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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. Novel physiological effects of ribosomal protein mutations. Proneural bHLH transcription factors and neural cell fate.

Contact Information

718.430.2854nicholas.baker@einsteinmed.org

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

Cell competition, translation, and neuronal development

One of the most effective ways to find the genes required for a poorly-understood process is the genetic approach of identifying mutations that disrupt the process. We use Drosophila and more recently mice to address newly discovered mechanisms of growth regulation and of neural development.

Cell competition and aneuploidy Competition can occur between cells that differ from one another in developing tissues. We discovered that a specific pathway of cell competition selectively removes cells that have become aneuploid, or acquired other large-scale genetic changes. Aneuploidy, ie the gain or loss of whole chromosomes, is found in almost all cancers, and mouse models that increase aneuploidy increase tumor incidence and promote aging, so that a process recognizing and removing aneuploid cells is likely to be tumor suppressive and to support more healthy aging. Using fruitflies to identify genes that are required for cell competition, we have begun to identify the molecular pathways involved. Our current goals include the molecular mechanisms of the cell competition pathway, including how differences between cells are recognized, how cell competition and the tumor suppressor p53 are related, and how changes in cell competition might increase or be exploited to decrease cancer incidence, both in fruitflies and in mammals.

Regulation of translation Ribosomes are essential for growth. Their biogenesis and assembly are regulated, both during growth and in neurodegenerative disease. 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. Our laboratory discovered that defects in ribosome assembly surprisingly cause transcriptional responses. We are interested in the molecular signaling mechanisms activated by ribosomes, and their potential roles in cancer and neurological 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.

Some recent commentaries on our lab's research:

Nature Reviews Genetics | https://doi.org/10.1038/s41576-021-00373-5

https://elifesciences.org/digests/61172/neighborhood-watch

https://elifesciences.org/articles/53348

Also please see our website at https://einsteinmed.org/labs/bakerlab/

Selected Publications

1. Kiparaki, M., Khan, C., Folgado-Marco, V., Chuen, J., and Baker, N.E. The transcription factor Xrp1 orchestrates both reduced translation and cell competition upon defective ribosome assembly or function. BioRxiv preprint https://doi.org/10.1101/2021.07.12.452023

2. Folgado-Marco, V., Ames, K., Chuen, J., Gritsman, K., and Baker, N.E. Haploinsufficiency of the essential gene RpS12 causes defects in erythropoiesis and hematopoietic stem cell maintenance. BioRxiv preprint https://doi.org/10.1101/2021.05.04.442585

3. 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, 10; e61172.

4. 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, doi: 10.1093/genetics/iyab007

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

6. 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.

7. 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.

8. 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.

9. 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.

10. 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.

11. 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.

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

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

13. 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.

14. 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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Research Brief

Cell Competition Eliminates Abnormal Cells

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