Bobby Farboud - Post-Doctoral Scholar
131 Koshland Hall
|Sexual reproduction is pervasive among higher organisms. The decision to become male or female is therefore both fundamental and ubiquitous. Consequently, studies into the mechanism of sex determination have revealed a wealth of information concerning the quantitative molecular signals that determine cell fate, the mechanisms used to maintain cell fate decisions, and the molecular nature of developmental switches. Much of this information has come from studies on the genetically tractable organisms, the fruit fly Drosophila melanogaster and the nematode Caenorhabiditis elegans. C. elegans sexual fate is established by a chromosome counting mechanism that distinguishes one X chromosome from two. This mechanism assesses the number of X chromosomes relative to the sets of autosomes. Genes encoded on the X chromosome, called X signal elements (XSEs), communicate X chromosome dose by functioning in a cumulative, dose-dependent manner to repress the master switch gene xol-1. xol-1 repression in XX embryos results in hermaphrodite development and activation of dosage compensation, the process whereby expression levels of X-linked gene products between XX and XO animals are equalized, despite their difference in X chromosome dose. Autosomal genes called autosomal signal elements (ASE) communicate the autosomal dose and counteract XSEs to activate xol-1 . In XO embryos, XSE dose is insufficient to overcome ASE dose, xol-1 is therefore active, male development ensues, and the dosage compensation machinery is turned off. How XSEs and ASEs oppose each other remains mysterious.
The most potent known XSE, sex-1 , encodes a nuclear hormone receptor that associates with the xol-1 promoter in vivo to repress its transcription. To learn how sex-1 functions and ultimately how XSEs oppose ASEs, I am characterizing the contribution of multiple SEX-1 response elements on the xol-1 promoter, SEX-1 interacting proteins and their roles in sex determination and dosage compensation, and potential SEX-1 ligands.
Farboud, B., Meyer, B.J. (2015) Dramatic Enhancement of Genome Editing by CRISPR/Cas9 Through Improved Guide RNA Design. Genetics February 18, 2015 genetics.115.175166 [PDF]
Farboud, B., Nix, P., Jow, M.M., Gladden, J.M., Meyer, B.J. 2013. Molecular antagonism between X-chromosome and autosome signals determines nematode sex. Genes & Development 27, 1159-1178.
Goodson, M. L., Farboud, B., Privalsky, M. L. 2009. High throughput analysis of nuclear receptor-cofactor interactions. Methods Mol Biol. 505:157-69. PMID: 19117144 [PubMed - indexed for MEDLINE]
Goodson, M. L., Farboud, B., Privalsky, M. L. 2007. An improved high throughput protein-protein interaction assay for nuclear hormone receptors. Nucl. Recept. Signal. Mar 9;5:e002. PMID: 17464356 [PubMed - indexed for MEDLINE]
Gladden, J.M., Farboud, B., Meyer, B.J. 2007. Revisiting the X:A Signal That Specifies Caenorhabditis elegans Sexual Fate. Genetics 177 (3):1639-1654.
Wan, W., B. Farboud, and M. L. Privalsky. 2005. Pituitary resistance to thyroid hormone syndrome is associated with T3 receptor mutants that selectively impair beta2 isoform function. Mol Endocrinol 19:1529-42.
Farboud, B., and M. L. Privalsky. 2004. Retinoic acid receptor alpha is stabilized in a repressive state by its C-terminal, isotype-specific F domain. Mol Endocrinol 18(12):2839-53.
Farboud, B., H. Hauksdottir, Y. Wu, and M. L. Privalsky. 2003. Isotype-restricted corepressor recruitment: a constitutively closed helix 12 conformation in retinoic acid receptors beta and gamma interferes with corepressor recruitment and prevents transcriptional repression. Mol Cell Biol 23:2844-58.
Hauksdottir, H., B. Farboud, and M. L. Privalsky. 2003. Retinoic acid receptors beta and gamma do not repress, but instead activate target gene transcription in both the absence and presence of hormone ligand. Mol Endocrinol 17:373-85.
Sillman, A. L., D. M. Quang, B. Farboud, K. S. Fang, R. Nuccitelli, and R. R. Isseroff. 2003. Human dermal fibroblasts do not exhibit directional migration on collagen I in direct-current electric fields of physiological strength. Exp Dermatol 12:396-402.
Shi, B., B. Farboud, R. Nuccitelli, and R. R. Isseroff. 2003. Power-line frequency electromagnetic fields do not induce changes in phosphorylation, localization, or expression of the 27-kilodalton heat shock protein in human keratinocytes. Environ Health Perspect 111:281-8.
Honda, S., B. Farboud, L. M. Hjelmeland, and J. T. Handa. 2001. Induction of an aging mRNA retinal pigment epithelial cell phenotype by matrix-containing advanced glycation end products in vitro. Invest Ophthalmol Vis Sci 42:2419-25.
Wong, J. W., B. Shi, B. Farboud, M. McClaren, T. Shibamoto, C. E. Cross, and R. R. Isseroff. 2000. Ultraviolet B-mediated phosphorylation of the small heat shock protein HSP27 in human keratinocytes. J Invest Dermatol 115:427-34.
Farboud, B., R. Nuccitelli, I. R. Schwab, and R. R. Isseroff. 2000. DC electric fields induce rapid directional migration in cultured human corneal epithelial cells. Exp Eye Res 70:667-73.
Farboud, B., A. Aotaki-Keen, T. Miyata, L. M. Hjelmeland, and J. T. Handa. 1999. Development of a polyclonal antibody with broad epitope specificity for advanced glycation endproducts and localization of these epitopes in Bruch's membrane of the aging eye. Mol Vis 5:11.
Fang, K. S., B. Farboud, R. Nuccitelli, and R. R. Isseroff. 1998. Migration of human keratinocytes in electric fields requires growth factors and extracellular calcium. J Invest Dermatol 111:751-6.
University of California, Davis
Doctor of Philosophy in Biochemistry and Molecular Biology