Research in my lab covers a broad range of human genetics from the identification of new disease causing genes to the development of new treatment options that are targeted to the underlying causes of disease. My group, along with large networks of collaborators, has been responsible for a number of well-known discoveries including the gene responsible for Alternating Hemiplegia of Childhood and the role of the IL28B gene in treatment response to Hepatitis C infection. As Director of the Sequencing, Biostatistics, and Bioinformatics Core for the Epi4K Consortium, I have led the collaboration that discovered three novel epilepsy genes. My group has also been involved in some of the early applications of next generation sequencing in the study of undiagnosed diseases and has discovered a number of new syndromes through the careful evaluation of individual patient genomes including NGLY1 deficiency and more recently the neurodevelopmental disease caused by mutation in GNB1. In addition to gene discovery, my group is also involved in the development of methods to aid the interpretation of genome sequence data including the first approach that used population genetic data to identify genes and genomic regions most likely to carry mutations that cause disease. This intolerance-scoring framework is now being refined not only to help discriminate benign and pathogenic mutations in genes but also to identify pathogenic mutations in non-coding parts of the genome. Finally, my lab is dedicated to the functional characterization of mutations that cause disease and to the development of in vitro modeling paradigms that are amendable to medium and high throughput screens to facilitate the identification of new treatment options for defined genetic conditions. A major focus in this regard is the genetic epilepsies where we are using cultured neuronal networks monitored with multi-electrode arrays (MEAs) to define clear, in vitro phenotypes for epilepsy mutations. Once we define such phenotypes we will screen both available drugs and indicated compounds to find candidate treatments based on the in vitro effects. The leading candidates will then be assessed in the appropriate mouse models and eventually in patients with the relevant genetic epilepsy.
- Identifying regulatory mutations that influence neuropsychiatric disease
- ALS Genome Sequencing Consortium with Biogen Idec
- An integrated and diverse genomic medicine program for undiagnosed diseases
- Epilepsy Genetics Initiative
- Epilepsy Genetics and disease mutation modeling
- Epi4K Center without walls: Sequencing, Biostatistics and Bioinformatics Core
- Epi4K: Gene Discovery in 4,000 Epilepsy Genomes
- EpiMiRNA: MicroRNAs in the Pathogenesis, Treatment and Prevention of Epilepsy
- Identification of Rare Variants of OCD
- Identifying de novo mutations causing OCD in trios by whole exome sequencing
- Healthcare provider organization site for the national Precision Medicine Initiative Cohort Program
- Anna Alkelai, Postdoctoral Scholar
- Chris Bostick, Postdoctoral Scholar
- Sophie Colombo, Associate Research Scientist
- Sahar Gelfman, Associate Research Scientist
- Diana Hall, Statistician
- Matthew Halvorsen, Postdoctoral Scholar
- Patrick Shea, Associate Research Scholar
- Nicholas Stong, UDN Bioinformatician
- Ryan Dhindsa, Graduate Student
- Sarah Dugger, Graduate Student
- Ayal Gussow, Graduate Student
- Daniel Krizay, Graduate Student
- Sarah Kleinstein, Graduate Student
- Yi-Fan Liu, Graduate Student
- Melodi McSweeney, Graduate Student
- Xiaolin Zhu, Graduate Student
- Epi4K Consortium
- Epilepsy Genetics Initiative
- Epigen Consortium
- The Jackson Laboratory Center for Precision Genetics: From New Models to Novel Therapeutics
- International Consortium research and care for the ATP1A3 diseases
- ALSGENS and GTAC ALS Genomics
- Petrovski S, Kury S, Myers CT, Anyane-Yeboa K, Cogne B, Bialer M, Xia F, Hemati P, Riviello J, et al, Goldstein DB. Germline de novo mutations in GNB1 cause severe neurodevelopmental disability, hypotonia and seizures. Am J Hum Genet. 2016, May 5;98(5):1001-10.
- Dhindsa RS, Goldstein DB. Schizophrenia: From genetics to physiology at last. Nature. 2016, Feb 11;530(7589)162-3.
- Lu YF, Mauger DM, Goldstein DB, Urban TJ, Weeks KM, Bradrick SS. IFNL3 mRNA structure is remodeled by a functional non-coding polymorphism associated with hepatitis C virus clearance. Sci Rep. 2015, Nov 4:5:16037. EpiPM Consortium. A roadmap for precision medicine in the epilepsies. Lancet Neurology. 2015, Dec 14(12):1219-28.
- Heinzen EL, Neale BM, Traynelis SF, Allen AS, Goldstein DB. Annu Rev Neurosci. 2015, Jul 8;38:47-68.
- Cirulli ET, Lasseigne BN, Petrovski S, Sapp PC, Dion PA, Leblond CS, et al, Goldstein DB. Exome sequencing in amyotrophic lateral sclerosis identifies risk genes and pathways. Science, 2015, Mar 27,347(6229):1436-41.
- EuroEPINOMICS-RES Consortium; Epilepsy Phenome/Genome Project; Epi4K Consortium. De Novo Mutations in Synaptic Transmission Genes Including DNM1 Cause Epileptic Encephalopathies. Am J Hum Genet. 2014, Oct 2;95(4):360-70.
- Epi4K Consortium and Epilepsy Phenome/Genome Project. De novo mutations in epileptic encephalopathies. Nature. 2013 Sep 12;501(7466):217-21.
- Heinzen EL*, Swoboda KJ*, Hitomi Y*, Gurrieri F, Nicole S, de Vries B, Tiziano FD, Fontaine B, Walley NM, Heavin S, Panagiotakaki E; European Alternating Hemiplegia of Childhood (AHC) Genetics Consortium; Biobanca e Registro Clinico per l'Emiplegia Alternante (I.B.AHC) Consortium; European Network for Research on Alternating Hemiplegia (ENRAH) for Small and Medium-sized Enterpriese (SMEs) Consortium, Fiori S, Abiusi E, et al, Goldstein DB. De novo mutations in ATP1A3 cause alternating hemiplegia of childhood. Nat Genet. 2012, Sep;44(9):1030-4.
- Ge D, Fellay J, Thompson AJ, Simon JS, et al, Goldstein DB. Genetic variation in IL28B predicts hepatitis C treatment-induced viral clearance. Nature. 2009, Sept 17;461(7262): 399-401.
- Heinzen EL*, Ge D*, Cronin KD, Maia JM, Shianna KV, Gabriel WN, Welsh-Bohmer KA, Hulette CM, Denny TN, Goldstein DB. Tissue-specific genetic control of splicing: Implications for the study of complex traits. PLoS Biol. 2008, Dec 23;6(12):e1.doi:10.1371/journal.pbio.1000001.
- Fellay J, Shianna KV, Ge D, Colombo S, et al, Goldstein DB. A whole-genome association study of major determinants for host control of HIV-1. Science. 2007, Aug 17;317(5840):944-7.
- B.S., Biology, University of California, Los Angeles, CA
- Ph.D., Population Genetics, Stanford University, Stanford, CA
- Director, Institute for Genomic Medicine
- John E. Borne Professor of Genetics and Development Columbia University Medical Center, New York, NY
- The Richard and Pat Johnson Distinguished University Professor, Duke University
- Director, Center for Human Genome Variation, Professor in Molecular Genetics and Microbiology and in Department of Biology, Duke University, Durham, NC.
- Honorary Professor, Institute of Neurology, University College London, UK
- Wolfson Professor of Genetics, University College London, UK
- Honorary Senior Fellow, Institute of Neurology, University College, London, UK
- University Lecturer, University of Oxford, UK