Gail Mandel, Ph.D.
Biography
Gail Mandel is senior scientist at the Vollum Institute and a professor in the Department of Biochemistry and Molecular Biology in the School of Medicine at OHSU. A valley girl at heart, she received her Ph.D. in Immunology from the University of California, Los Angeles in 1977, four years after receiving her B.A. in Biology. Mandel did her postdoctoral training at UCLA and the University of California, San Diego. She was an instructor in the Department of Pathology at Harvard Medical School for two years before joining Molecular Medicine at Tufts-New England Medical Center in 1984. In 1989, Mandel was promoted to associate professor in the Department of Neurobiology & Behavior at Stony Brook University and advanced to the rank of distinguished professor before joining the Vollum Institute in 2006. She was an HHMI Investigator from 1997 to 2016.
Summary of current research
The Mandel Lab research is focused on understanding how neuronal cell identity is established and maintained. Unexpectedly, the lab discovered that this is achieved primarily through a repressor mechanism. At the heart of this mechanism lies the DNA-binding protein, REST. Together with its interaction partners, REST controls the epigenetic status of neuronal gene chromatin. Knowledge of this mechanism provides a window into the molecular events governing nervous system formation.
The lab is exploiting embryonic stem cell differentiation and knock out animals to understand how the repressor complex is regulated during normal development. Using a novel strategy for characterizing transcription factor binding sites, they elucidated the REST genetic network and are studying how this network, and its associated chromatin signature, direct normal neuronal differentiation and contributes to autism spectrum disorders. Most recently, the Mandel lab extended their studies to explore neuronal-glial interactions, uncovering a role for glia in inducing neuronal dysfunction in Rett Syndrome, one of the most common causes of mental retardation in young girls. Their goal is to identify how the glial genes or proteins cause the underlying neuronal pathology.
Jacobsen CS, Salvador P, Yung JF, Kragness S, Mendoza HG, Mandel G, Beal PA. (2023) Library Screening Reveals Sequence Motifs That Enable ADAR2 Editing at Recalcitrant Sites. ACS Chem Biol.. acschembio.3c00107.
Nichols RV, O'Connell BL, Mulqueen RM, Thomas J, Woodfin AR, Acharya S, Mandel G, Pokholok D, Steemers FJ, Adey AC. (2022) High-throughput robust single-cell DNA methylation profiling with sciMETv2. Nat Commun. 13(1):7627.
Sinnamon JR, Jacobson ME, Yung JF, Fisk JR, Jeng S, McWeeney SK, Parmelee LK, Chan CN, Yee SP, Mandel G. (2022) Targeted RNA editing in brainstem alleviates respiratory dysfunction in a mouse model of Rett syndrome. Proc Natl Acad Sci U S A. 119(33):e2206053119.
McGann JC, Spinner MA, Garg SK, Mullendorff KA, Woltjer RL, Mandel G. (2021) The genome-wide binding profile for human RE1 Silencing Transcription factor unveils a unique genetic circuitry in hippocampus. J. Neurosci. Jun 29:JN-RM-2059-20 [Online ahead of print]
Sinnamon JR, Kim SY, Fisk JR, Song Z, Nakai H, Jeng S, McWeeney SK, Mandel G. (2020) In vivo repair of a protein underlying a neurological disorder by programmable RNA editing. Cell Reports 32(2):107878.
Sinnamon JR, Torkenczy KA, Linhoff MW, Vitak SA, Mulqueen RM, Pliner HA, Trapnell C, Steemers FJ, Mandel G, Adey AC. (2019) The accessible chromatin landscape of the murine hippocampus at single-cell resolution. Genome Res. 29:857-869.
Rakela B, Brehm P, Mandel G. (2018) Astrocytic modulation of excitatory synaptic signaling in a mouse model of Rett syndrome. Elife 7:e31629.
Sinnamon JR, Kim SY, Corson GM, Song Z, Nakai H, Adelman JP, Mandel G. (2017) Site-directed RNA repair of endogenous Mecp2 RNA in neurons. Proc. Natl. Acad. Sci. USA 114:E9395-E9402.
Monaghan CE, Nechiporuk T, Jeng S, McWeeney SK, Wang J, Rosenfeld MG, Mandel G. (2017) REST corepressors RCOR1 and RCOR2 and the repressor INSM1 regulate the proliferation-differentiation balance in the developing brain. Proc. Natl. Acad. Sci. USA 114:E406-E415.
Du F, Nguyen MV, Karten A, Felice CA, Mandel G, Ballas N. (2016) Acute and crucial requirement for MeCP2 function upon transition from early to late adult stages of brain maturation. Hum. Mol. Genet. 25:1690-1702.
Rakela B, Brehm P, Mandel G. (2018) Astrocytic modulation of excitatory synaptic signaling in a mouse model of Rett syndrome. Elife 7:e31629.
Sinnamon JR, Kim SY, Corson GM, Song Z, Nakai H, Adelman JP, Mandel G. (2017) Site-directed RNA repair of endogenous Mecp2 RNA in neurons. Proc. Natl. Acad. Sci. USA 114:E9395-E9402.
Linhoff MW, Garg SK, Mandel G. (2015) A high-resolution imaging approach to investigate chromatin architecture in complex tissues. Cell 163:246-255.
Lioy DT, Garg S, Monaghan C, Raber J, Foust K, Kaspar B, Hirrlinger P, Kirchhoff F, Bissonnette J, Ballas N, Mandel G. (2011) A role for glia in the progression of Rett Syndrome. Nature 475:497-500.
Ballas N, Grunseich C, Lu DD, Speh JC, Mandel G. (2005) REST and its corepressors mediate plasticity of neuronal gene chromatin throughout neurogenesis. Cell 121:645-657.
Toledo-Aral JJ, Moss BL, He ZJ, Koszowski AG, Whisenand T, Levinson SR, Wolf JJ, Silos-Santiageo I, Halegoua S, Mandel G. (1997) Identification of PN1, a predominant voltage-dependent sodium channel expressed principally in peripheral neurons. Proc. Natl. Acad. Sci. USA 94:1527-1532.
Chong, JA, Tapia-Ramírez J, Kim S, Toledo-Aral JJ, Zheng Y, Boutros MC, Altshuller YM, Frohman MA, Kraner SD, Mandel G. (1995) REST: a mammalian silencer protein that restricts sodium channel gene expression to neurons. Cell 80:949-957.
Toledo-Aral JJ, Brehm P, Halegoua S, Mandel G. (1995) A single pulse of nerve growth factor triggers long-term neuronal excitability through sodium channel gene induction. Neuron 14:607-611.
Trimmer JS, Cooperman SS, Tomiko SA, Zhou JY, Crean SM, Boyle MB, Kallen RG, Sheng ZH, Barchi RL, Sigworth FJ, Goodman RH, Agnew W, Mandel G. (1989) Primary structure and functional expression of a mammalian skeletal muscle sodium channel. Neuron 3:33-49.
Salkoff L, Butler A, Wei A, Scavarda N, Giffen K, Ifune C, Goodman R, Mandel G. (1987) Genomic organization and deduced amino acid sequence of a putative sodium channel gene in Drosophila. Science 237:744-749.