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
Regulatory genes that control translation, cell competition, and neuronal development
One of the unresolved questions in biology is that of how organs grow. It is thought that cancer and neurodegenerative diseases involve defects in the regulation of cell growth and survival that are fundamental to organ growth.
Genetic studies can be used to uncover new genes controlling tissue growth and maintenance, 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 cell genotypes, for example because of somatic mutation during aging, ‘cell competition’ can eliminate less fit cells through selective apoptosis of only these cells. Our studies show that cell competition is a mechanism that can remove cells that have become aneuploid, or acquired other large-scale genetic changes, and may be important in preventing birth defects and cancer. Our current goals include the molecular characterization of the cell competition pathway using Drosophila and its conservation and roles in aneuploidy cancer and aging in mice.
Regulation of ribosome biogenesis Ribosomes are essential for growth. Their biogenesis and assembly are regulated, both during growth and in neurodegenerative disease. Our laboratory has discovered novel signaling pathways that are activated when defects occur in ribosome assembly, and that also affect cell competition (see above). 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 studying the molecular signaling mechanisms activated by ribosomes, and their potential roles in mammalian diseases such as Diffuse Large B-Cell Lymphoma (DLBCL).
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 reseqeuncing methods and multidisciplinary studies to characterize how proneural bHLH proteins are regulated in neuronal development.
Also please see our website at http://www.einstein.yu.edu/labs/bakerlab/