Degrees:
1996
PhD
Univeristy of Utah
Biochemistry
1989
BS
Cornell University
Biology
Research Interests:
• Engineered DNA-binding proteins as therapeutics and molecular tools for genomics.
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. Specific research foci in the Segal Lab revolve around engineering custom zinc finger DNA-binding proteins for specific applications. We also continue to make methodological improvements, many of which have been widely adapted in the field.
Specific research foci in the Segal Lab revolve around engineering custom DNA-binding proteins for the following applications:
• Genetic variation and human diseases: SNP functions in Coronary Artery Disease
• Gene therapy: epigenetic therapy for Angelman and Rett Syndromes
• Gene therapy: permanent disruptors of the HIV genome
• Zinc finger and TAL effector proteins: targeted nucleases, transposases, transcription factors.
• Biology of human zinc finger transcription factors: role of genetic variation
• Probes and diagnostic tools of genetic and epigenetic information
http://http://www.genomecenter.ucdavis.edu/segallab/segal-lab-page
Structure/function of DNA-binding proteins and their application in functional genomics and gene therapy; protein engineering of sequence-specific therapeutics and molecular tools that can modify target genes in the human genome.
Awards:
2011 W.M. Keck Foundation Medical Research Award
Department and Center Affiliations:
UC Davis Genome Center
UC Davis Cancer Center
Professional Societies:
American Society for Gene Therapy
American Society of Human Genetics
CBS Graduate Group Affiliations:
Biochemistry, Molecular, Cellular and Developmental Biology
Genetics
Specialties / Focus:
Biochemistry, Molecular, Cellular and Developmental Biology
Chromosome Dynamics and Nuclear Function
Genomics, Proteomics and Metabolomics
Molecular Medicine
Structural and Mechanistic Biochemistry
Genetics
Chromosome Biology
Human Genetics
Graduate Groups not Housed in CBS:
Pharmacology and Toxicology
Publications:
Last updated 2/25/2012
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.
Carroll, D., Morton, J.J., Beumer, K.J. & Segal, D.J. (2006) Construction and Testing of Zinc Finger Nucleases. Nat. Protocols, 1:1329-1341.
Ghosh, I., Stains, C.I., Ooi, A.T., & Segal, D.J. (2006) Direct detection of double-stranded DNA: molecular methods and applications for DNA diagnostics. Mol. BioSystems, 2:551-560.
Segal, D.J.*, Crotty, J., Bhakta, M., Barbas III, C.F., & Horton, N.C.* (2006) Structure of Aart, a Designed Six-Finger Zinc Finger Peptide, bound to DNA. J. Mol. Biol, 363:405-412.
Ooi, A.T., Stains, C.I., Ghosh, I., & Segal, D.J. (2006) SEquence-Enabled Reassembly of ?-Lactamase (SEER-LAC): a Sensitive Method for the Detection of Double-Stranded DNA. Biochemistry, 45:3620-3625.
Stains, C. I., Porter, J. R., Ooi, A. T., Segal, D. J., and Ghosh, I. (2005). DNA sequence-enabled reassembly of the green fluorescent protein. J Am Chem Soc 127, 10782-10783.
Kolb, A. F., Coates, C. J., Kaminski, J. M., Summers, J. B., Miller, A. D., and Segal, D. J. (2005). Site-directed genome modification: nucleic acid and protein modules for targeted integration and gene correction. Trends Biotechnol 23, 399-406.
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.
Coates, C. J., Kaminski, J. M., Summers, J. B., Segal, D. J., Miller, A. D., and Kolb, A. F. (2005). Site-directed genome modification: derivatives of DNA-modifying enzymes as targeting tools. Trends Biotechnol 23, 407-419.
Tan, W., Zhu, K., Segal, D. J., Barbas, C. F., 3rd, and Chow, S. A. (2004). Fusion proteins consisting of human immunodeficiency virus type 1 integrase and the designed polydactyl zinc finger protein E2C direct integration of viral DNA into specific sites. J Virol 78, 1301-1313.
Segal, D. J., Goncalves, J., Eberhardy, S., Swan, C. H., Torbett, B. E., Li, X., and Barbas, C. F., 3rd (2004). Attenuation of HIV-1 replication in primary human cells with a designed zinc finger transcription factor. J Biol Chem 279, 14509-14519.
Blancafort, P., Segal, D. J., and Barbas, C. F., 3rd (2004). Designing transcription factor architectures for drug discovery. Mol Pharmacol 66, 1361-1371.
Segal, D. J. (2002). The use of zinc finger peptides to study the role of specific factor binding sites in the chromatin environment. Methods 26, 76-83.
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.
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.
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.
Segal, D.J. (2011) Zinc-finger nucleases transition to the CoDA. Nat Methods. 8:53-55.
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
Laboratory Personnel:
4409A GBSF
http://www.genomecenter.ucdavis.edu/segallab
Mital Bhakta
Sarah Lockwood (BMCDB)
Barbara Bailus (GGG)
Kumitaa Theva Das (GGG)
Joshua Meckler (BMCDB)
Abigail Yu (GGG)
Scot Lieser
Ben Pyles
Alexa Adams
Jennifer Trang Nguyen
Courses:
FRS
001
Fresh Sem: Gene Therapy - How Genes Control You and How You Can Controll Them
Fall,Spring
PHA
250
Functional Genomics: From Bench To Bedside
Spring
Gene Ther
PHA 225
Gene Therapy
Spring
•
PHA 225
Gene Therapy
Spring
•
GGG 201C
Molecular Genetics of Disease
Spring
•
BCM 410A
Molecular Medicine
Fall
•
MCB 211
Macromolecular Structure & Interactions
Fall