David Segal

image of David Segal

Professor

Departments

Biochemistry and Molecular Medicine
Pharmacology - Medicine
MIND Institute - UCD Medical Center
UC Davis Genome Center

Offices and Labs

4512 GBSF
754-9134

Profile Introduction

Zinc finger, TALE, CRISPR/Cas genome engineering and targeted gene regulation for applications in research and therapeutics, especially neurologic disorders.

Degrees

1996 PhD Biochemistry Univeristy of Utah
1989 BS Biology Cornell University

Research Interests

Genome and Epigenome Editing for the Study and Treatment of Disease

Almost every disease has a genetic component. Often this information is used only to determine how condemned a person is to develop disease. We would like to use the genetic information to fix the disease. A guiding principle for our work has been to study how nature does what it does, then attempt to use that knowledge to make useful tools to improve public health, either through increased knowledge or therapeutic intervention. Projects in the Segal Lab revolve around engineering zinc finger, TALE, or CRISPR DNA-binding proteins for specific applications. • Genetic variation and human diseases: Functional analysis of GWAS SNPs by gene editing, 4C, single cell analyses • Gene therapy: epigenetic therapy for Angelman Syndromes and other brain disorders • ZFNs, TALENs and CRISPRs: targeted nucleases, transposases, transcription factors. 

Zinc finger, TALE, CRISPR/Cas genome engineering and targeted gene regulation for applications in research and therapeutics, especially neurologic disorders.

Awards

2011 W.M. Keck Foundation Medical Research Award

Department and Center Affiliations

UC Davis Genome Center
UC Davis Cancer Center

ProfessionalSocieties

American Society for Gene Therapy
American Society of Human Genetics

CBS Grad Group Affiliations

Biochemistry, Molecular, Cellular and Developmental Biology
Integrated Genetics and Genomics
Molecular, Cellular, and Integrative Physiology

Specialties / Focus

Integrated Genetics and Genomics
  • Chromosome Biology
  • Human Genetics and Genomics
Biochemistry, Molecular, Cellular and Developmental Biology
  • Molecular Medicine
  • Chromosome Dynamics and Nuclear Function
  • Genomics, Proteomics and Metabolomics
Molecular, Cellular, and Integrative Physiology
  • Molecular Physiology

Graduate Groups not Housed in CBS

Pharmacology and Toxicology

Labs

4617A GBSF website
  • Dr. Henny O'Geen
  • Ben Pyles
  • Nicole Coggins (MCIP)
  • Jesse Lopez (IGG)
  • Peter Deng (PTX)
  • Kevin De Leon (MCIP)

Courses

• FRS 001 Fresh Sem: Gene Therapy - How Genes Control You and How You Can Controll Them (Fall)
• PHA 250 Functional Genomics: From Bench To Bedside (Spring)
• GGG 201A Advanced Genetic Analysis (Fall)
• MCB 211 Macromolecular Structure & Interactions (Fall)

Publications

10/2/2016 11:42:54 AM
  • Bailus, B.J., Pyles, B., McAlister, M.M., O’Geen, H., Lockwood, S.H., Adams, A.A., Trang Nguyen J.T., Berman R.F., and Segal, D.J. (2016) Protein Delivery of an Artificial Transcription Factor Restores Widespread Ube3a Expression in an Angelman Syndrome Mouse Brain. Mol Ther. 24:548-555.

  • Fink KD, Deng P, Gutierrez J, Anderson JS, Torrest A, Komarla A., Kalomoiris S, Cary W, Anderson JD, Gruenloh W, Duffy A, Tempkin T, Wheelock V, Segal DJ, and Nolta, JA. Allele-specific reduction of the mutant huntingtin allele using transcription activator-like effectors in human Huntington’s disease fibroblasts. Cell Transplant. 25:677-686.

  • Tak, Y.G., Hung, Y., Yao, L., Grimmer, M.R., Do, A., Bhakta, M.S., O'Geen, H., Segal, D.J., Farnham, P.J. (2016) Effects on the transcriptome upon deletion of distal elements are not correlated with the size of H3K27Ac peaks in human cells. Nucleic Acids Res. pii: gkv1530.

  • O’Geen, H., Yu, A.S., and Segal, D.J. How specific is CRISPR/Cas9 really? (2015) Current Opinions in Chemical Biology. 29:72–78.

  • O'Geen, H., Henry, I.M., Bhakta, M.S., Meckler, J.F., Segal, D.J. (2015) A genome-wide analysis of Cas9 binding specificity using ChIP-seq and targeted sequence capture. Nucleic Acids Res. 43:3389-3404.

  • Bailus, B.J., Segal, D.J. (2014) The Prospect of Molecular Therapy for Angelman Syndrome and Other Autism Spectrum Disorders. BMC Neurosci, 15:76.

