Lab in the News
The Wistar Institute Appoints Bin Tian, Ph.D., as Professor in the Cancer Center and Co-director of the Center for Systems & Computational Biology
PHILADELPHIA — (May, 1, 2020) — The Wistar Institute, an international biomedical research leader in cancer, immunology and infectious diseases, announces the appointment of molecular systems biologist Bin Tian, Ph.D., as professor in the Cancer Center.
The Tian Laboratory
Expression of the genetic code, from DNA to protein, can be regulated at different stages, much of which takes place after RNA is made. The Tian lab studies RNA biology using a variety of approaches including functional genomics, computational biology, and molecular and cellular biology. They have contributed important knowledge on the mechanisms and consequences of alternative polyadenylation (APA) in development and disease.
Yange Cui, Ph.D.
Chuwei Zhong, Ph.D.
Luyang Wang, Ph.D.
Multiple graduate student and postdoctoral positions are available in the Tian lab. Motivated candidates interested in experimental studies, or computational research or both are encouraged to inquire about the positions by contacting Dr. Bin Tian, firstname.lastname@example.org.
In eukaryotes, almost all protein-coding mRNAs and long non-coding RNAs (lncRNAs) transcribed by RNA polymerase II employ cleavage and polyadenylation (CPA) for 3' end maturation. CPA is also coupled with termination of transcription. A gene can have multiple cleavage and polyadenylation sites (PASs), resulting in mRNA isoforms with different coding sequences and/or 3' untranslated regions (3'UTRs), a phenomenon known as alternative cleavage and polyadenylation (APA). The Tian lab is using novel sequencing methods to identify PASs in major model species to understand the evolution of APA. They are also examining APA dynamics in different cells under various pathological and physiological conditions using single cell-based transcriptome data. The long-term goal is to develop an APA code for APA regulation.
The 3'UTR plays regulatory roles in mRNA metabolism, including mRNA decay, translation, and localization. Sequence and structural motifs embedded in 3'UTRs contribute to 3'UTR functions through interactions with their cognate RNA binding proteins (RBPs), microRNAs (miRNAs), or lncRNAs. The Tian lab recently reported widespread translation-independent endoplasmic reticulum association (TiERA) of mRNAs, in which 3’UTRs play an important role. They are now using cell biology and genomic techniques to examine the underlying mechanism of TiERA. In addition, they are analyzing how ER stress regulates 3’UTR-mediated post-transcriptional control.
The Tian lab recently reported widespread transcript shortening in secretory cell differentiation. The phenomenon, named secretion-coupled APA (SCAP), was observed in multiple professional secretory cells. They are now studying SCAP in B cell differentiation to plasma cells, which is critical for humoral immunity. In addition, activation of other immune cells, such as T cells, monocytes, and macrophages, also involves mRNA isoform changes, although the underlying mechanisms are not the same. The Tian lab is examing regulators involved in mRNA isoform changes in different types of immune cells and key effectors involved in immune reponses. They are also pursuing novel therapeutics to modulate immunity via perturbation of mRNA isoform biogenesis and metabolism.
Dysregulation of 3’ end processing has been shown in multiple cancers. The Tian lab is studying certain cancer cells displaying unusal APA isoform profiles that indicate reliance on 3’ end processing activities for cell survival. In addition, they are studying how transcriptional termination is connected with genome intergrity and APA-associated neoantigens in cancer cells. These studies can lead to novel therapeutic modalities for cancer.
Databases and Software
PolyA_DB is a web-based database created by the Tian lab for comprehensive cataloging of pre-mRNA cleavage and polyadenylation (polyA) sites in multiple species. View Here
APAlyzer is a bioinformatics program developed by the Tian lab for the analysis of APA isoform expression changes by using RNA-seq data. View Here
MAAPER is a bioinformatics program co-developed by the Tian lab and the Li lab at Rutgers University for APA isoform expression analysis by using 3’ end-biased RNA-seq data from bulk samples or single cells. View Here
Zheng, D., Cho, H., Wang, W., Rambout, X., Tian, B., Maquat, L. "3'READS + RIP Defines Differential Staufen1 Binding to Alternative 3'UTR Isoforms and Reveals Structures and Sequence Motifs Influencing binding and Polysome Association." RNA. 2020 Nov;26(11):1621-1636. doi: 10.1261/rna.076133.120. Epub 2020 Aug 12.
Cheng, L.C., Zheng, D., Baljinnyam, E., Sun, F., Ogami, K., Yeung, P.L., Hoque, M., Lu, C., Manley, J.L., Tian, B. "Widespread Transcript Shortening Through Alternative Polyadenylation in Secretory Cell Differentiation." Nat Commun. 2020 Jun 23;11(1):3182. doi: 10.1038/s41467-020-16959-2.
Wang, R., Tian, B. “APAlyzer: a bioinformatic package for analysis of alternative polyadenylation isoforms.” Bioinformatics. 2020 Apr 22; pii: btaa266. doi: 10.1093/bioinformatics/btaa266. Epub ahead of print
Wang, R., Zheng, D., Wei, L., Ding, Q., Tian, B. “Regulation of intronic polyadenylation by PCF11 impacts mRNA expression of long genes." Cell Rep. 2019, Mar 5;26(10):2766-2778. doi: 10.1016/j.celrep.2019.02.049.
Chen, S., Wang, R., Zheng, D., Zhang, H., Chang, X., Wang, K., Li, W., Fan, J., Tian, B., Cheng, H. “The mRNA export receptor NXF1 coordinates transcriptional dynamics, alternative polyadenylation and mRNA export.” Mol Cell. 2019 April 4;74:118-131. Doi:10.1016/j.molcel.2019.01.026
Italo Tempera, Ph.D.
Associate Professor, Gene Expression & Regulation Program, The Wistar Institute Cancer Center
Associate Director for Education, The Wistar Institute Cancer Center