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11月14日清华大学生物论坛 - Uttiya Basu
发布时间:2017-11-07关键字:

  Noncoding RNA transcription regulation in B cell genomic integrity and organization

 

 

Uttiya Basu, Ph.D. 

Associate Professor of Microbiology and Immunology,Columbia University.

 

 

Abstract: The immune system responds to a universe of pathogenic organisms and non-self molecules by generating antibodies with almost infinite diversity. B-lymphocytes accomplish this task by carrying out three remarkable DNA alteration processes: VDJ recombination, somatic hypermutation (SHM), and class switch recombination (CSR). V(D)J recombination on immature B lymphocytes in the bone marrow dramatically increases the immunoglobulin (Ig) repertoire; subsequently, B cells migrate to secondary lymphoid organs where they undergo SHM, increasing the affinity of an immunoglobulin for cognate epitopes, and CSR, tailoring the effector function triggered by a specific antigen-recognizing antibody. These last two genetic alterations depend on the single stranded (ss)DNA cytidine deaminase, AID. The DNA mutator AID catalyzes both CSR--by initiating the generation of DNA double strand breaks in the immunoglobulin heavy chain locus (IgH) switch sequences (IgS)—and SHM (by incorporating point mutations in the immunoglobulin variable region genes). However, AID can also accidentally create DNA lesions in the B cell genome, potentially causing B cell malignancies.  AID’s activity is regulated, among other factors, by the cellular non-coding RNA processing pathway complex RNA exosome. Using a mouse model in which RNA exosome activity can be conditionally deleted, we have found that genomic regions targeted by AID express a subset of antisense non-coding RNAs and that these regions demonstrate bidirectional transcription. In addition, we have also identified regions in the B cell genome that express various long non-coding RNAs and these AID target DNA sequences are hypermutated by AID. In sum, our laboratory investigates how transcription of non-coding RNAs may influence AID-induced B cell genome mutagenesis that ultimately leads to B cell lymphomagenesis. Our work has implications in the fields of B cell mediated immunity, B cell oncogenesis, and regulation of the non-coding RNA transcriptome.

 

 

 

Biography: Uttiya Basu received his Ph.D. degree in Molecular Biology from Albert Einstein College of Medicine in 2004. After finishing postdoctoral training in the laboratory of Dr. Frederick Alt at Harvard Medical School in 2009, he joined the faculty of Columbia University, Department of Microbiology and Immunology. His laboratory utilizes technologies involving genome engineering, genomics and biochemistry. His research is focused on the various mechanisms by which non-coding RNA transcription controls genome architecture in pluripotent and differentiated mammalian cells. He has been awarded the NIH director’s New Innovators Award, the Leukemia Lymphoma Society Career Development award, the Pershing Square Sohn Cancer Research Alliance prize, Irvington Institute and Cancer research institute post doctoral fellowship and Lymphoma Research Foundation Award for cancer research.

 

Time: Nov. 14th, 2017, 15:00

Venue: New Biology Building, Room 143

Host: Prof. Haiteng Deng

举办单位:生命科学联合中心

 

 

 

 




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