John V. Moran, Ph.D.

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

4728 Med Sci II
1241 E. Catherine St. SPC 5618
Ann Arbor
MI
48109-5618
Phone: 
734-615-0456
Fax: 
734-763-3784
Email: 
moranj@umich.edu
Staff Support: 
Sue Kellogg
Research Interests: 

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.

Honors and Awards: 
Damon 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)
Basic Science Teaching Award in Human Genetics (2010)
Gilbert S. Omenn Collegiate Professorship in Human Genetics (2010)
Elected to Fellowship, American Association for the Advancement of Science (AAAS) (2012)
Curt Stern Award, American Society of Human Genetics (2013)
Education: 
Rochester Institute of Technology B.S. 1986 Chemistry
Ohio State University M.S. 1990 Molecular Genetics
University of Texas Southwestern Medical Center, Ph.D. 1994 Biochemistry
Selected Publications: 

Zhang, A., Dong, B., Doucet, A.J., Moldovan, J.B., Moran, J.V., and Silverman, R.H.: RNase L restricts the mobility of engineered retrotransposons in cultured human cells. Nucleic Acids Research, December 25, 2013 [Epub ahead of print]. Published as an open access article. PMCID in process.

Macfarlane, C.M., Collier, P., Rahbari, R., Beck, C.R., Wagstaff, J.F., Igoe, S., Moran, J.V., and Badge, R. M.: Transduction-specific ATLAS reveals a cohort of highly active L1 retrotransposons in human populations. Human Mutation, 34: 974-85, 2013. PMCID: PMC3880804

Wissing, S., Muñoz-Lopez, M., Macia, A., Yang, Z., Montano, M., Collins, W., Garcia-Perez, J.L., Moran, J.V., and Greene, W.C.: Reprogramming somatic cells into iPS cells activates LINE-1 retroelement mobility. Human Molecular Genetics, 21: 208-18, 2012. PMCID: PMC3235014

Kopera, H.C., Moldovan, J.B., Morrish, T.A., Garcia-Perez, J.L., and Moran, J.V.: Similarities between long interspersed element-1 (LINE-1) reverse transcriptase and telomerase. PNAS, 108: 20345-50, 2011. PMCID: PMC3251045

Coufal, N.G., Garcia-Perez, J.L., Peng, G.E., Marchetto, M.C., Muotri, A.R., Mu, Y., Carson, C.T., Macia, A., Moran, J.V., and Gage, F.H.: Ataxia telangiectasia mutated (ATM) modulates long interspersed element-1 (L1) retrotransposition in human neural stem cells. PNAS, 108: 20382-7, 2011. PMCID: PMC3251057

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, 12: 187-215, 2011. PMID: 21801021

Levin, H.L. and Moran, J.V.: Dynamic interactions between transposable elements and their hosts. Nature Reviews Genetics, 12: 615-27, 2011. PMCID: PMC3192332

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, October 7, 2010, 6: pii: e1001150. (*co-corresponding author). PMCID: PMC2951350

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. PMCID: PMC3034402

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. PMCID: PMC3013285 (Accompanied by comments in Cell, Nature Review Genetics, and Nature Methods).

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. PMCID: PMC2909034 (Accompanied by a “News and Views” article in Nature).

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. PMCID: PMC2593586

Garcia-Perez, J.L., Marchetto, M.C.N., Muotri, A.R., Coufal, N.G., 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 mechanism for trans-mediated mobilization of cellular RNAs by the LINE-1 reverse transcriptase. Genome Research, 17: 602-11, 2007. (*co-corresponding author).

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.

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.

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., Deng, W., Moran, J.V., and Gage, F.H.: L1 retrotransposition mediates somatic mosaicism in neuronal precursor cells. Nature, 435: 903-910, 2005. (Accompanied by a “News and Views” article in Nature).

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.

Gilbert, N., Bomar, J.M., Burmeister, M., and Moran, J.V.: Characterization of a mutagenic B1 retrotransposon insertion in the jittery mouse. Human Mutation, 24: 9-13, 2004.

Lutz, S.M., 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. Jr.: 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. (Cover article)

Morrish, T.A., Gilbert, N., Myers, J.S., Vincent, B.J., Stamato, T.D., Taccioli, G.E., Batzer, M.A., and Moran, J.V.: DNA repair mediated by endonuclease-independent LINE-1 retrotransposition. Nature Genetics, 31: 159-65, 2002. (Accompanied by a “News and Views” article in Nature Genetics).

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, E.S., 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. (Accompanied by “News and Views” articles in Science and Nature).

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. Jr., 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. Jr.: High frequency retrotransposition in cultured mammalian cells. Cell, 87: 917-27, 1996.