John Moran, Ph.D.

John V. Moran, Ph.D.

Gilbert S. Omenn Collegiate Professor
Professor of Human Genetics
Professor of Internal Medicine 

4728 Med Sci II
1241 E. Catherine St. SPC 5618
Ann Arbor, MI 48109-5618

moranj@umich.edu
734-615-0456
Articles ↓ Web Sites ↓

Areas of Interest

The goal of our laboratory is to understand how an abundant class of "jumping genes," known as retrotransposons, affects 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 ~80-100 active LINE-1s 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. Since starting my laboratory at the University of Michigan, we have used genetic, molecular biological, biochemical, and modern genomic and computational approaches to address the following questions: 1) What is the molecular mechanism of LINE-1 retrotransposition? 2) How do LINE-1 retrotransposition events affect the human genome? 3) What cellular factors promote or restrict LINE-1 retrotransposition? 4) How does LINE-1 retrotransposition contribute to intra- and inter-individual genetic variation? We welcome motivated graduate students and postdoctoral fellows to join our team. Please contact Dr. Moran ([email protected]) if you are interested in learning more about our research.

Honors & Awards

  • University of Michigan Endowment for Basic Sciences Accelerator Award (with Dr. Jeffrey Kidd) (2021)
  • University of Michigan Medical School Distinguished Faculty Lectureship in Biomedical Research (2019)
  • American Society of Human Genetics Board of Directors (2019 – 2021)
  • American Society of Human Genetics Program Committee (2017 – 2018)
  • Co-Organizer, The Mobile Genome: Genetic and Physiological Impacts of Transposable Elements, EMBL Heidelberg, Germany (2015, 2017, & 2021)
  • Elected to the League of Research Excellence, University of Michigan Medical School (2014)
  • Curt Stern Award, American Society of Human Genetics (2013)
  • Elected to Fellowship, American Association for the Advancement of Science (AAAS) (2012)
  • Standing Study Section Member for the NIH Genetic Variation & Evolution Study Section (2010-2015)
  • Basic Science Teaching Award in Human Genetics, University of Michigan Medical School (2010)
  • Gilbert S. Omenn Collegiate Professorship in Human Genetics (2010)
  • Investigator, Howard Hughes Medical Institute (2008-2016)
  • American Society of Human Genetics Awards Committee (2007 – 2009)
  • Dean's Basic Science Research Award, University of Michigan Medical School (2007)
  • Co-organizer Symposium on the Genomic Impact of Eukaryotic Transposable Elements (2006)
  • Co-organizer Symposium on Transposable Elements at the Salk Institute (2005)
  • Co-organizer FASEB Conference on Mammalian Mobile Elements (2005 & 2007)
  • University of Michigan Henry Russel Award (2003)
  • Kavli Fellow, National Academy of Sciences (2002)
  • W. M. Keck Foundation Distinguished Young Scholars in Medical Research Award (2000-2005)
  • Damon Runyon Scholar Award (2000)
  • Basil O'Connor Starter Scholar Research Award (2000)
  • Postdoctoral Basic Science Research Award, The American Society of Human Genetics (1998)
  • University of Michigan Biomedical Scholars Program (1998-present)
  • Damon Runyon/Walter Winchell Postdoctoral Fellowship (1995-1997)

Credentials

  • Gilbert S. Omenn Collegiate Professorship in Human Genetics, Ann Arbor, MI (12/02/2010-present)
  • Professor, University of Michigan Medical School, Ann Arbor, MI (9/01/08-present)
  • Scientific Advisory Board Member and Consultant, Tessera Therapeutics Inc., Boston, MA (2020-present)
  • Consultant, Gilead Sciences, Inc., Foster City, CA (2019-present)
  • Investigator, Howard Hughes Medical Institute (8/01/08-1/31/16)
  • Associate Professor, University of Michigan Medical School, Ann Arbor, MI (9/01/03-8/31/08)
  • Assistant Professor, University of Michigan Medical School, Ann Arbor, MI (10/98-8/31/03)
  • Postdoctoral Fellow, University of Pennsylvania Medical School, Philadelphia, PA (8/94-9/98)
  • Postdoctoral Fellow, Johns Hopkins University Medical School, Baltimore, MD (5/94-8/94)
  • University of Texas Southwestern Medical Center, Ph.D., Biochemistry (1994)
  • Ohio State University M.S., Molecular Genetics (1990)
  • Rochester Institute of Technology B.S. Chemistry (1986)

