The goal of this project is to identify the mechanisms by which transcription factors of the Helix-loop-helix class control proliferation and differentiaton during development, and to identify mechanisms that might be used to influence such proteins in diseases. Studies of eye development in Drosophila melanogaster have identified a conserved common mechanism that regulates photoreceptor cell differentiation and also functions in many other organs. The molecular mechanisms that regulate helix-loop-helix proteins in the eye and other tissues will be elucidated through molecular genetic studies of transcriptional, post-transcriptional, and post-translational regulation. The connection between differentiation and cell proliferation and survival will be elucidated from studies of the regulatin of tumor suppressor genes by helix-loop-helix transcription factors. Genetic screens will be conducted that will identify other components of the process, and seek to identify novel molecular mechanisms by which disease processes can be influenced.
A small family of related transcription factors has been found to regulate cell proliferation and cell differentiation in a large number of tissues. Defects in thse proteins occur in multiple diseases including cancer, schizophrenia, diabetes, and eye diseases. This project investigates the properties of these proteins, with the ultimate goal of influencing their function to treat and prevent disease.
|Baker, Nicholas E; Li, Ke; Quiquand, Manon et al. (2014) Eye development. Methods 68:252-9|
|Baker, Nicholas E (2013) Developmental regulation of nucleolus size during Drosophila eye differentiation. PLoS One 8:e58266|
|Bhattacharya, Abhishek; Baker, Nicholas E (2011) A network of broadly expressed HLH genes regulates tissue-specific cell fates. Cell 147:881-92|
|Baker, Nicholas E; Firth, Lucy C (2011) Retinal determination genes function along with cell-cell signals to regulate Drosophila eye development: examples of multi-layered regulation by master regulators. Bioessays 33:538-46|
|Lubensky, David K; Pennington, Matthew W; Shraiman, Boris I et al. (2011) A dynamical model of ommatidial crystal formation. Proc Natl Acad Sci U S A 108:11145-50|
|Firth, Lucy C; Bhattacharya, Abhishek; Baker, Nicholas E (2010) Cell cycle arrest by a gradient of Dpp signaling during Drosophila eye development. BMC Dev Biol 10:28|
|Bhattacharya, Abhishek; Baker, Nicholas E (2009) The HLH protein Extramacrochaetae is required for R7 cell and cone cell fates in the Drosophila eye. Dev Biol 327:288-300|
|Baker, Nicholas E; Bhattacharya, Abhishek; Firth, Lucy C (2009) Regulation of Hh signal transduction as Drosophila eye differentiation progresses. Dev Biol 335:356-66|
|Firth, Lucy C; Baker, Nicholas E (2009) Retinal determination genes as targets and possible effectors of extracellular signals. Dev Biol 327:366-75|
|Firth, Lucy C; Baker, Nicholas E (2007) Spitz from the retina regulates genes transcribed in the second mitotic wave, peripodial epithelium, glia and plasmatocytes of the Drosophila eye imaginal disc. Dev Biol 307:521-38|
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