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Bin Tian, Ph.D.

Laboratory

The Tian Laboratory

Contact

215-898-3922
btian@wistar.org

Professor and Program Co-Leader, Gene Expression & Regulation Program, The Wistar Institute Cancer Center  

Co-director, Center for Systems & Computational Biology

About the Scientist

Tian is a molecular systems biologist whose research is focused on understanding how gene expression is regulated at the RNA level. His lab was among the first to discover the widespread nature of alternative polyadenylation (APA) using bioinformatic and genomic approaches. They have also revealed multiple molecular mechanisms that regulate APA and cellular functions of APA isoforms in a number of biological systems. 

Tian received his B.S. degree in biochemistry from East China University of Science and Technology and his Ph.D. degree in molecular biology from Rutgers Biomedical and Health Sciences (formerly UMDNJ). He was a postdoctoral fellow in bioinformatics and genomics at Johnson & Johnson Pharmaceutical Research & Development in La Jolla, California. In 2003, he established his research group at Rutgers New Jersey Medical School, where he rose through the ranks and became a tenured professor in 2014. Tian joined The Wistar Institute in 2020.

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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.


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Staff

Postdoctoral Fellows

Yange Cui, Ph.D.
Chuwei Zhong, Ph.D.
Luyang Wang, Ph.D.

Research Assistant

Qingbao Ding

Available Positions

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, btian@wistar.org.

Research

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

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. Learn More

APAlyzer_BinTian

APAlyzer is a bioinformatics program developed by the Tian lab for the analysis of APA isoform expression changes by using RNA-seq data. Learn More

MAAPER_finalBinTian

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.

Selected Publications

Cheng, L.C., Zheng, D., Zhang, Q., Guvenek, A., Cheng, H., Tian, B. “Alternative 3' UTRs Play A Widespread Role In Translation-independent mRNA Association With The Endoplasmic Reticulum." Cell Rep. 2021 Jul 20;36(3):109407. doi: 10.1016/j.celrep.2021.109407.
 

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., 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.

Wang, R., Zheng, D., Yehia, G., Tian, B. "A Compendium Of Conserved Cleavage And Polyadenylation Events In Mammalian Genes." Genome Res. 2018 Oct;28(10):1427-1441. doi: 10.1101/gr.237826.118. Epub 2018 Aug 24.

Zheng D., Wang, R., Ding, Q., Wang, T., Xie, B., Wei, L., Zhong, Z., Tian, B. "Cellular Stress Alters 3’UTR Landscape Through Alternative Polyadenylation And Isoform-specific Degradation." Nat Commun. 2018 Jun 11;9(1):2268. doi: 10.1038/s41467-018-04730-7.

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