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Dr. Jef Boeke

Ph.D., D.Sc.
Interests

Research interests: Mechanism and regulation of transposition of yeast and human mobile genetic elements; yeast as a model system for human disease; transcriptional silencing; functional genomics.

Titles

Founder and Director, HiT Center (High Throughput Biology Center)Professor of Molecular Biology and Genetics
Professor of Oncology

Schools\Degrees

Ph.D., Molecular Biology, Rockefeller University, New York

Training

Postdoctoral Fellow, The Whitehead Institute/Massachusetts Institute of Technology

Research Summary

Dr. Boeke recently became the founding director of Hopkins’ High Throughput Biology Center (HiT Center), an interdisciplinary center embracing new technologies and including computational biologists, neuroscientists and molecular biologists. His laboratory has spearheaded a multilaboratory effort to map all genetic interactions encoded in the yeast genome. The main intellectual focus of the Boeke laboratory is retrotransposons in yeast, namely the Ty1 element, and in human cells, namely the L1 or LINE elements. Yeast is used because a combined genetic and biochemical approach can be readily used to analyze complex processes like transposition. Retrotransposons move to new sites in the genome via reverse transcription, using a process called retrotransposition that is mechanistically similar to retroviral replication. Ty1 even specifies the formation of viruslike particles in the cytoplasm of yeast cells; these particles, which contain Ty1 RNA and proteins, are retrotransposition intermediates. 

The roles of both Ty1-encoded and host-encoded functions in retrotransposition are being studied genetically. Studies on host mutants have identified components of a variety of apparently unrelated cellular pathways, such as RNA processing and translation. Factors that determine target site specificity of transposition in vivo and in vitro are a major focus. Other biochemical studies are focused on reverse transcription, which occurs in a diversity of biological systems as well as cellular telomere replication and the DNA integration process. Increasingly, similar strategies are used to understand the retrotransposition mechanism of the human L1 element, which, although it multiplies by a reverse transcription mechanism, is much less like retroviruses than Ty1. In fact, the detailed mechanism is not yet known but probably involves target-site nick-primed reverse transcription. Recent studies on these elements suggest that they can have a profound impact on gene expression in mammalian cells. Finally, it has been possible to construct synthetic retrotransposons that are superactive, generating a novel tool for mammalian genetic studies of various types.

Journal Citations

Lin, Y.Y.; Lu, J.Y.; Zhang, J.; Walter, W.; Dang, W.; Wan, J.; Tao, S.C.; Qian, J.; Zhao, Y.; Boeke, J.D.; Berger, S.L.; Zhu, H. Protein acetylation microarray reveals that NuA4 controls key metabolic target regulating gluconeogenesis. Cell. 2009 Mar 20;136(6):1073-1084.

Huang, C.R.; Schneider, A.M.; Lu, Y.; Niranjan, T.; Shen, P.; Robinson, M.A.; Steranka, J.P.; Valle, D.; Civin, C.I.; Wang, T.; Wheelan, S.J.; Ji, H.; Boeke, J.D.; Burns, K.H. Mobile interspersed repeats are major structural variants in the human genome. Cell. 2010 Jun 25;141(7):1171-1182.

 

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