Faculty Profile

Dr. Nicholas E. Baker, Ph.D.

Nicholas E. Baker, Ph.D.

Professor, Department of Genetics

Professor, Department of Developmental & Molecular Biology

Professor, Department of Ophthalmology & Visual Sciences

Harold and Muriel Block Chair in Genetics

Areas of Research: Cell-cell signaling during development that controls tissue size and morphology. ‘Cell competition’ that selectively eliminates suboptimal cells from mixed populations of cells growing at different speeds.

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

 

Signaling pathways regulating development, differentiation and growth

 One of the unresolved questions in biology is that of how organs grow.  Extracellular signals are known to play positive and negative roles in cell proliferation and growth, which is also influenced by nutrients, but so far it is not possible to explain how organs measure their size, stop or renew growth, and how growth is coordinated with morphogenesis to determine organ shape.  It is very plausible that cancer as well as degenerative diseases including neurodegenerative diseases reflect defects in these as-yet undefined but fundamental processes.  

In order to uncover and characterize new genes controlling growth, our group uses genetics to identify and study mutations with growth defects in Drosophila melanogaster.  Our current research addresses the following new mechanisms of growth regulation:  1) the relationship between cell fate and cell proliferation, and how cell determination genes control the cell cycle, especially during development of the nervous system; 2) new mechanisms by which ribosomes regulate growth; 3) cell competition, which is a way growing tissues respond to the presence of cells with different growth properties.  

The approaches used include mutagenesis studies to identify new regulators of neural development, incorporating whole genome sequencing and novel mapping methods for mutant identification, physical biochemical studies of protein dimerization in vitro, methods to detect specific protein dimers in vivo, and developmental genetic analysis of gene function in vivo. 

1)  The proneural bHLH proteins are the master regulators for most neuronal differentiation.  These transcription factors also coordinate the cell cycle behavior.  Defects in bHLH expression activate the Hippo pathway of tumor suppressors and eliminate progenitor cells.  Current projects include how the dimerization choices of different HLH proteins control differentiation and growth, new evidence that protein stability is important, and how HLH proteins and the Hippo pathway also affect Wnt signaling.  Aspects of these studies are potentially relevant to schizophrenia, which is linked to certain bHLH proteins, possibly through control of dendrite morphogenesis. 

2)  Ribosomes are, of course, essential for growth because they are essential for protein synthesis.  Our group has discovered surprising novel signaling pathways activated by defects in ribosome assembly.  These signals may play the major role in the growth defects that result, more than any direct effects on translation.  These signaling pathways may explain the symptoms of different human ribosomopathies and may underlie the evidence that ribosomal protein genes can be tumor suppressors, since they are unexpectedly mutated in multiple human tumors.  We will be undertaking molecular studies of transcription and other mechanisms of gene regulation in the Drosophila pathways, and exploring the function of their mouse counterparts in novel growth-regulatory pathways.           

 3)  An emerging aspect of organ growth is ‘cell competition’.  When organs contain cells growing at different speeds, cell competition can causes selective apoptosis of the out-competed cells only when they are close to the competing cell type.  Even normal cells can be out-competed, for example if they are exposed to cells with an extra gene copy of the proto-oncogene Myc.  Cell competition is thought to select for the fittest progenitor cells during organ growth and eliminate defective cells.  Cell competition is suggested to play positive or negative roles in cancer development and may be a factor in the success of stem cell transplantation and regenerative therapies.  Our lab is studying how differences in growth lead to cell competition, and its consequences for the detection and removal of cells with damaged DNA following irradiation and during aging, and plans to characterize the role of cell competition in mammals.

For more details, and complete list of publications, please see our website at
http://fruitfly4.aecom.yu.edu/index.html

Selected Publications

 

Selected recent publications  

Baker, N.E.  (2017)  Patterning the eye: a role for the cell cycle?  Dev. Biol.  [Epub ahead of print].  PMID: 28733162

Baker, N.E.  (2017) Mechanisms of cell competition emerging from Drosophila studies Curr Opin Cell Biol  48: 40-46. PMID: 28600967

Lee, C.-H., Rimesso, G., Reynolds, D., Cai, J. and Baker, N.E.  (2016) Whole genome sequencing and iPLEX MassARRAY genotyping map an EMS-induced mutation affecting cell competition in Drosophila melanogaster.  G3(Bethesda) 6: 3207-3217. PMID: 27574103

Baker, N.E. and Kale, A. (2016).  Ribosomal protein mutations: apoptosis, cell competition and cancer.  Mol Cell Oncol 3:1, e1029065. PMID: 27308545

Wang, L.-H. and Baker, N.E. (2015) E-proteins and Id-proteins: helix-loop-helix partners in development and disease.  Dev Cell 35: 269-280.  PMID: 26555048

Kale, A., Li, W., Lee, C.-H. and Baker, N.E (2015)  Apoptotic mechanisms during competition of ribosomal protein mutant cells: roles of the initiator caspases Dronc and Dream/Strica. Cell Death Different 22:1300-1312. PMID: 25613379

Wang, L.-H. and Baker, N.E.  (2015) Salvador-Warts-Hippo pathway in a developmental checkpoint monitoring Helix-Loop-Helix proteins.  Dev Cell 32:191-202. PMID: 25579975

Ruggiero, R., Kale, A., Thomas, B.J., and Baker, N.E.  (2012)  Mitosis in neurons: Roughex and APC/C maintain cell cycle exit to prevent cytokinetic and axonal defects in Drosophila photoreceptor neurons. PLoS Genet.  8:  e1003049.  PMID: 23209426

Bhattacharya, A., and Baker, N.E.  (2011)  A network of broadly-expressed HLH genes regulates tissue-specific cell fates.  Cell 147: 881-892. PMID: 22078884

More Information About Dr. Nicholas Baker

Baker laboratory

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

Tel: 718.430.2854

Research Information

In the News

USA Today quotes Dr. Nicholas Baker about a recent paper in Nature that found a gene which may be responsible for the color and patterns that appear on insect wings.

More media coverage