Jef D. Boeke, PhD
Retrotransposons; chromosome biology; synthetic chromosomes
Chromatin, Saccharomyces cerevisiae, LINE-1, retrotransposition, genome synthesis
My lab studies the biology of transposable DNA elements and their host: theeukaryotic chromosome. Transposable elements are agents of genome instability. We study retrotransposons which mobilize via RNA and reverse transcription. Because they are active in stem cells, and much less so in differentiated somatic cells, we are very interested in the mechanisms that control these elements. Moreover, retrotransposons pose a potential safety problem for stem cell therapies. We are also synthesizing designer chromosomes to tackle a variety of basic and clinically-oriented goals. In addition to leading the effort to synthesize an entirely synthetic yeast genome, designed in silico and built up from synthetic oligonucleotides, we are interested in harnessing the power of synthesis to build designer mammalian chromosomes for stem cell-based therapies. Specifically, we aim to build chromosomes that can be transferred to pigs to make them a safe source of human cells tissues and organs. We also aim to use synthetic chromosomes as a NextGen gene therapy vector potentially able to deliver hundreds of genes.
Cai Y, Agmon N, Choi WC, Ubide A, Stracquadanio G, Caravelli K, Hao H, Bader JS,
Boeke JD. 2015 Intrinsic biocontainment: Multiplex genome safeguards combine
transcriptional and recombinational control of essential yeast genes. Proc Natl Acad
Sci USA 112:1803-8.
Mitchell LA and Boeke JD, 2014 Circular permutation of a synthetic eukaryotic
chromosome with the telomerator. Proc Natl Acad Sci USA 111:17003-10.
Kuang Z, Cai L, Zhang X, Ji HK, Tu BJ, Boeke JD. 2014 A high-resolution view of
histone modifications and transcription across distinct metabolic states in budding
yeast. Nature Struct Molec Biol, 21:854-863.
Annaluru N, Muller H, Mitchell LA, … Bader JS, Boeke JD and Chandrasegaran S.
Total Synthesis of a Functional Designer Eukaryotic Chromosome, 2014 Science,
Taylor MS, LaCava J, Mita P, Molloy KR, Huang CRL, Li D, Adney EM, Jiang H,
Burns KH, Chait BT, Rout MP, Boeke JD, Dai L. 2013. Affinity proteomics reveals
human host factors implicated in discrete stages of LINE-1 retrotransposition. Cell,
O’Donnell KA, An W, Schrum CT, Wheelan SW, Boeke JD. 2013. Controlled
insertional mutagenesis using a LINE-1 (ORFeus) gene trap mouse model, Proc. Natl.
Acad. Sci. USA, 110:E2706-13.
Burns KH, Boeke JD. 2012 Human transposon tectonics, Cell, 149:740-52.
Dymond JS, Richardson SM, Coombes CE, Müller H, Annaluru N, Blake WJ,
Schwerzmann JW, Dai J, Lindstrom DL, Boeke AC, Gottschling D, Chandrasegaran
S, Bader JS, and Boeke JD. 2011. Synthetic chromosome arms function in yeast and
generate phenotypic diversity by design. Nature, 477:471-476.
Huang CRL, Schneider AM, Lu Y, Niranjan T, Shen P, Robinson, MA, Steranka, JP,
Valle D, Civin CI, Wang T, Wheelan SJ, Ji HK, Boeke JD, Burns KH Mobile
Interspersed repeats are major structural variants in the human genome. (2010) Cell
Dai J, Hyland EM, Yuan DS, Huang H, Bader JS and Boeke, JD 2008. Probing
nucleosome function: A highly versatile library of synthetic histone H3 and H4
mutants. Cell, 34:1066-78.