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.

Public Health Relevance

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.

National Institute of Health (NIH)
National Institute of General Medical Sciences (NIGMS)
Research Project (R01)
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Hoodbhoy, Tanya
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Albert Einstein College of Medicine
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Baker, Nicholas E (2017) Patterning the eye: A role for the cell cycle? Dev Biol 430:263-265
Bhattacharya, Abhishek; Li, Ke; Quiquand, Manon et al. (2017) The Notch pathway regulates the Second Mitotic Wave cell cycle independently of bHLH proteins. Dev Biol 431:309-320
Wang, Lan-Hsin; Baker, Nicholas E (2015) Salvador-Warts-Hippo pathway in a developmental checkpoint monitoring helix-loop-helix proteins. Dev Cell 32:191-202
Wang, Lan-Hsin; Baker, Nicholas E (2015) E Proteins and ID Proteins: Helix-Loop-Helix Partners in Development and Disease. Dev Cell 35:269-80
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 (2012) The role of the bHLH protein hairy in morphogenetic furrow progression in the developing Drosophila eye. PLoS One 7:e47503
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
Bhattacharya, Abhishek; Baker, Nicholas E (2011) A network of broadly expressed HLH genes regulates tissue-specific cell fates. Cell 147:881-92
Pennington, M W; Lubensky, D K (2010) Switch and template pattern formation in a discrete reaction-diffusion system inspired by the Drosophila eye. Eur Phys J E Soft Matter 33:129-48

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