Elliott Sherr, MD, PhD

Director, Comprehensive Center for Brain Development
Professor
Department of Neurology
SherrE@neuropeds.ucsf.edu

The lab uses a variety of tools (genetics, imaging, animal models) to study two important clinical domains: autism and epilepsy. We not only seek to discover the causes of these conditions but to develop new treatments. Below is a sampling of ongoing projects.

Ongoing Research: 

The genetics of epilepsy: We have focused on a specific group of epilepsies, the epileptic encephalopathies (EE), that can be associated with autism and intellectual disability. We recently published a manuscript (Nature. 2013; 501(7466): 217-21. PMID: 23934111) that used exome sequencing in family trios to identify novel EE genes and to show that de novo genetic mutations are key for pathogenesis. We are using similar tools as well as animal models (including using CRISPR tools for mutagenesis) to discover new causes and to study the specific mutations found in patients.

Genetics First Approach to Autism: The 16p11.2 copy number variations (CNV; both deletion and duplication) are two of the most common genetic events associated with autistic spectrum disorder (ASD). We lead a network of scientists  (SVIP; http://www.simonsvipconnect.org/) investigating the brain imaging changes (MRI, fMRI, MEG) and cognitive, and behavioral features of individuals with 16p11.2 deletions or duplications. By studying a group of individuals who all share the same genetic change, we hope to discover novel insights that explain how disrupted brain function can lead to the specific behavioral and cognitive changes associated with ASD. A recent publication (PMID: 24790192) highlights the potential of this approach.

Development of Blood-based biomarkers for autism: Advances in autism genetics and in the study of animal models provide evidence to suggest that some biochemical pathways are commonly affected in autistic patients. Our lab has shown that the activity level of specific selected intracellular signaling pathways are altered in ASD patients and that these measurements may be predictive of ASD status in presymptomatic children. Work is ongoing to elucidate the biology underlying these observations.

Gene discovery in human brain malformations: Our lab has shown that de novo and inherited genetic events play an important role in causing disorders of cerebral development, specifically focusing on patients with agenesis of the corpus callosum (ACC). ACC has a strong association with autism, as exemplified by Kim Peek, who has ACC and whose life was fictionalized in the movie, Rain Man. When novel ACC genes are identified, we develop animal models to investigate the implications on cerebral development. (See: PMID: 24098143 and PMID: 23453666).

Primary Thematic Area: 
Human Genetics
Secondary Thematic Area: 
Neurobiology
Research Summary: 
The genetics of autism and epilepsy: studies in cerebral development and connectivity

Websites

Publications: 

Linking tuberous sclerosis complex, excessive mTOR signaling, and age-related neurodegeneration: a new association between TSC1 mutation and frontotemporal dementia.

Acta neuropathologica

Olney NT, Alquezar C, Ramos EM, Nana AL, Fong JC, Karydas AM, Taylor JB, Stephens ML, Argouarch AR, Van Berlo VA, Dokuru DR, Sherr EH, Jicha GA, Dillon WP, Desikan RS, De May M, Seeley WW, Coppola G, Miller BL, Kao AW

Brain MR Imaging Findings and Associated Outcomes in Carriers of the Reciprocal Copy Number Variation at 16p11.2.

Radiology

Owen JP, Bukshpun P, Pojman N, Thieu T, Chen Q, Lee J, D'Angelo D, Glenn OA, Hunter JV, Berman JI, Roberts TP, Buckner R, Nagarajan SS, Mukherjee P, Sherr EH

ARHGEF9 disease: Phenotype clarification and genotype-phenotype correlation.

Neurology. Genetics

Alber M, Kalscheuer VM, Marco E, Sherr E, Lesca G, Till M, Gradek G, Wiesener A, Korenke C, Mercier S, Becker F, Yamamoto T, Scherer SW, Marshall CR, Walker S, Dutta UR, Dalal AB, Suckow V, Jamali P, Kahrizi K, Najmabadi H, Minassian BA

Mutations in DCC cause isolated agenesis of the corpus callosum with incomplete penetrance.

Nature genetics

Marsh AP, Heron D, Edwards TJ, Quartier A, Galea C, Nava C, Rastetter A, Moutard ML, Anderson V, Bitoun P, Bunt J, Faudet A, Garel C, Gillies G, Gobius I, Guegan J, Heide S, Keren B, Lesne F, Lukic V, Mandelstam SA, McGillivray G, McIlroy A, Méneret A, Mignot C, Morcom LR, Odent S, Paolino A, Pope K, Riant F, Robinson GA, Spencer-Smith M, Srour M, Stephenson SE, Tankard R, Trouillard O, Welniarz Q, Wood A, Brice A, Rouleau G, Attié-Bitach T, Delatycki MB, Mandel JL, Amor DJ, Roze E, Piton A, Bahlo M, Billette de Villemeur T, Sherr EH, Leventer RJ, Richards LJ, Lockhart PJ, Depienne C

Corrigendum: Mutations in SNORD118 cause the cerebral microangiopathy leukoencephalopathy with calcifications and cysts.

Nature genetics

Jenkinson EM, Rodero MP, Kasher PR, Uggenti C, Oojageer A, Goosey LC, Rose Y, Kershaw CJ, Urquhart JE, Williams SG, Bhaskar SS, O'Sullivan J, Baerlocher GM, Haubitz M, Aubert G, Barañano KW, Barnicoat AJ, Battini R, Berger A, Blair EM, Brunstrom-Hernandez JE, Buckard JA, Cassiman DM, Caumes R, Cordelli DM, De Waele LM, Fay AJ, Ferreira P, Fletcher NA, Fryer AE, Goel H, Hemingway CA, Henneke M, Hughes I, Jefferson RJ, Kumar R, Lagae L, Landrieu PG, Lourenço CM, Malpas TJ, Mehta SG, Metz I, Naidu S, Õunap K, Panzer A, Prabhakar P, Quaghebeur G, Schiffmann R, Sherr EH, Sinnathuray KR, Soh C, Stewart HS, Stone J, Van Esch H, Van Mol CE, Vanderver A, Wakeling EL, Whitney A, Pavitt GD, Griffiths-Jones S, Rice GI, Revy P, van der Knaap MS, Livingston JH, O'Keefe RT, Crow YJ