John V. Moran, Ph.D.
Gilbert S. Omenn Collegiate Professor of Human Genetics
Professor of Human Genetics and Internal Medicine
Investigator, Howard Hughes Medical Institute
The goal of our laboratory is to understand how an abundant class of "jumping genes," known as retrotransposable elements, impacts the structure and function of human genomes. In particular, we study Long INterspersed Element-1 (LINE-1 or L1) retrotransposons. The average human genome is estimated to contain roughly 80-100 LINE-1 elements that are able to mobilize (i.e., retrotranspose) to new genomic locations by a copy and paste mechanism termed target-site primed reverse transcription. On occasion, LINE-1 retrotransposition events can disrupt gene function and de novo LINE-1 insertions have led to sporadic cases of genetic disease. During the past decade, we have used genetic, molecular biological, biochemical, and genomic technologies to learn more about LINE-1 element biology. We currently are using these technologies to address the following questions: 1) How does L1 retrotranspose? 2) How do LINE-1 retrotransposition events impact the human genome? 3) How do cellular factors promote or restrict LINE-1 retrotransposition? 4) How does LINE-1 retrotransposition contribute to intra- and inter-individual genetic variation? We currently have openings for motivated graduate students and postdoctoral fellows who are interested in helping us answer the above questions.
Beck, C.R., Garcia-Perez, J.L., Badge, R.M. and Moran, J.V.: LINE-1 Elements in structural variation and disease. Annual Review of Genomics and Human Genetics, in press.
Levin, H. and Moran, J.V.: Dynamic interactions between transposable elements and their hosts. Nature Reviews Genetics, 12: 615-27, 2011.
Doucet, A.J., Hulme, A.E., Sahinovic, E., Kulpa, D.A., Moldovan, J.B., Kopera, H.C., Athanikar, J.N., Hasnaoui M., Bucheton, A., Moran, J.V.*, and Gilbert, N.: Characterization of LINE-1 ribonucleoprotein particles. PLoS Genetics, Published October 7, 2010, 6: pii: e1001150. (*Co-corresponding author).
Garcia-Perez, J.L., Morell, M., Scheys, J.O., Kulpa, D.A., Morell, S., Carter, C.C., Hammer, G.D., Collins, K.L., O?Shea, K.S., Menendez, P., and Moran, J.V.: Epigenetic silencing of engineered L1 retrotransposition events in human embryonic carcinoma cells. Nature, 466: 769-73, 2010.
Beck, C.R., Collier, P., Macfarlane, C., Malig, M., Kidd, J.M., Eichler, E.E., Badge, R.M., and Moran, J.V.: LINE-1 retrotransposition activity in human genomes. Cell, 141: 1159-70, 2010.
Coufal, N.G., Garcia-Perez, J.L., Peng, G.E., Yeo, G.W., Mu, Y, Lovci, M.T., Morell, M., O'Shea, K. S., Moran, J.V., and Gage, F.H.: L1 retrotransposition in human neural progenitor cells. Nature, 460, 1127-31, 2009.
Bennett, E.A., Keller, H., Mills, R.E., Schmidt, S., Moran, J.V., Weichenrieder, O., and Devine, S.E.: Active Alu retrotransposons in the human genome. Genome Research, 18, 1875-83, 2008.
Garcia-Perez, J.L., Marchetto, M.C.N., Muotri, A.R., Coufal, N., Gage, F.H., O'Shea, K.S., and Moran, J.V.: LINE-1 retrotransposition in human embryonic stem cells. Human Molecular Genetics, 16, 1569-77, 2007.
Garcia-Perez, J.L., Doucet, A.J., Bucheton, A., Moran, J.V.*, and Gilbert, N.: Distinct mechanisms for trans-mediated mobilization of cellular RNAs by the LINE-1 reverse transcriptase. Genome Research, 17, 602-11, 2007. (*Co-corresponding author)
Hulme, A.E., Bogerd, H.P., Cullen, B.R., and Moran, J.V.: Selective inhibition of Alu retrotransposition by APOBEC3G. Gene, 390, 199-205, 2007.
Morrish, T.A., Garcia-Perez, J.L., Stamato, T.D., Taccioli, G.E., Sekiguchi, J., and Moran, J.V.: Endonuclease-independent LINE-1 retrotransposition at mammalian telomeres. Nature, 446, 208-12, 2007.
