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Faculty
Research InterestsOur research focuses on a class of human 'jumping genes' known as Long Interspersed Element-1 sequences (LINE-1s). LINE-1s comprise ~17% of human DNA. The vast majority of LINE-1s are mutated and are no longer mobile; however, ~100 elements in the average human genome retain the ability to 'jump'. On occasion, deleterious 'jumps' can result in various genetic diseases, including Hemophilia A, muscular dystrophy, and colon cancer. My laboratory is interested in learning more about the biology of LINE-1s. Using genetic, molecular biological and biochemical approaches, we are addressing the following questions: 1) How, when, and where do LINE-1s 'jump'? 2) What is the impact of LINE-1 'jumping' on the human genome? 3) What host factors promote or restrict LINE-1 mobility? 4) How does LINE-1 retrotransposition activity vary among individuals? Our long-term goal is to gain a better understanding about how LINE-1 jumping leads to human disease and how this process has influenced the evolution of our genome. Education1978-1982 Sachem High School, Lake Ronkonkoma, NY 1982-1986 Rochester Institute of Technology, Rochester, NY, BS (graduated with high honors in Chemistry) 1986-1990 The Ohio State University, Columbus, OH, M.S. (Molecular Genetics; mentor: Philip S. Perlman) 1990-1994 The University of Texas Southwestern Medical Center, Dallas, TX, Ph.D. (Biochemistry; mentor: Philip S. Perlman) Postgraduate Training1994 Postdoctoral Fellow in Pediatrics, The Johns Hopkins University School of Medicine, Baltimore, MD (Laboratory of Dr. Haig H. Kazazian Jr.) 1994-1998 Postdoctoral Fellow in Genetics, The University of Pennsylvania School of Medicine, Philadelphia, PA (Laboratory of Dr. Haig H. Kazazian Jr.) Honors and AwardsDamon Runyon/Walter Winchell Postdoctoral Fellowship (1995) University of Michigan Biomedical Scholars Program (1998) Basil O'Connor Starter Scholar Research Award (2000) Damon Runyon Scholar Award (2000) W. M. Keck Foundation Distinguished Young Scholars in Medical Research Award (2000) University of Michigan Henry Russel Award (2003) Co-organizer FASEB Conference on Mammalian Mobile Elements (2005) Co-organizer Symposium on Transposable Elements at the Salk Institute (2005) Co-organizer Symposium on the Genomic Impact of Eukaryotic Transposable Elements (2006) Main Organizer FASEB Conference on Mammalian Mobile Elements (2007) Dean’s Basic Science Research Award, University of Michigan Medical School (2007) Investigator, Howard Hughes Medical Institute (2008) Recent Publications 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. 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. Lab ProjectsPlease contact Dr. Moran for information regarding current research projects. Additional Lab LinksCellular and Molecular Biology Program Howard Hughes Medical Institute (HHMI)
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