Susan Ackerman, PhD

Understanding the molecular pathways that control neuron homeostasis in the mammalian brain

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.

 

Ishimura R, Nagy G, Dotu I, Chuang JH, Ackerman SL. Activation of GCN2 by ribosome stalling links translation elongation with translation initiation. eLife. 2016. e14295.

Liu Y, Lee JW, Ackerman SL. Mutations in the microtubule-associated protein 1A (Map1a) gene cause Purkinje cell degeneration. J Neurosci. 2015. 35:4587-98.

Jia Y, Jucius TJ, Cook SA, Ackerman SL. Loss of Clcc1 results in ER stress, misfolded protein accumulation, and neurodegeneration. J Neurosci. 2015. 35:3001-9.

Liu Y, Satz JS, Vo MN, Nangle LA, Schimmel P, Ackerman SL. Deficiencies in tRNA synthetase editing activity cause cardioproteinopathy. Proc Natl Acad Sci U S A. 2014. 111:17570-5.

Ishimura R, Nagy G, Dotu I, Zhou H, Yang XL, Schimmel P, Senju S, Nishimura Y, Chuang JH, Ackerman SL. RNA function. Ribosome stalling induced by mutation of a CNS-specific tRNA causes neurodegeneration. Science. 2014. 345:455-9.

Liu Y, Zaun HC, Orlowski J, Ackerman SL. CHP1-mediated NHE1 biosynthetic maturation is required for Purkinje cell axon homeostasis. J Neurosci. 2013. 33:12656-69.

Jia Y, Mu JC, Ackerman SL. Mutation of a U2 snRNA gene causes global disruption of alternative splicing and neurodegeneration. Cell. 2012 148:296-308.

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.