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Nicholas E. Baker, Ph.D.

Nicholas E. Baker, Ph.D.

Professor, Department of Developmental & Molecular Biology

Professor, Department of Ophthalmology & Visual Sciences

Harold and Muriel Block Chair in Genetics

Director, Department of Genetics Division of Molecular Genetics

Area of Research: 'Cell competition' that selectively eliminates suboptimal cells from mixed populations of cells growing at different speeds. Proneural bHLH transcription factors and neural cell fate.

Contact Information

718.430.2854

Albert Einstein College of Medicine
Jack and Pearl Resnick Campus
1300 Morris Park Avenue
Ullmann Building, Room 805
Bronx, NY 10461

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Professional Interests

Nicholas E. Baker, PhD
PhD 1986 MRC Laboratory of Molecular Biology, Cambridge UK
Postdoc HHMI & Department of Molecular Cell Biology, UC Berkeley
Albert Einstein College of Medicine 1991-present

Genes that control cell competition, translation, and neuronal development

Genetic studies can be used to uncover new genes and to characterize their roles in vivo. Our current research uses both Drosophila and mice to address newly discovered mechanisms of growth regulation. These involve the mechanisms and functions of ‘cell competition’ in development and pathology, the regulation of ribosome biogenesis and translation, and the regulation of neural cell fate and reprogramming by transcription factors.

Cell competition When organs contain mixed genotypes, for example because of somatic mutation during aging, ‘cell competition’ can result. Our studies show that cell competition is the mechanism that selectively removes cells that have become aneuploid, or acquired other large-scale genetic changes. Since aneuploidy is found in nearly all cancers, is a hallmark of aging, and is responsible for birth defects and most spontaneous miscarriage, cell competition may be important in preventing cancer, birth defects and age-related diseases. Our current goals include the molecular characterization of the cell competition pathway using Drosophila and exploring its roles in aneuploidy cancer and aging in mice.

Regulation of translation Ribosomes are essential for growth. Their biogenesis and assembly are regulated, both during growth and in neurodegenerative disease. Our laboratory has discovered that cell competition involves novel signaling pathways that are activated by defects in ribosome assembly. Ribosomal proteins are affected in several human diseases and also appear to act as tumor suppressors for multiple cancers. How ribosomal proteins act as tumor suppressors is not yet clear or affect neurological disease is not yet clear. We are interested in the molecular signaling mechanisms activated by ribosomes, and their potential roles in mammalian diseases.

Neural cell fate determination Proneural bHLH proteins are the transcriptional master regulators for most neuronal differentiation and important in neuronal reprogramming strategies. Their activities appear to be highly regulated. Our studies use genetic screening in Drosophila, modern genome resequencing methods and multidisciplinary studies to characterize how proneural bHLH proteins are regulated in neuronal fate determination. Surprisingly, defects in proneural bHLH genes act in part through non-apoptotic caspase-dependent processes that appear to control neuronal cell fate specification. Homologs of many of these genes are implicated in schizophrenia, axon and dendrite patterning, suggesting that transcriptional control of non-apoptotic caspase signaling may be relevant to brain diseases.

Also please see our website at http://www.einstein.yu.edu/labs/bakerlab/

Selected Publications

1. Ji, Z., Chuen, J., Kiparaki, M. and Baker, N.E. (2021) Cell competition removes aneuploid cells from Drosophila imaginal discs based on ribosomal protein gene dose. Elife, in press

2. Quiquand, M., Rimesso, G., Qiao, N., Suo, S., Zhou, C., Slattery, M., White, K.P., Han, J.J., and Baker, N.E. (2021) New regulators of Drosophila eye development identified from temporal transcriptome changes Genetics, in press.
doi: 10.1093/genetics/iyab007

3. Baker, N.E. (2020) Emerging mechanisms of cell competition. Nature Reviews Genetics, 21:683-697.

4. Blanco, J., Cooper, J.C., and Baker, N.E. (2020) Roles of C/EBP class bZip proteins in the growth and cell competition of Rp (“Minute”) mutants in Drosophila (2020). Elife, 9 9:e50535.

5. Ji, Z., Kiparaki, M., Folgado, V., Kumar, A., Blanco, J. Rimesso, G., Liu, Y., Zheng, D., and Baker, N.E. (2019) Drosophila RpS12 controls translation, growth, and cell competition through Xrp1. PLoS Genetics, 15(12):e1008513.

6. Wang, L.-H. and Baker, N.E. (2019) Salvador-Warts-Hippo pathway regulates sensory organ development via caspase-dependent non-apoptotic signaling. Cell Death & Disease 10 669.

7. Li, K. and Baker, N.E. (2019) Transcriptional and post-transcriptional regulation of extra macrochaetae during Drosophila adult peripheral neurogenesis. Dev Biol 449: 41-51.

8. Baker, N.E., Kiparaki, M., and Khan, C. (2019) A potential link between p53, cell competition and ribosomopathy in mammals and in Drosophila. Dev Biol 446: 17-19.

9. Lee, C.H., Kiparaki, M., Blanco, J., Folgado, V., Ji, Z., Kumar, A., Rimesso, G., and Baker, N.E. (2018) A regulatory response to ribosomal protein mutations controls translation, growth, and cell competition. Dev Cell, 46, 456-469.

10. Baker, N.E., and Brown, N.L. (2018) All in the family: neuronal diversity and proneural bHLH genes. Development, 145: dev159426.

11. Li, K., and Baker, N.E. (2018) Regulation of the Drosophila ID protein Extra Macrochaetae by proneural dimerization partners. Elife 7: e33967.

12. Kale, A., Ji, Z., Kiparaki, M., Rimesso, G., Flibotte, S., and Baker, N.E. (2018) Ribosomal protein S12e has a distinct function in cell competition. Dev Cell 44, 42-55.

13. Baker, N.E. (2017) Mechanisms of cell competition emerging from Drosophila studies. Curr Opin Cell Biol 48, 40-46.

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Nicholas E. Baker, Ph.D.

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