  • Lockwood, S.H., Guan, A., Yu, A.S., Zhang, C., Zykovich, A., Korf, I., Rannala, B., Segal, D.J. (2014) The Functional Significance of Common Polymorphisms in Zinc Finger Transcription Factors. G3, pii: g3.114.012195.

  • Barrilleaux, B., Burow, D., Lockwood, S., Yu, A., Segal, D.J., Knoepfler, P. (2014) Miz-1 activates gene expression via a novel consensus DNA binding motif. PLoS One. 9:e101151.

  • Johnson, L.M., Du, J., Hale, C.J., Bischof, S, Feng, S., Chodavarapu, R.K., Zhong, X., Marson, G., Pellegrini, M., Segal, D.J., Patel, D.J., Jacobsen, S.E. (2014) SRA/SET domain-containing proteins link RNA polymerase V occupancy to DNA methylation. Nature, 507:124-128.

  • Bailus, B.J., Segal, D.J. (2014) The Prospect of Molecular Therapy for Angelman Syndrome and Other Autism Spectrum Disorders. BMC Neurosci, 15:76.

  • Lockwood, S.H., Guan, A., Yu, A.S., Zhang, C., Zykovich, A., Korf, I., Rannala, B., Segal, D.J. (2014) The Functional Significance of Common Polymorphisms in Zinc Finger Transcription Factors. G3, pii: g3.114.012195.

  • Segal, D.J. and Meckler, J.F., (2013) Genome Engineering at the Dawn of the Golden Age, Annu. Rev. Genomics Hum. Genet, 14:135–158.
  • Meckler, J.F., Bhakta, M.S., Kim, M-S., Ovadia, R., Habrian, C.H., Zykovich, A., Yu, A., Lockwood, S.H., Morbitzer, R., Elsäesser, J., Lahaye, T., Segal, D.J., and Baldwin, E.P. (2013) Quantitative Analysis of TALE-DNA Interactions Suggests Polarity Effects, Nucleic Acids Res, 41:4118-4128.
  • Bhakta, M.S., Henry, I.M., Ousterout, D.G., Theva Das, K., Lockwood, S.H., Meckler, J.F., Wallen, M.C., Zykovich, As, Yu, Y., Leo, H., Xu, L., Gersbach, C.A. and Segal, D.J. (2013) Highly Active Zinc-Finger Nucleases by Extended Modular Assembly, Genome Research, 23:530-538.
  • Owens, J.B., Mauro, D., Stoytchev, I., Bhakta, M.S., Kim, M.-S., Segal, D.J. and Moisyadi, S. (2013) Transcription activator like effector (TALE) directed piggyBac transposition in human cells. Nucleic Acids Res, 41:9197-9207.

  • Meier, J.L., Yu, A., Korf, I., Segal, D.J. and Dervan, P.B. (2012) Guiding the Design of Synthetic DNA-Binding Molecules with Massively Parallel Sequencing, J Am Chem Soc. 134:17814-17822.
  • Zykovich, A., Korf, I. and Segal, D.J. (2009) Bind-n-Seq: high-throughput analysis of in vitro protein-DNA interactions using massively parallel sequencing. Nucleic Acids Res. 37:e151.
  • Kim, M.-S., Stybayeva, G., Lee, J.Y., Revzin, A., and Segal, D.J. (2011) A zinc finger protein array for the visual detection of pathogen-specific DNA sequences. Nucleic Acids Res. 39:e29.
  • Shimizu, Y., Şöllü, C., Meckler, J. M., Adriaenssens, A., Zykovich, A., Cathomen, T., and Segal, D.J. (2011) Adding Fingers To An Engineered Zinc Finger Nuclease Can Reduce Activity. Biochemistry, 50:5033-5041
  • Mackay, J.P., Font, J., and Segal, D.J. (2011) The prospects for designer single-stranded RNA-binding proteins. Nature Struct Mol Biol, 18:256-261
  • Furman, J. L., Badran, A. H., Ajulo, O., Porter, J. R., Stains, C. I., Segal, D. J., and Ghosh, I. (2010) Toward a General Approach for RNA-Templated Hierarchical Assembly of Split-Proteins, J Am Chem Soc. 132:11692-11701.
  • Szczepek, M., Brondani, V., Büchel, J., Serrano, L., Segal, D.J. and Cathomen, T. (2007) Structure-based redesign of the dimerization interface reduces the toxicity of zinc finger nucleases. Nat. Biotechnol., 25:786-793.
  • Alwin, S., Gere, M. B., Guhl, E., Effertz, K., Barbas, C. F., 3rd, Segal, D. J., Weitzman, M. D., and Cathomen, T. (2005). Custom Zinc-Finger Nucleases for Use in Human Cells. Mol Ther.
  • Carroll, D., Morton, J.J., Beumer, K.J. & Segal, D.J. (2006) Construction and Testing of Zinc Finger Nucleases. Nat. Protocols, 1:1329-1341.