Postdoctoral position to study miRNAs and alternative polyadenylation Eric Lai Lab, Sloan Kettering Institute, NYC, USA

2021年02月15日

A postdoctoral position is available to study mechanisms and biology of post-transcriptional regulation. Some current topics of particular interest in the lab include (1) dysregulation of miRNA biogenesis in cancer and (2) tissue-specific alternative polyadenylation.

1. miRNA biogenesis and function. miRNAs are a vital class of regulatory RNA, but much remains to be learned of their regulation and function. We are intrigued by hotspot DICER1 mutations that recur in tumors. We and others found these impair RNaseIIIb activity, but why this is advantageous to cancer cells is unknown. We now generated novel DICER1 knock-in mutants in hESCs, which are poised to reveal their molecular impacts in different celltypes and identify critical misregulated driver genes. Our group also studies other mechanisms of miRNA regulation and miRNA biology.

Recent papers on miRNA regulation and function

Vedanayagam J., W. K. Chatila, B. A. Aksoy, S. Majumdar, A. J. Skanderup, E. Demir, N. Schultz, C. Sander and E. C. Lai (2019). Cancer-associated mutations in DICER1 RNase IIIa and IIIb domains exert similar effects on miRNA biogenesis. Nature Communications 10: 3682. doi: 10.1038/s41467-019-11610-1.

Shang, R., S. Baek, K. Kim, B. Kim, V. N. Kim, and E. C. Lai (2020). Genomic clustering aids nuclear processing of suboptimal pri-miRNA loci. Molecular Cell 78: 303-316.

Bejarano, F., C.-H. Chang, K. Sun, J.W. Hagen, W.-M. Deng, and E. C. Lai (2021). A comprehensive in vivo screen for anti-apoptotic miRNAs indicates broad capacities for oncogenic synergy. Developmental Biology, accepted in principle.

2. Alternative polyadenylation (APA). Most genes express multiple 3'UTR isoforms, which exhibit variation across development, perturbations, and disease. However, we still know few factors that drive APA, and even less about in vivo biology of APA. Recently, we uncovered one of the first mechanisms that broadly confers a tissue-specific APA landscape (massive 3'UTR extension in neurons via ELAV/Hu RBPs), and showed how loss of neural APA from a single gene impairs behavior. We are excited to further elucidate APA strategies in Drosophila and mammals.

Recent papers on APA mechanism and biology

Wei, L., S. Lee, S. Majumdar, B. Zhang, P. Sanfilippo, B. Joseph, P. Miura, M. Soller and E. C. Lai (2020). Overlapping Activities of ELAV/Hu Family RNA Binding Proteins Specify the Extended Neuronal 3' UTR Landscape in Drosophila. Molecular Cell 80: 140-155.

Garaulet, D.L., B. Zhang, L. Wei, E. Li, and E. C. Lai (2020). A post-transcriptional regulatory circuit specifies the virgin behavioral state. Developmental Cell 54: 410-423.

Lee, S., B. Zhang, L. Wei, R. Goering, S. Majumdar, J. M. Taliaferro, and E. C. Lai (2020). Overlapping activities of ELAV/Hu RNA binding proteins determine multiple neural alternative splicing programs. BIORXIV/2020.09.21.305912v1.

The ideal candidate will have experience in biochemistry, CRISPR methods, and/or genomics, and will take advantage of extensive unpublished tools and resources to probe one (or both) of these areas. We have an interactive, supportive, and collaborative team engaged in diverse RNA topics, and the Sloan Kettering Institute provides a vibrant research community that promotes inclusivity and diversity. Generously funded position with housing and medical benefits is available immediately. Please provide CV, motivation letter and references to Eric Lai, このメールアドレスはスパムボットから保護されています。閲覧するにはJavaScriptを有効にする必要があります。.

https://www.mskcc.org/research/ski/labs/eric-lai

Twitter: @lucksmith

 

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