Professor Emeritus of Neurobiology*
*Coates Family Professor of Neuroscience, Helen Wills Neuroscience Institute; Director, QB3 Functional Genomics Laboratory
Our lab is interested in understanding the molecular and cellular mechanisms underlying the function, development and regeneration of the vertebrate olfactory system. We use a wide range of experimental tools and model systems, including molecular biology, genomics, computational biology and behavior to study these processes using the mouse and zebrafish as model systems. We are also developing genomics and genome engineering technologies to characterize the neuronal diversity in the cerebral cortex and other regions of the nervous system.
Olfactory Stem Cells and Neural Regeneration. In the vertebrate olfactory system, primary sensory neurons are continuously regenerated throughout adult life via the proliferation and differentiation of multipotent neural progenitor cells. This feature makes the olfactory system particularly amenable for studies on adult neurogenesis and the properties of neuronal stem cells. Olfactory sensory neurons normally turn over every 30-60 days and are replaced through the proliferation and differentiation of multipotent progenitor cells. Following injury that results in the destruction of mature cells in the olfactory epithelium, these adult tissue stem cells proliferate and differentiate to reconstitute all cellular constituents of this sensory epithelium. The regenerative capacity of the olfactory epithelium represents a powerful and experimentally accessible paradigm for understanding the regulation of neural stem cell function under normal conditions and during injury-induced regeneration. While distinct stages of the olfactory lineage have been identified, however, much remains to be learned about the genetic programs that both define and regulate olfactory neurogenesis during development and regeneration. Current projects are using a variety of approaches – including targeted gene knockouts to assess the function of transcription factors and stem cell factors, and single cell RNA sequencing – to elucidate the molecular and cellular mechanisms regulating olfactory stem cells and olfactory neurogenesis in the mouse. Our studies provide a model for understanding the mechanisms regulating adult neural stem cells and lay the groundwork for the future development of treatments and therapeutics to ameliorate tissue damage and degeneration in the nervous system.
The Ngai Lab BRAIN Initiative Project: Cell Type Classification in the Brain. A major goal of neuroscience is to understand how circuits of neurons and non-neuronal cells process sensory information, generate movement, and subserve memory, emotion and cognition. Elucidating the properties of neural circuits requires an understanding of the cell types that comprise these circuits and their roles in processing and integrating information. However, since the description of diverse neuronal cell types over a century ago by Ramon y Cajal, we have barely scratched the surface of understanding the diversity of cell types in the brain and how each individual cell type contributes to nervous system function. Historical approaches for classifying neurons rely upon features including the differential expression of small numbers of genes, cell morphology, anatomical location, physiology, and connectivity – important descriptive properties that nonetheless are insufficient to fully describe or predict the vast number of different cell types that comprise the mammalian brain. This NIH-supported BRAIN Initiative project – a collaboration between the Ngai lab and 4 other research groups at UC Berkeley and part of the larger BRAIN Initiative Cell Census Network – is focused on developing single cell RNA sequencing approaches for identifying and classifying the diverse cell types in the mammalian nervous system and CRISPR/Cas9 gene editing techniques for genetically targeting newly discovered cell types.
Brunet, L.J., G.H. Gold, and J. Ngai. 1996. General anosmia caused by a targeted disruption of the mouse olfactory cyclic nucleotide-gated cation channel. Neuron 17, 681-693. PMID: 8893025
Barth, A.L., J.C. Dugas, and J. Ngai. 1997. Noncoordinate expression of odorant receptor genes tightly linked in the zebrafish genome. Neuron 19, 359-369. PMID: 9292725
Lin, D.M., F. Wang, G. Lowe, G. H. Gold, R. Axel, J. Ngai, and L. Brunet. 2000. Formation of precise synaptic connections in the olfactory bulb occurs in the absence of odorant-evoked neuronal activity. Neuron 26, 69-80. PMID: 10798393
Duggan, C.D., S. DeMaria, A. Baudhuin, D. Stafford, and J. Ngai. 2008. Foxg1 is required for development of the vertebrate olfactory system. J. Neurosci. 28, 5229-5239. PMID: 18480279 PMCID: PMC2706027
Scolnick, J.A., K. Cui, S. Xuan, C.D. Duggan, X.-b Yuan, A. Efstratiadis, and J. Ngai. 2008. Role of IGF signaling in olfactory sensory map formation and axon guidance. Neuron 57, 847-857. PMID: 18367086 PMCID: PMC2364597
Cancer Genome Atlas Research Network. 2008. Comprehensive genomic characterization defines human glioblastoma genes and core pathways. Nature 455, 1061-1068. PMID: 18772890 PMCID: PMC2671642
Cameron, P., M. Hiroi, J. Ngai, and K. Scott. 2010. The molecular basis for water taste in Drosophila. Nature 465, 91-96. PMID: 20364123 (Free PMC Article)
Fletcher, R.B., M.S. Prasol, J. Estrada, A. Baudhuin, K. Vranizan, Y.G. Choi, and J. Ngai. 2011. p63 regulates olfactory stem cell self-renewal and differentiation. Neuron 72, 748-759. PMID: 22153372 PMCID: PMC3240811
Ferreira, T., S.R. Wilson, Y.G. Choi, D. Risso, S. Dudoit, T.P. Speed and J. Ngai. 2014. Silencing of odorant receptor genes by G protein bg signaling ensures the expression of one odorant receptor per olfactory sensory neuron. Neuron 81, 847-859. PMID: 24559675
Fletcher*, R.B., D. Das*, L. Gadye, K.N. Street, A. Baudhuin, A. Wagner, M.B. Cole, Q. Flores, Y.G. Choi, N. Yosef, E. Purdom, S. Dudoit, D. Risso, and J. Ngai. 2017. Deconstructing olfactory stem cell trajectories at single cell resolution. Cell Stem Cell 20, 817-830. PMID: 28506465 PMCID: PMC5484588 * equal contribution
Gadye*, L., D. Das*, M.A. Sanchez*, K.N. Street, A. Baudhuin, A. Wagner, M.B. Cole, Y.G. Choi, N. Yosef, E. Purdom, S. Dudoit, D. Risso, J. Ngai and R.B Fletcher. 2017. Injury activates transient olfactory stem cell states with diverse lineage capacities. Cell Stem Cell 21, 775–790. PMID: 29174333 PMCID: PMC5728414 * equal contribution
Ecker, J.R., D.H. Geschwind, A.R. Kriegstein, J. Ngai*, P. Osten, D. Polioudakis, A. Regev, N. Sestan, I.R. Wickersham and H. Zeng. 2017. The BRAIN Initiative Cell Census Consortium: lessons learned toward generating a comprehensive brain cell atlas. Neuron 96, 542-557. PMID: 29096072 PMCID: PMC5689454 * Corresponding author
Last Updated 2019-02-27