Jeffrey A. Golden, M.D.

faculty photo
Adjunct Professor of Pathology and Laboratory Medicine
Department: Pathology and Laboratory Medicine

Contact information
The Children’s Hospital of Philadelphia
Room 5135 - Main
34th Street and Civic Center Boulevard
Philadelphia, PA 19104
Office: (215) 590-4446
Fax: (215) 590-1021
B.A. (Biochemistry)
University of California, San Diego, La Jolla, CA, 1983.
M.D. (Medicine)
University of Pennsylvania, Philadelphia, PA, 1988.
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Description of Research Expertise

Research Interests
• Cell migration and specification in the developing nervous system
• Animal models of human neurodevelopmental disorders
• Pathogenesis of developmental epilepsies

Development, embryonic patterning, gene expression, cell migration, CNS malformations, epilepsy, seizures, neuropathology

Research Summary
My laboratory is interested in understanding multiple aspects of early nervous system development. A major focus is on the molecular and cellular mechanisms of neuronal migration. Disruptions in migration are associated with a broad range of human disorders including lissencephaly, developmental epilepsies, intellectual disabilities, and autism. We use a combination of in vivo and in vitro methods to investigate the guidance, mechanisms of movement, and genes regulating neuronal migration. Most recently we have been probing animal models with mutations in genes known to result in human migration disorders. Mutations in both LIS1 and ARX give rise to a spectrum of human neurodevelopmental disorders. Using available animal models, and animal models we have developed, along with human tissue, our studies have provided new insights into normal neurodevelopment and the pathogenesis of phenotypes observed in children. Two recent areas of focus include exploring the intracellular signaling and cytoskeletal dynamics required for cell migration and the transcriptional networks required for regulating neuronal migration.

A related area of investigation includes the transcriptional and cell signaling pathways required for neuronal differentiation as it relates to human developmental disorders. We recently identified a novel human intellectual disability susceptibility gene. Using both in vivo and in vitro systems we have defined the role for this gene in BMP signaling and forebrain cholinergic neuron differentiation. We are using this model to test novel, biologically based, treatments for intellectual disabilities.

Rotation Projects for 2010-2011
Various cell and molecular biology projects related to cell migration and differentiation in the developing nervous system.

Research Techniques
Mouse and chick embryological studies using modern cellular and molecular techniques along with genetic and surgical manipulation of embryos.

Lab personnel:
Rachel Martin, Lab Manager
Ginam Cho, Ph.D., Research Associate
George Clement, Technician
Erika Lin-Hendel, Graduate Student
Dan Lysko, Graduate Student
River McCullar, Undergraduate Student
Jacqueline Simonet, Graduate Student
Nicole Sunnen, Ph.D., Postdoc

Selected Publications

Gopal P, Simonet J, Shapiro W, Golden JA: Leading Process Branch Instability in Lis1+/- Nonradially Migrating Interneurons. Cerebral Cortex 20(6): 1497-505, 2010.

Amado D, Mingozzi F, Hui D, Bennicelli JL,Wei Z, Chen Y, Bote E, Grant RL, Golden JA, Narfstrom K, Syed NA, Orlin SE, High KA, Maguire AM, Bennett J: Safety and Efficacy of Subretinal Re-Administration of a Viral Vector in Large Animals to Treat Congenital Blindness. Science Translational Medicine 2(21): 21ra16, 2010.

Cho G, Lim, Y and Golden JA: Sumo interaction motifs in sizn1 are required for pml-nb Localization and transcriptional activation. J Biol Chem 284(29): 19592-600, Jul 2009.

Lin W, Ye W, Cai L, Meng X, Ke G, Huang C, Peng Z, Yu Y, Golden JA, Tartakoff AM, Tao T: The roles of multiple importins for nuclear import of murine aristaless-related homeobox protein. J Biol Chem 284(30): 20428-39, Jul 2009.

Marsh E, Golden JA: Developing an animal model for infantile spasms: pathogenesis, problems, and progress. Disease Models and Mechanisms 2(7-8): 329-35, Jul-Aug 2009.

Marsh E, Fulp C, Gomez E, Nasrallah I, Minarcik J, Sudi J, Christian SL, Mancini G, Labosky P, Dobyns W, Brooks-Kayal A, Golden JA : Targeted loss of Arx results in a developmental epilepsy mouse model and recapitulates the human phenotype in heterozygous females Brain 132(Pt 6): 1563-76, Jun 2009.

Buccafusca R, Venditti CP, Kenyon LC, Johanson RA, Van Bockstaele E, Ren J, Pagliardini S, Minarcik J, Golden JA, Coady MJ, Greer JJ, Berry GT: Characterization of the null murine sodium/myo-inositol cotransporter 1 (Smit1 or Slc5a3) phenotype: myo-inositol rescue is independent of expression of its cognate mitochondrial ribosomal protein subunit 6 (Mrps6) gene and of phosphatidylinositol levels in neonatal brain. Mol. Genet. Metabol. 95(1-2): 81-95, 2008.

Cho G, Bhat SS, Gao J, Collins JS, Rogers RC, Simensen RJ, Schwartz CE, Golden JA, Srivastava AK: Evidence that SIZN1 is a Candidate X-Linked Mental Retardation Gene. Am J Med Genetics 146A: 2644-50, 2008.

Najm J, Horn D, Wimplinger I, Golden JA, Chizhikov V, Sudi J, Christian SL, Ullmann R, Kuechler A, Haas CA, Flubacher A, Charnas LA, Uyanik G, Frank U, Klopocki E, William B. Dobyns WB, Kutsche K: Mutations of CASK cause a novel X-linked brain malformation phenotype with microcephaly and hypoplasia of the brainstem and cerebellum. Nature Genetics 40: 1065-7, 2008.

Marsh ED, Minarcik J, Campbell K, Brooks-Kayal AR, Golden JA: FACS-array gene expression analysis during early development of mouse telencepehalic interneurons. Dev Neurobiol 68: 434-45, 2008.

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Last updated: 02/25/2012
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