Michael J McConnell

Education

  • Postdoc, Stanford University
  • Postdoc, Harvard Medical School
  • PhD, University of California, San Diego
  • BS, North Carolina State University

Primary Appointment

  • Assistant Professor, Biochemistry and Molecular Genetics

Contact

Research Interest(s)

The Cause and Consequence of Somatic Mosaicism in Neurons

Research Description

The brain is a genetic mosaic. Neuron-to-neuron genomic differences - brought about by endogenous mobile element activity, by idiosyncratic sub-chromosomal amplifications and deletions, and by whole chromosome gains and losses – are hypothesized to “individualize” behavioral phenotypes. To explore the causes and consequences of genetic mosaicism in neural circuits, my laboratory develops high-throughput single cell approaches and employs these approaches to study human induced pluripotent stem cell (hiPSC)-derived neurons, as well as transgenic mice. We have three immediate research goals: 1) determine if genetic mosaicism leads to somatic selection during the development of neural circuits; 2) understand how genetic mosaicism affects the performance of neural circuits; and 3) discover genes that mediate the propensity for genetic mosaicism. Moreover, altered levels of mosaicism have been associated with neurodegenerative (e.g., Ataxia-telangiectasia) and neuropsychiatric disorders (e.g., schizophrenia and Rett’s syndrome). A deeper understanding of these and other neurological disorders is expected from ever-increasing understanding and measurement of neuronal genomic diversity.

Selected Publications

  • Grindberg R, Yee-Greenbaum J, McConnell M, Novotny M, O'Shaughnessy A, Lambert G, Araúzo-Bravo M, Lee J, Fishman M, Robbins G, Lin X, Venepally P, Badger J, Galbraith D, Gage F, Lasken R. RNA-sequencing from single nuclei. Proceedings of the National Academy of Sciences of the United States of America. 2013;110(49): 19802-7. PMID: 24248345 | PMCID: 24248345
  • McConnell M, Lindberg M, Brennand K, Piper J, Voet T, Cowing-Zitron C, Shumilina S, Lasken R, Vermeesch J, Hall I, Gage F. Mosaic copy number variation in human neurons. Science (New York, N.Y.). 2013;342(6158): 632-7. PMID: 24179226 | PMCID: 24179226
  • Singer T, McConnell M, Marchetto M, Coufal N, Gage F. LINE-1 retrotransposons: mediators of somatic variation in neuronal genomes? Trends in neurosciences. 2010;33(8): 345-54. PMID: 20471112 | PMCID: PMC2916067
  • Datwani A, McConnell M, Kanold P, Micheva K, Busse B, Shamloo M, Smith S, Shatz C. Classical MHCI molecules regulate retinogeniculate refinement and limit ocular dominance plasticity. Neuron. 2009;64(4): 463-70. PMID: 19945389 | PMCID: PMC2787480
  • McConnell M, Huang Y, Datwani A, Shatz C. H2-K(b) and H2-D(b) regulate cerebellar long-term depression and limit motor learning. Proceedings of the National Academy of Sciences of the United States of America. 2009;106(16): 6784-9. PMID: 19346486 | PMCID: PMC2672503
  • McConnell M, MacMillan H, Chun J. Mathematical modeling supports substantial mouse neural progenitor cell death. Neural development. 2009;4 28. PMID: 19602274 | PMCID: PMC2729736
  • McConnell M, Kaushal D, Yang A, Kingsbury M, Rehen S, Treuner K, Helton R, Annas E, Chun J, Barlow C. Failed clearance of aneuploid embryonic neural progenitor cells leads to excess aneuploidy in the Atm-deficient but not the Trp53-deficient adult cerebral cortex. The Journal of neuroscience : the official journal of the Society for Neuroscience. 2004;24(37): 8090-6. PMID: 15371510 | PMCID: 15371510
  • Rehen S, McConnell M, Kaushal D, Kingsbury M, Yang A, Chun J. Chromosomal variation in neurons of the developing and adult mammalian nervous system. Proceedings of the National Academy of Sciences of the United States of America. 2001;98(23): 13361-6. PMID: 11698687 | PMCID: PMC60876