Goldstein Lab

Location and Contact Information

Dr. David Goldstein's Lab
630 West 168th Street
P&S 11-401 and 11-453
New York, NY 10032
United States

Research Summary

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.

Current Projects

  • 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


  • Epi4K Consortium
  • Epilepsy Genetics Initiative
  • Epi25
  • 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

Lab Members

Current Members

  • Irina Lebedeva, PhD

    Associate Research Scientist (Lab Manager)

  • Anna Alkelai, PhD

    Postdoctoral Research Scientist

  • Evan Baugh, PhD

    Postdoctoral Research Scientist

  • Sophie Colombo

    Associate Research Scientist

  • Ryan Dhindsa

    Graduate Student

  • Sarah Dugger

    Graduate Student

  • Sahar Gelfman, PhD

    Associate Research Scientist

  • Tristan Hyaek, PhD

    Postdoctoral Scholar

  • Daniel Krizay

    Graduate Student

  • Gino Montero


  • Neha Raghavan, PhD

    Postdoctoral Research Scientist

  • Andrew Ressler

    Graduate Student

  • Patrick Shea, PhD

    Associate Research Scientist

  • Xinchen Wang, PhD

    Postdoctoral Research Scientist

  • Charles Wolok

    Staff Associate

Select Publications

  • 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.