Gail Mandel, Ph.D.
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.
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.
Linhoff MW, Garg SK, and Mandel G. (2015) A high-resolution imaging approach to investigate chromatin architecture in complex tissues. Cell 163:246-255.
Cargnin F, Nechiporuk T, Müllendorff K, Stumpo DJ, Blackshear P, Ballas N, and Mandel G. (2014) An RNA binding protein promotes axonal integrity in peripheral neurons by destabilizing REST. J. Neurosci. 34:16650-16661.
McGann JC, Oyer JA, Garg S, Yao H, Liu J, Feng X, Liao L, Yates JR 3rd, and Mandel G. (2014) Polycomb- and REST-associated histone deacetylases are independent pathways toward a mature neuronal phenotype. Elife 3:e04235.
Nesti E, Corson GM, McCleskey M, Oyer JA, and Mandel G. (2014) C-terminal domain small phosphatase 1 and MAP kinase reciprocally control REST stability and neuronal differentiation. Proc. Natl. Acad. Sci. 111:e3929-3936.
Garg SK, Lioy DT, Cheval H, McGann JC, Bissonnette JM, Murtha MJ, Foust KD, Kaspar BK, Bird A, and Mandel G. (2013) Systemic delivery of MeCP2 rescues behavioral and cellular deficits in female mouse models of Rett syndrome. J. Neurosci. 33:13612-13620.
Mongeon R, Walogorsky M, Urban J, Mandel G, Ono F, and Brehm P. (2011) An acetylcholine receptor lacking both the γ and ε subunits mediates transmission in zebrafish slow muscle synapses. J. Gen. Physiology 138:353-366.
Lioy DT, Garg S, Monaghan C, Raber J, Foust K, Kaspar B, Hirrlinger P, Kirchhoff F, Bissonnette J, Ballas N, and Mandel G. (2011) A role for glia in the progression of Rett Syndrome. Nature 475:497-500.
Ballas N, Lioy DT, Grunseich C, and Mandel G. (2009) Non-cell autonomous influence of MeCP2-deficient glia on neuronal dendritic morphology. Nature Neurosci. 12:311-317. (News & Views in Nature Neurosci. 2009, 12:239-240.)
Karginov FV, Conaco C, Xuan Z, Schmidt BH, Parker JS, Mandel G, and Hannon GJ. (2007) A biochemical approach to identifying microRNA targets. Proc. Natl. Acad. Sci. USA 104:19291-19296.
Otto SJ, McCorkle SR, Hover J, Conaco C, Han J-J, Impey S, Yochum GS, Dunn JJ, Goodman RH, and Mandel G. (2007) A new binding motif for the transcriptional repressor REST uncovers large gene networks devoted to neuronal function. J. Neurosci. 27:6729-6739.