Christopher Donnelly, Ph.D.

  • Assistant Professor
  • Scientific Director-LiveLikeLou Center for ALS Research
  • Department of Neurobiology

Education & Training

  • B.S., Biological Sciences, Drexel University- 2005
  • Ph.D.,Molecular Biology and Genetics, University of Delaware-2011
  • Post-doctoral Fellowship, Molecular Mechanisms of Neurological Disease, Johns Hopkins University-2015

Research Interest Summary

To study the basic cellular processes whose dysfunction drive neurological disorders with a focus on liquid-liquid phase separation, RNA metabolism, and subcellular trafficking.

Research Categories

Research Interests

The Donnelly lab studies RNA metabolism, subcellular RNA and proteins trafficking in neurons, and biochemical interactions that drive liquid-liquid phase separation of proteins. We investigate how genetic or molecular perturbations in these cellular processes contribute to age-dependent neurodegeneration in motor neuron disease, Amyotrophic Lateral Sclerosis (ALS) and dementias, such as Frontotemporal Dementia (FTD) and Alzheimer’s Disease. A common neuropathological feature of these diseases is the presence of intracellular protein aggregates. Therefore, we are particularly interested in understanding how dysfunction in RNA processing, subcellular trafficking, and aberrant liquid-liquid phase separation promote the formation of these misfolded proteins and to develop strategies for therapeutic intervention. Our lab employs a molecular and cellular approach that includes the use of induced pluripotent stem cell cultures, optogenetics, longitudinal and confocal microscopy, RNA imaging, and biochemistry to achieve these goals. 

Representative Publications

Mann JR, Gleixner AM, Mauna JC, Gomes E, DeChellis-Marks MR, Needham PG, Copley KE, Hurtle B, Portz B, Pyles NJ, Guo L, Calder CB, Wills ZP, Pandey UB, Kofler JK, Brodsky JL, Thathiah A, Shorter J, Donnelly CJ. RNA Binding Antagonizes Neurotoxic Phase Transitions of TDP-43. Neuron. 2019 Apr 17;102(2):321-338.e8. doi: 10.1016/j.neuron.2019.01.048. Epub 2019 Feb 27. PubMed PMID: 30826182; PubMed Central PMCID: PMC6472983.

Choi IY, Lim H, Estrellas K, Mula J, Cohen TV, Zhang Y, Donnelly CJ, Richard JP, Kim YJ, Kim H, Kazuki Y, Oshimura M, Li HL, Hotta A, Rothstein J, Maragakis N, Wagner KR, Lee G. Concordant but Varied Phenotypes among Duchenne Muscular Dystrophy Patient-Specific Myoblasts Derived using a Human iPSC-Based Model. Cell Rep. 2016 Jun 7;15(10):2301-2312. doi: 10.1016/j.celrep.2016.05.016. Epub 2016 May 26. PubMed PMID: 27239027. 

Zhang K*, Donnelly CJ*, Haeusler AR, Grima JC, Machamer JB, Steinwald P, Daley EL, Miller SJ, Cunningham KM, Vidensky S, Gupta S, Thomas MA, Hong I, Chiu SL, Huganir RL, Ostrow LW, Matunis MJ, Wang J, Sattler R, Lloyd TE, Rothstein JD.The C9orf72 repeat expansion disrupts nucleocytoplasmic transport. Nature. 2015 Sep 3;525(7567):56-61. doi: 10.1038/nature14973. Epub 2015 Aug 26. PubMed PMID: 26308891; PubMed Central PMCID: PMC4800742. *authors share equal contribution.

Haidet-Phillips AM, Roybon L, Gross SK, Tuteja A, Donnelly CJ, Richard JP, Ko M, Sherman A, Eggan K, Henderson CE, Maragakis NJ. Gene profiling of human induced pluripotent stem cell-derived astrocyte progenitors following spinal cord engraftment. Stem Cells Transl Med. 2014 May;3(5):575-85. doi: 10.5966/sctm.2013-0153. Epub 2014 Mar 6. PubMed PMID: 24604284; PubMed Central PMCID: PMC4006486. 

Haeusler AR, Donnelly CJ, Periz G, Simko EA, Shaw PG, Kim MS, Maragakis NJ, Troncoso JC, Pandey A, Sattler R, Rothstein JD, Wang J. C9orf72 nucleotide repeat structures initiate molecular cascades of disease. Nature. 2014 Mar 13;507(7491):195-200. doi: 10.1038/nature13124. Epub 2014 Mar 5. PubMed PMID: 24598541; PubMed Central PMCID: PMC4046618. 

Donnelly CJ, Zhang PW, Pham JT, Haeusler AR, Mistry NA, Vidensky S, Daley EL, Poth EM, Hoover B, Fines DM, Maragakis N, Tienari PJ, Petrucelli L, Traynor BJ, Wang J, Rigo F, Bennett CF, Blackshaw S, Sattler R, Rothstein JD. RNA toxicity from the ALS/FTD C9ORF72 expansion is mitigated by antisense intervention. Neuron. 2013 Oct 16;80(2):415-28. doi: 10.1016/j.neuron.2013.10.015. PubMed PMID: 24139042; PubMed Central PMCID: PMC4098943.

Donnelly CJ, Park M, Spillane M, Yoo S, Pacheco A, Gomes C, Vuppalanchi D, McDonald M, Kim HH, Merianda TT, Gallo G, Twiss JL. Axonally synthesized β-actin and GAP-43 proteins support distinct modes of axonal growth. J Neurosci. 2013 Feb 20;33(8):3311-22. doi: 10.1523/JNEUROSCI.1722-12.2013. PubMed PMID: 23426659; PubMed Central PMCID: PMC3711152.

Spillane M, Ketschek A, Donnelly CJ, Pacheco A, Twiss JL, Gallo G. Nerve growth factor-induced formation of axonal filopodia and collateral branches involves the intra-axonal synthesis of regulators of the actin-nucleating Arp2/3 complex. J Neurosci. 2012 Dec 5;32(49):17671-89. doi: 10.1523/JNEUROSCI.1079-12.2012. PubMed PMID: 23223289; PubMed Central PMCID: PMC3596264. 

Willis DE*, Xu M*, Donnelly CJ*, Tep C, Kendall M, Erenstheyn M, English AW, Schanen NC, Kirn-Safran CB, Yoon SO, Bassell GJ, Twiss JL. Axonal Localization of transgene mRNA in mature PNS and CNS neurons. J Neurosci. 2011 Oct 12;31(41):14481-7. doi: 10.1523/JNEUROSCI.2950-11.2011. PubMed PMID: 21994364; PubMed Central PMCID: PMC3205917.  *authors share equal contribution.

Donnelly CJ*, Willis DE*, Xu M, Tep C, Jiang C, Yoo S, Schanen NC, Kirn-Safran CB, van Minnen J, English A, Yoon SO, Bassell GJ, Twiss JL. Limited availability of ZBP1 restricts axonal mRNA localization and nerve regeneration capacity. EMBO J.2011 Sep 30;30(22):4665-77. doi: 10.1038/emboj.2011.347. PubMed PMID: 21964071; PubMed Central PMCID: PMC3243598. *authors share equal contribution.

Full List of Publications