Published Articles or Reviews

Luqman-Fatah, A., Watanabe, Y., Ishikawa, F., Moran, J.V., and Miyoshi, T.: The interferon stimulated gene-encoded protein HELZ2 inhibits human LINE-1 retrotransposition and LINE-1 RNA-mediated type I interferon induction. Nature Communications, 14: 493, 2023. PMID: 36639706. PMCID: PMC9839780.

Mortimer, S.M., Frisbie, T.J., Moldovan, J.B., Nakamura, M., Sandwith, S.N., Yin, J., and Moran, J.V.: “Chromosomes: noncoding DNA (including satellite DNA)” in Encyclopedia of Life Sciences. Published September 27, 2022.

Ward, J.R., Khan, A., Torres, S., Crawford, B., Nock, S., Frisbie, T., Moran, J.V., and Longworth, M.S.: Condensin I and condensin II proteins form a LINE-1 dependent super condensin complex and cooperate to repress LINE-1. Nucleic Acids Research, 50: 10680-10694, 2022. PMID: 36169232. PMCID: PMC9561375.

Moran, J.V. and Wilson, T.E.: Reverse transcriptase meets DNA, again: Possible roles for transposable elements in host DNA repair. Cell, 185: 3643-45, 2022 (Preview article). PMID: 36179663. DOI: 10.1016/j.cell.2022.09.012

Zhu, X., Zhou, B., Pattni, R., Gleason, K., Tan, C., Kalinowski, A, Sloan, S., Fiston-Lavier, A.S., Mariani, J., Petrov, D., Barres, B.A., Duncan, L., Abyzov, A., Vogel, H., Brain Somatic Mosaicism Network, Moran, J.V., Vaccarino, F.M., Tamminga, C.A., Levinson, D.F., and Urban, A.E.: Machine learning reveals bilateral distribution of somatic L1 insertions in human neurons and glia. Nature Neuroscience, 24: 186-196, 2021. PMCID: PMC8806165

Wang, Y., Bae, T., Thorpe, J.  Sherman M.A., Jones  A.G. (…other authors), Brain Somatic Mosaicism Network, Vaccarino F.M., Moran J.V., Urban A.E., Pevsner J., Kidd J.M., Mills R.E., Abyzov A.: Comprehensive identification of somatic nucleotide variants in human brain tissue, Genome Biology, 22: 92. doi: 10.1186/s13059-021-02285-3, 2021. PMCID: PMC8006362 (I am a member of the Brain Somatic Mosaicism Network).

Halo, J.V.*, Pendleton, A.L.*, Shen, F.*, Doucet, A.J., Derrien, T., Hitte, C., Laura Kirby, L.E., Myers, B., Sliwerska, E., Emery, S., Moran, J.V., Boyko, A.R, and Kidd, J.M.: Long-read assembly of a Great Dane genome highlights the contributions of GC-rich sequence and mobile elements to canine genomes. PNAS, 118: e2016274118. doi: 10.1073/pnas.2016274118, 2021. PMCID: PMC7980453

Zhou, W., Emery, S.B., Flasch, D.A., Wang, Y., Kwan, K.Y., Kidd, J.M., Moran, J.V., and Mills, R.E.: Identification and characterization of occult human-specific LINE-1 insertions using long-read sequencing technology, Nucleic Acids Research, 48: 1146-63, 2020. PMCID: PMC7026601

Moldovan, J.B., Wang, Y., Shuman, S., Mills, R.E., and Moran. J.V.: RtcB mediates the ligation of U6 snRNA and LINE-1 RNA prior to retrotransposition. PNAS, 116: 20612-20622, 2019. PMCID: PMC6789731

Miyoshi, T., Makino, T., and Moran, J.V.: Poly(ADP-ribose) polymerase 2 recruits replication protein A to sites of LINE-1 integration to facilitate retrotransposition. Molecular Cell, 75: 1286-98, 2019. PMCID: PMC6754305

Flasch, D.A., Macia Á., Sánchez, L., Ljungman, M., Heras, S.R., García-Pérez, J.L., Wilson, T.E., and Moran, J.V.: Endonuclease Activity and a Replication Association Promote Widespread L1 Retrotransposition Throughout the Human Genome. Cell, 177: 837-851, 2019. PMCID: PMC6558663 (Accompanied by a commentary in Molecular Cell).

