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McConnell, Michael

Michael McConnell

Primary Appointment

Biochemistry and Molecular Genetics

Contact Information

PO Box 800733
Charlottesville, VA 22908
Telephone: (434) 924-0154
Fax: (434) 924-5069
Email: mjm2zv@virginia.edu
Website: http://www.mcconnell-lab.org

Research Interests

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

McConnell MJ, Lindberg MR, Brennand KJ, Piper JC, Voet T, Cowing-Zitron C, Shumilina S, Lasken RS, Vermeesch JR, Hall IM, Gage FH, Mosaic copy number variation in human neurons., 2013; Science (New York, N.Y.). 342(6158) 632-7 PMID: 24179226 | PMCID: 24179226

Grindberg RV, Yee-Greenbaum JL, McConnell MJ, Novotny M, O'Shaughnessy AL, Lambert GM, Ara?zo-Bravo MJ, Lee J, Fishman M, Robbins GE, Lin X, Venepally P, Badger JH, Galbraith DW, Gage FH, Lasken RS, RNA-sequencing from single nuclei., 2013; Proceedings of the National Academy of Sciences of the United States of America. 110(49) 19802-7 PMID: 24248345 | PMCID: 24248345

Singer T, McConnell MJ, Marchetto MC, Coufal NG, Gage FH, LINE-1 retrotransposons: mediators of somatic variation in neuronal genomes?, 2010; Trends in neurosciences. 33(8) 345-54 PMID: 20471112 | PMCID: PMC2916067

Datwani A, McConnell MJ, Kanold PO, Micheva KD, Busse B, Shamloo M, Smith SJ, Shatz CJ, Classical MHCI molecules regulate retinogeniculate refinement and limit ocular dominance plasticity., 2009; Neuron. 64(4) 463-70 PMID: 19945389 | PMCID: PMC2787480

McConnell MJ, MacMillan HR, Chun J, Mathematical modeling supports substantial mouse neural progenitor cell death., 2009; Neural development. 4() 28 PMID: 19602274 | PMCID: PMC2729736

McConnell MJ, Huang YH, Datwani A, Shatz CJ, H2-K(b) and H2-D(b) regulate cerebellar long-term depression and limit motor learning., 2009; Proceedings of the National Academy of Sciences of the United States of America. 106(16) 6784-9 PMID: 19346486 | PMCID: PMC2672503

McConnell MJ, Kaushal D, Yang AH, Kingsbury MA, Rehen SK, Treuner K, Helton R, Annas EG, 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., 2004; The Journal of neuroscience : the official journal of the Society for Neuroscience. 24(37) 8090-6 PMID: 15371510 | PMCID: 15371510

Rehen SK, McConnell MJ, Kaushal D, Kingsbury MA, Yang AH, Chun J, Chromosomal variation in neurons of the developing and adult mammalian nervous system., 2001; Proceedings of the National Academy of Sciences of the United States of America. 98(23) 13361-6 PMID: 11698687 | PMCID: PMC60876