David Jay Segal
Assistant Professor
djsegal@ucdavis.edu

Pharmacology - Medicine

Office
4513 GBSF
754-9134


Picture of David Jay Segal
 
Degrees:
1996 PhD Univeristy of Utah Biochemistry
1989 BS Cornell University Biology
Research Interests:

How can we use the information in the human genome to improve human health? Our lab is developing DNA-recognition tools for use in functional genomics and gene therapy. 1) The Cys2-His2 class of zinc fingers are one of natures favorite structural motifs. Our studies try to understand the purpose of these domains, learn how they accomplish their function, then try to use their abilities to create new tools that benefit human health and biological studies. 2) Using the combined approaches of biochemistry, X-ray crystallography, computer modeling, and bioinformatics, we are revealing natures purpose for encoding 4,500 zinc finger domains into our genome. 3) Inhibitors, such as small molecule drugs, could modulate signaling pathways and be useful as therapeutic agents. 4) We can now create custom DNA-binding proteins with enough specificity to bind a unique site in the human genome. 5) By making carefully targeted double-strand breaks in chromosomes, we can engineer insertions, deletions, and genomic rearrangements. For example, we are designing targeted endonuclease to seek and destroy the integrated HIV virus within cells. Other projects aim to repair genetic diseases at the DNA level through targeted homologous recombination. 6) We are developing diagnostic tools, using a process we call SEER (Sequence-Enabled Enzyme Reactivation), that can scan the DNA inside a living cell and produce a signal when a particular sequence is detected.
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.
Department and Center Affiliations:
UC Davis Genome Center
Medical Pharmacology and Toxicology
UC Davis Cancer Center
Center for Biophotonics Science and Technology
California Research Center for the Biology of HIV in Minorities
Professional Societies:
American Society for Gene Therapy
Protein Society
Zinc Finger Consortium
CBS Graduate Group Affiliations:
Biochemistry, Molecular, Cellular and Developmental Biology  
Genetics  
Graduate Groups not Housed in CBS:
Pharmacology and Toxicology  
Publications:
  • 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.
Laboratory Personnel:
4409A GBSF

Mital Bhakta, Kathryn Brayer, Sarah Lockwood, Yuka Shimizu, Artem Zykovich

Courses:
PHA 400 MED: Principles of Pharmacology Fall,Spring
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