Larson, P.A., Molodovan, J.B., Jasti, N., Kidd, J.M., Beck, C.R. and Moran, J.V.: Spliced Integrated Retrotransposed Element Formation in the Human Genome. PLoS Biology, 16: e2003067, 2018. PMCID: PMC5860796

Ward, J.R., Vasu, K., Halawani, D., Deutschman, E., Larson, P.A., Zhang, D., Willard, B., Fox, P.L., Moran, J.V., and Longworth, M.S.: Repression of LINE-1 retrotransposition through cooperation of Condensin II and GAIT complexes in epithelial cells. PLoS Genetics, 13: e1007051, 2017. PMCID: PMC5656329

Kazazian, H.H. Jr. and Moran, J.V.: Mobile DNA in health and disease. New England Journal of Medicine, 377: 361-70, 2017. PMCID: PMC5980640

McConnell M.J.*, Moran J.V.*, Abyzov A., Akbarian S., Bae T., Cortes-Ciriano I., Erwin J.A., Fasching L., Flasch D.A., Freed D., Ganz J., Jaffe A.E., Kwan K.Y., Kwon M., Lodato M.A., Mills R.E., Paquola A.C.M., Rodin R.E., Rosenbluh C., Sestan N., Sherman M.A., Shin J.H., Song S., Straub R.E., Thorpe J., Weinberger D.R., Urban A.E., Zhou B., Gage F.H., Lehner T., Senthil G., Walsh C.A., Chess A., Courchesne E., Gleeson J.G., Kidd J.M., Park P.J., Pevsner J., Vaccarino F.M., Brain Somatic Mosaicism Network: Intersection of diverse neuronal genomes and neuropsychiatric disease: The Brain Somatic Mosaicism Network. Science, Apr 28; 356(6336). pii: eaal1641. doi: 10.1126/science.aal1641. Epub 2017, Apr 27. PMCID: PMC5558435. *Co-first and co-corresponding authors.

Kopera, H.C., Larson, P.A., Moldovan, J.B., Richardson, S.R., Liu, Y., and Moran, J.V.: LINE-1 Cultured Cell Retrotransposition Assay. Methods Mol. Biol., 1400: 139-56, 2016. PMCID: PMC5070806

Kopera, H.C., Flasch, D.A., Nakamura, M., Miyoshi, T., Doucet, A.J., and Moran, J.V.: LEAP: L1 Element Amplification Protocol. Methods Mol. Biol., 1400: 339-55, 2016. PMCID: PMC5070798

Doucet, A.D., Wilusz, J.E., Miyoshi, T., Liu, Y., and Moran, J.V.: A 3’ poly(A) tract is required for LINE-1 retrotransposition. Molecular Cell, 60: 728-41, 2015. PMCID: PMC4671821 (Accompanied by comments in Molecular Cell).

Moldovan, J.B. and Moran, J.V.: The zinc-finger antiviral protein ZAP inhibits LINE and Alu retrotransposition. PLoS Genetics, May 7;11(5):e1005121, 2015. PMCID: PMC4423928

Richardson, S.R., Narvaiza, I., Planegger, R.A., Weitzman, M.D., and Moran, J.V.: APOBEC3A deaminates transiently exposed single-strand DNA during LINE-1 retrotransposition. Elife, April 24; 3:e02008, 2014. PMCID: PMC4003774

Moran, J.V.: 2013 Curt Stern Award Address. American Journal of Human Genetics, 94: 340-48, 2013. PMCID: PMC395192

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

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

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

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

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

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).

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.

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.

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.

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.

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).

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.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).

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).

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.

Wei, W., Morrish, T.A., Alisch, R.S., and Moran, J.V.: A transient assay reveals that cultured human cells can accommodate multiple LINE-1 retrotransposition events. Analytical Biochemistry, 284: 435-38, 2000.

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.

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.

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.

 

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