The overarching Silverman laboratory goal is to apply her 20 years of experience with rodent model systems to design and implement effective translational science for neurodevelopmental disorders (NDDs) in four thematic areas. Her research uses multi-faceted approaches in order to: 1) define clinically relevant outcome measures and identify biological markers using next generation genetic models of intellectual disability (ID), autism spectrum disorders (ASD) and pediatric epilepsy with known genetic origins; 2) develop rigorous methods for phenotypic detection in rat models of NDDs and neurodegenerative disorders; 3) continue to evaluate the most prominent environmental contributors to risk of NDDs and neurodegenerative disorders; and 4) utilize innovative, non-behaviorally based phenotypes, such as ex and in vivo neuroimaging, and neurophysiology including EEG, sleep/circadian analysis and sleep spindle modulation, which are biomarkers and translationally relevant to the symptoms of multiple brain disorders.
A major goal of the Department of Psychiatry is fostering distinguished basic neuroscience research. Dr. Silverman’s translational research on the causes of, and development of treatments for, severe genetically based neurodevelopmental disorders (NDDs), is a timely and crucial component to the department. During this evaluation period, from 2017-2020, Dr. Silverman expanded her independent research program that uses novel preclinical rodent models and innovative assays for translational research to include several new techniques and to narrow down therapeutic discovery angles from the wide array of repurposed existing compounds to the development, validation, safety and efficacy testing of gene and stem cell based “curative, precision strategies,” for single gene caused NDDs, IDs and pediatric epilepsy. This shift from treatment screening to focused development of innovative cures occurred organically as the Silverman lab shifted from non-known causal or idiopathic ASDs to known genetic syndromic NDDs.
Child and Adolescent Psychiatry
B.A., Biology and Psychology, Rutgers University, New Brunswick NJ 1999
Postdoctoral Training, Behavioral Pharmacology, National Institute of Mental Health, Bethesda MD 2010
Ph.D., Neuroscience, University of Maryland, Baltimore School of Medicine, Baltimore MD 2006
California Institute for Regenerative Medicine (CIRM), DISC2 AAV9-Cas13 gene therapy for Angelman syndrome Role: co-I Segal PI (Segal),
RDM POSITIVE IMPACT FOUNDATION $1,250,000 05/01/2021-04/30/2024 Targeted Therapeutic Development Program for SYNGAP1-related Intellectual Disability Role: PI,
Foundation for Angelman Syndrome for Therapeutics (FAST) 01/01/2020-12/31/2025 $2,976,004 FAST Research Infrastructure Grant: Training the Next Generation of Angelman Syndrome Scientists Role: co-PI (Silverman, Segal),
NIH/NINDS 1R01NS097808-01A1$1,715,000 4/15/2017-1/31/2022 Phenotypic Characterization of Novel Models of Dup15q Syndrome Role: PI,
National Institute of Child Health and Human Development, MIND Institute Center for Excellence for Intellectual Disabilities, IDDRC, P50HD103526, (PI Abbeduto) 10/1/2013-5/31/2025 $1,300,000 Co-Investigator Jill L Silverman, Co-Director, Rodent Behavioral Core, Director, Mouse Behavioral Core,
Berg EL, Petkova SP, Born HA, Adhikari A, Anderson AE, Silverman JL. Insulin-like growth factor-2 does not improve behavioral deficits in mouse and rat models of Angelman Syndrome. Mol Autism. 2021 Sep 15;12(1):59. doi:10.1186/s13229-021-00467-1. PMID:34526125.
Berg EL, Shekib AJ, Petkova SP, Ellegood J, Fenton TA, Segal DJ, Gray JA, Wöhr M, Silverman JL. Excessive Laughter-like Vocalizations, Microcephaly, and Translational Outcomes in the Ube3a Deletion Rat Model of Angelman Syndrome. J Neuroscience. 2021 Sep 2:JN-RM-0925-21. doi:10.1523/JNEUROSCI.0925-21.2021. PMID:34475199.
Copping NA, McTighe SM, Fink KD, Silverman JL. Emerging Gene and Small Molecule Therapies for the Neurodevelopmental Disorder Angelman Syndrome. Neurotherapeutics. 2021 Jul;18(3):1535-1547. doi:10.1007/s13311-021-01082-x. Epub 2021 Sep 15. PMID:34528170.
Adhikari A, Copping NA, Beegle J, Cameron DL, Deng P, O'Geen H, Segal DJ, Fink KD, Silverman JL, Anderson JS. Functional rescue in an Angelman syndrome model following treatment with lentivector transduced hematopoietic stem cells. Hum Mol Genet. 2021 Jun 9;30(12):1067-1083. doi:10.1093/hmg/ddab104. PMID:33856035.
Haigh JL, Adhikari A, Copping NA, Stradleigh T, Wade AA, Catta-Preta R, Su-Feher L, Zdilar I, Morse S, Fenton TA, Nguyen A, Quintero D, Agezew S, Sramek M, Kreun EJ, Carter J, Gompers A, Lambert JT, Canales CP, Pennacchio LA, Visel A, Dickel DE, Silverman JL, Nord AS. Deletion of a non-canonical regulatory sequence causes loss of Scn1a expression and epileptic phenotypes in mice. Genome Med. 2021 Apr 26;13(1):69. doi:10.1186/s13073-021-00884-0. PMID:33910599.
Ellegood J, Petkova SP, Kinman A, Qiu LR, Adhikari A, Wade AA, Fernandes D, Lindenmaier Z, Creighton A, Nutter LMJ, Nord AS, Silverman JL, Lerch JP. Neuroanatomy and behavior in mice with a haploinsufficiency of AT-rich interactive domain 1B (ARID1B) throughout development. Mol Autism. 2021 Mar 23;12(1):25. doi:10.1186/s13229-021-00432-y. PMID:33757588.
Copping NA, Silverman JL. Abnormal electrophysiological phenotypes and sleep deficits in a mouse model of Angelman Syndrome. Molecular Autism. 2021 Feb 6;12(1):9. doi:10.1186/s13229-021-00416-y.
Berg EL, Pride MC, Petkova SP, Lee RD, Copping NA, Shen Y, Adhikari A, Fenton TA, Pedersen LR, Noakes LS, Nieman BJ, Lerch JP, Harris S, Born HA, Peters MM, Deng P, Cameron DL, Fink KD, Beitnere U, O'Geen H, Anderson AE, Dindot SV, Nash KR, Weeber EJ, Wöhr M, Ellegood J, Segal DJ, Silverman JL. Translational outcomes in a full gene deletion of ubiquitin protein ligase E3A rat model of Angelman syndrome. Transl Psychiatry. 2020 Jan 27;10(1):39. doi:10.1038/s41398-020-0720-2. PMID:32066685.
Copping NA, Adhikari A, Petkova SP, Silverman JL. Genetic backgrounds have unique seizure response profiles and behavioral outcomes following convulsant administration. Epilepsy Behav. 2019 Dec;101(Pt A):106547. doi:10.1016/j.yebeh.2019.106547. Epub 2019 Nov 4. PMID:31698263.
Copping NA, Christian SGB, Ritter DJ, Islam MS, Buscher N, Zolkowska D, Pride MC, Berg EL, LaSalle JM, Ellegood J, Lerch JP, Reiter LT, Silverman JL, Dindot SV. Neuronal overexpression of Ube3a isoform 2 causes behavioral impairments and neuroanatomical pathology relevant to 15q11.2-q13.3 duplication syndrome. Hum Mol Genet. 2017 Oct 15;26(20):3995-4010. doi:10.1093/hmg/ddx289. PMID:29016856.