Susan Ackerman

Research

The goal of our laboratory is to define the molecular pathways necessary to maintain homeostasis in both developing and aging mammalian neurons. To do this we utilize forward genetics to identify mutations that are associated with loss of neurons in the aging mouse brain. To further dissect pathways underlying homeostatic disruption and disease, we also use forward genetics to identify genetic variants that enhance or suppress neural phenotypes. Our approach allows the identification, without a priori assumptions, of molecules critical for neuron homeostasis and survival, and indeed we have discovered disruptions in several novel pathways that were not previously associated with loss of neuronal function or survival. We are particularly interested in the role of alterations in translation elongation, translational fidelity, proteostasis, and RNA metabolism in neuronal function.

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Monaghan CE, Adamson SI, Kapur M, Chuang JH, Ackerman SL. (2021). The Clp1 R140H mutation alters tRNA metabolism and mRNA 3′ processing in mouse models of pontocerebellar hypoplasia .Proc Natl Acad Sci U S A. 18(39):e2110730118.
Terrey M, Adamson SI, Chuang JH, Ackerman SL. (2021). Defects in translation-dependent quality control pathways lead to convergent molecular and neurodevelopmental pathology. eLife 66904.
Cui H, Kapur M, Diedrich JK, Yates JR, Ackerman SL, Schimmel P. Regulation of ex-translational activities is the primary function of the multi-tRNA synthetase complex. Nucleic Acids Res. 2021 Apr 19;49(7):3603-3616. doi: 10.1093/nar/gkaa1183. PubMed PMID: 33341895; PubMed Central PMCID: PMC8053116.
Terry M, Adamson SI, Gibson A, Deng T, Ishimura R, Chuang J, Ackerman SL. (2020). GTPBP1 resolves paused ribosomes to maintain neuronal homeostasis. eLife 62731.
Kapur M, Ganguly A, Nagy G, Adamson SI, Chuang JH, Frankel WN, Ackerman SL. (2020). Expression of the neuronal tRNA n-Tr20 regulates synaptic transmission and seizure susceptibility . Neuron 108, 1–16.
Vo, M. N., Terrey, M., Lee, J. W., Roy, B., Moresco, J. J., Sun, L., Fu, H., Liu, Q., Weber, T. G., Yates, J. R., 3rd, Fredrick, K., Schimmel, P., & Ackerman, S L. (2018). ANKRD16 prevents neuron loss caused by an editing-defective tRNA synthetase. Nature, 557(7706), 510–515.
Kapur M, Ackerman SL. mRNA Translation Gone Awry: Translation Fidelity and Neurological Disease. Trends Genet. 2018 Mar;34(3):218-231. doi: 10.1016/j.tig.2017.12.007. Epub 2018 Jan 16. Review. PubMed PMID: 29352613; PubMed Central PMCID: PMC5834357.
Ishimura R, Nagy G, Dotu I, Chuang JH, Ackerman SL . (2016). Activation of GCN2 kinase by ribosome stalling links translation elongation with translation initiation . Elife e14295.
Jia Y, Jucius TJ, Cook SA, Ackerman SL . (2015). Loss of Clcc1 results in ER stress, misfolded protein accumulation, and neurodegeneration . J Neurosci 35:3001-9.
Liu Y, Lee JW, Ackerman SL. (2015). Mutations in the microtubule-associated protein 1A (Map1a) gene cause Purkinje cell degeneration. J Neurosci 35:4587-98.
Liu Y, Satz JS, Vo MN, Nangle LA, Schimmel P, Ackerman SL. (2014). Deficiencies in tRNA synthetase editing activity cause cardioproteinopathy. Proc Natl Acad Sci U S A 111:17570-5.
Ishimura, R., Nagy, G., Dotu, I., Zhou, H., Yang, X. L., Schimmel, P., Senju, S., Nishimura, Y., Chuang, J. H., & Ackerman, SL. (2014). RNA function. Ribosome stalling induced by mutation of a CNS-specific tRNA causes neurodegeneration. Science (New York, N.Y.), 345(6195), 455–459.
Liu Y, Zaun HC, Orlowski J, Ackerman SL. (2013). CHP1-mediated NHE1 biosynthetic maturation is required for Purkinje cell axon homeostasis. J Neurosci 33:12656-69.
Jia, Y., Mu, J. C., & Ackerman, SL. (2012). Mutation of a U2 snRNA gene causes global disruption of alternative splicing and neurodegeneration. Cell, 148(1-2), 296–308.
Zhao L, Spassieva SD, Jucius TJ, Shultz LD, Shick HE, Macklin WB, Hannun YA, Obeid LM, Ackerman SL. A deficiency of ceramide biosynthesis causes cerebellar Purkinje cell neurodegeneration and lipofuscin accumulation. PLoS Genet. 2011 (5):e1002063.
Kim D, Ackerman SL. The UNC5C netrin receptor regulates dorsal guidance of mouse hindbrain axons. J Neurosci. 2011 31:2167-79.
Zhao L, Rosales C, Seburn K, Ron D, Ackerman SL. Alteration of the unfolded protein response modifies neurodegeneration in a mouse model of Marinesco-Sjögren syndrome. Hum Mol Genet. 2010 19:25-35.
Lee, J. W., Beebe, K., Nangle, L. A., Jang, J., Longo-Guess, C. M., Cook, S. A., Davisson, M. T., Sundberg, J. P., Schimmel, P., & Ackerman, SL. (2006). Editing-defective tRNA synthetase causes protein misfolding and neurodegeneration. Nature, 443(7107), 50–55.
Klein, J. A., Longo-Guess, C. M., Rossmann, M. P., Seburn, K. L., Hurd, R. E., Frankel, W. N., Bronson, R. T., & Ackerman, SL. (2002). The harlequin mouse mutation downregulates apoptosis-inducing factor. Nature, 419(6905), 367-374.

Biography

Susan Ackerman received her Ph.D. from UCLA and was a postdoctoral fellow at University of Illinois Medical School and the Wistar Institute. Prior to her move to UCSD in 2016, Dr. Ackerman was a Professor at The Jackson Laboratory in Bar Harbor, Maine where she was a faculty member for nineteen years. She has been an Investigator of the Howard Hughes Medical Institute since 2005.