Kulpa, D.A. and Moran, J.V.: Cis-preferential LINE-1 reverse transcriptase activity in ribonucleoprotein particles. Nature Structural and Molecular Biology, 13, 655-60, 2006.
Bogerd, H.P., Wiegand, H.L., Hulme, A.E., Garcia-Perez, J.L., O'Shea, K.S. Moran, J.V., and Cullen, B.R.: Cellular inhibitors of long interspersed element 1 and Alu retrotransposition. PNAS, 103, 8780-5, 2006.
Alisch, R.S., Garcia-Perez, J.L., Muotri, A.R., Gage, F.H., and Moran, J.V.: Unconventional translation of mammalian LINE-1 retrotransposons. Genes and Development, 20, 210-24, 2006.
Muotri, A.R., Chu, V.T., Marchetto, M.C.N., Deng, W., Moran, J.V., and Gage, F.H.: Somatic mosaicism in neuronal precursor cells mediated by L1 retrotransposition. Nature, 435, 903-910, 2005.
Kulpa, D.A. and Moran, J.V.: Ribonucleoprotein particle formation is necessary but not sufficient for LINE-1 retrotransposition. Human Molecular Genetics, 14, 3237-48, 2005.
Gilbert, N., Lutz, S., Morrish, T.A., and Moran, J.V.: Multiple fates of L1 retrotransposition intermediates in cultured human cells. Molecular and Cellular Biology, 25, 7780-95, 2005.
Athanikar, J.N., Badge, R.M., and Moran, J.V.: A YY1-binding site is required for accurate human LINE-1 transcription initiation. Nucleic Acids Research, 32, 3846-55, 2004.
Lutz, S. Vincent, B.J., Kazazian, H.H., Jr., Batzer, M.A., and Moran, J.V.: Allelic heterogeneity in LINE-1 retrotransposition activity. American Journal of Human Genetics, 73, 1431-37, 2003.
Brouha, B., Schustak, J., Badge, R.M., Lutz-Prigge, S., Farley, A.H., Moran, J.V., and Kazazian, H.H.: Hot L1s account for the bulk of retrotransposition in the human population. PNAS, 100, 5280-85, 2003.
Badge R.M., Alisch, R.S., and Moran, J.V.: ATLAS: a system to selectively identify human-specific LINE-1 insertions. American Journal of Human Genetics, 72, 823-838, 2003.
Gilbert, N., Lutz-Prigge, S., and Moran, J.V.: Genomic deletions created upon LINE-1 retrotransposition. Cell, 110, 315-325, 2002.
Morrish, T.A., Gilbert, N., Myers, J.S., Vincent, B.J., Stamato, T., Taccioli, G., Batzer, M.A., and Moran, J.V.: DNA repair mediated by endonuclease-independent LINE-1 retrotransposition. Nature Genetics, 31, 159-65, 2002.
Wei, W., Gilbert, N., Ooi, S-L, Lawler, J.F., Ostertag, E.M., Kazazian, H.H., Boeke, J.D., and Moran, J.V.: Human L1 retrotransposition: cis-preference vs. trans-complementation. Molecular and Cellular Biology, 21, 1429-39, 2001.
Lander et al., International Human Genome Sequencing Consortium: Initial sequencing and analysis of the human genome. Nature, 409, 860-921, 2001. (We contributed to the sections regarding the analysis of repeats in human DNA. Specifically, we identified the young "active" L1s present in the genome draft and characterized them in various ways).
Moran, J.V., DeBerardinis, R.J., and Kazazian, H.H. Jr.: Exon shuffling by L1 retrotransposition. Science 283, 1530-34, 1999.
Kazazian, H.H. Jr. and Moran, J.V.: The impact of L1 retrotransposons on the human genome. Nature Genetics 19, 19-24, 1998.
Feng, Q., Moran, J.V., Kazazian, H.H. and Boeke, J.D.: Human L1 retrotransposon encodes a conserved endonuclease required for retrotransposition. Cell 87, 905-16, 1996.
Moran, J.V., Holmes, S.E., Naas, T.P., DeBerardinis, R.J., Boeke, J.D. and Kazazian, H.H.: High frequency retrotransposition in cultured mammalian cells. Cell 87, 917-27, 1996.