA-Seq alone and identified the epithelial-specific splicing factors ESRP1/2, through which ALK regulates multiple epithelial-related splicing isoforms. Interestingly, we found that E-cadherin expression is also repressed by ALK through ESRP1/2. To further characterize the key downstream pathway of ALK signaling in regulating metastasis, we performed mass-spectrometry experiments to characterize global phosphorylation changes upon ALK inhibition and identified ERK pathway in lung cancer. In summary, we showed that ALK regulates EMT gene expression and specific isoforms through ESRP1/2 and ERK signaling pathway.
Project Title: The role of TAZ/YAP in tumorigenesis
The TAZ/YAP pathway plays a crucial role in multiple tumor types. In this study, we apply diverse computational methods to elucidate the mechanisms of TAZ/YAP-driven tumorigenesis in different cancer types. We also study the interaction between TAZ/YAP and epigenetic regulators, such as microRNAs, and the role of such interaction in tumor progression in cancer cell lines and mouse models.
- Claudia Voena#, Lydia Varesio#, Liye Zhang#, Matteo Menotti, Teresa Poggio, Elena Panizza, Qi Wang, Valerio Minero, Shamila Fagonee, Mara Compagno, Fiorella Altruda, Stefano Monti, Roberto Chiarle. Oncogenic ALK regulates EMT in Non-Small Cell Lung Carcinoma through repression of the epithelial splicing regulatory protein 1. Oncotarget 2016 Apr 23. doi: 10.18632/oncotarget.8955
- Liye Zhang*, Chih-Cheng Yang, Xaralabos Varelas, Stefano Monti*. Altered A-to-I RNA editing in 3’ UTR perturbs microRNA-mediated regulation of oncogenes and tumor suppressor genes. Scientific Reports 2016 Mar 16; 6:23226
- Takuma Suematsu#, Liye Zhang#, Inna Aphasizheva, Stefano Monti, Lan Huang, Catherine Costello, Ruslan Aphasizhev. Antisense Transcripts Impede Uridylation-induced Exonucleolytic Degradation to Generate Guide RNAs. Molecular Cell 2016 Feb 4; 61(3): 364-378
- Inna Aphasizheva#, Liye Zhang#, Xiaorong Wang, Robyn Kaake, Lan Huang, Stefano Monti and Ruslan Aphasizhev. RNA binding and core complexes constitute the u-insertion/deletion editosome. Molecular and Cellular Biology 2014 Dec 1; 34(23): 4329-42
- Liye Zhang, Hong Ma, Frank Pugh. Stable and dynamic nucleosome states during a meiotic developmental process. Genome Research 2011 Jun; 21(6): 875-884.
- Bjoern Chapuy, Margaretha Roemer, Chip Stewart, Yuxiang Tan, Ryan Abo, Liye Zhang, Andrew Dunford, David Meredith, Aaron Thorner, Ekaterina Jordanova, Gang Liu, Friedrich Feuerhake, Matthew Ducar, Gerald Illerhaus, Daniel Gusenleitner, Erica Linden, Heather Sun, Heather Homer, Miyuki Aono, Geraldine Pinkus, Azra Ligon, Keith Ligon Judith Ferry, Gordon Freeman, Paul Hummelen, Todd Golub, Gad Getz, Scott Rodig, Daphne Jong, Stefano Monti, Margaret Shipp. Targetable genetic features of primary testicular and primary central nervous system lymphomas. Blood 2016 Feb 18;127(7):869-881
- Bjoern Chapuy, Hongwei Cheng, Akira Watahiki, Matthew Ducar, Daniel Gusenleitner, Linfeng Chen, Margaretha Roemer, Jing Quyang, Amanda Christie, Liye Zhang, Yuxiang Tan, Ryan Abo, Frederike Bonin, Aaron Thorner, Heather Sun, Geraldine Pinkus, Paul van Hummelen, Gerald Wulf, Jon Aster, David Weinstock, Stefano Monti, Scott Rodig, Yuzhuo Wang, Margaret Shipp. Diffuse Large B-cell Lymphoma Patient-derived Xenograft Models Capture the Molecular and Biologic Heterogeneity of the Disease. (E-published in Blood)
- Samantha Hiemer, Liye Zhang, Vinay Kartha, Munirah Almershed, Stefano Monti, Maria Kukuruzinska, Xaralabos Varelas. A YAP/TAZ-regulated transcriptional signature associated with Oral Squamous Cell Carcinoma. Molecular Cancer Research. 2015 Jun; 13(6): 957-968
- Ho Sung Rhee, Alain R. Bataille, Liye Zhang, Benjamin F Pugh. Subnucleosomal Structures and Nucleosome Asymmetry Across a Genome. Cell 2014 Dec 4; 159(6): 1377-1388
- Jessica M. Bryant, Jérome Govin, Liye Zhang, Gregory Donahue, B. Franklin Pugh, Shelley L. Berger. The linker histone plays a dual role during gametogenesis in S. cerevisiae. Molecular and Cellular Biology 2012 Jul; 32(14): 2771-83