Department of Neuroscience

Research Abstract

Microglia and other related immune cells are increasingly recognized to be essential players in central nervous system function and almost all neurological diseases. As we gain more knowledge about microglial biology—one of the fastest growing fields at the nexus of neuroscience, immunology and hematopoiesis, numerous fundamental questions remain to be answered, such as: How is microglia fate specified? How do microglia develop? How heterogeneous are microglia? How do microglia age? How do microglia contribute to brain development, aging and disease?

My lab is broadly interested in neuroimmunology with a focus on microglial biology. Particularly, we are interested in combining cutting-edge single-cell genomic technologies with in vitro and in vivo genetic, molecular and cellular tools to investigate microglial development, heterogeneity and mechanisms of neuro-immune interactions underlying brain structure and disease. We try to address two major questions: (1) how microglia (and other immune cells) are different in development, homeostasis and aging, and related to that, how these different populations of microglia interact with other neural cells to control brain development and functioning; (2) how microglial fate is specified and diverged from other tissue macrophages during early embryonic development. By studying these questions, the overarching goal is to gain a better understanding of microglial functions in the establishment of the nervous system, as well as how changes in these functions contribute to neurological diseases.

Selected Publications

• Kodama L, Guzman E, Etchegaray JI, Li Y, Sayed FA, Zhou L, Zhou Y, Zhan L, Le D, Udeochu JC, Clelland CD, Cheng Z, Yu G, Li Q, Kosik KS, Gan L. Microglial microRNAs mediate sex-specific response to tau pathology. Nat Neurosci. 2019 Dec 23. doi: 10.1038/s41593-019-0560-7
• Zhou L, Li Q. Isolation of region-specific microglia from one adult mouse brain hemisphere for deep single-cell RNA sequencing. J Vis Exp. 2019 Dec 3;(154). doi: 10.3791/60347.
• Marton RM, Miura Y, Sloan SA, Li Q, Revah O, Levy RJ, Huguenard JR, Pașca SP. Differentiation and maturation of oligodendrocytes in human three-dimensional neural cultures. Nat Neurosci. 2019 Mar;22(3):484-491. doi: 10.1038/s41593-018-0316-9.
• Li Q, Cheng Z, Zhou L, Darmanis S, Neff NF, Okamoto J, Gulati G, Bennett ML, Sun LO, Clarke LE, Marschallinger J, Yu G, Quake SR, Wyss-Coray T, Barres BA. Developmental Heterogeneity of Microglia and Brain Myeloid Cells Revealed by Deep Single-Cell RNA Sequencing. Neuron. 2019 Jan 16;101(2):207-223.e10. doi: 10.1016/j.neuron.2018.12.006. Selected as Best of Neuron 2018 and 2019.
• Sun LO, Mulinyawe SB, Collins HY, Ibrahim A, Li Q, Simon DJ, Tessier-Lavigne M, Barres BA. Spatiotemporal Control of CNS Myelination by Oligodendrocyte Programmed Cell Death through the TFEB-PUMA Axis. Cell. 2018 Dec 13;175(7):1811-1826.e21. doi: 10.1016/j.cell.2018.10.044.
• The tabula Muris consortium. Single-cell transcriptomics of 20 mouse organs creates a Tabula Muris. Nature. 2018 Oct;562(7727):367-372. doi: 10.1038/s41586-018-0590-4.
• Li Q, Barres BA. Microglia and macrophages in brain homeostasis and disease. Nat Rev Immunol. 2018 Apr;18(4):225-242. doi: 10.1038/nri.2017.125.
• Li Q, Barish S, Okuwa S, Maciejewski A, Brandt AT, Reinhold D, Jones CD, Volkan PC. A Functionally Conserved Gene Regulatory Network Module Governing Olfactory Neuron Diversity. PLoS Genet. 2016 Jan;12(1):e1005780. doi: 10.1371/journal.pgen.1005780.
• Li Q, Barish S, Okuwa S, Volkan PC. Examination of Endogenous Rotund Expression and Function in Developing Drosophila Olfactory System Using CRISPR-Cas9-Mediated Protein Tagging. G3 (Bethesda). 2015 Oct 23;5(12):2809-16. doi: 10.1534/g3.115.021857.
• Li Q, Ha TS, Okuwa S, Wang Y, Wang Q, Millard SS, Smith DP, Volkan PC. Combinatorial rules of precursor specification underlying olfactory neuron diversity. Curr Biol. 2013 Dec 16;23(24):2481-90. doi: 10.1016/j.cub.2013.10.053.

For a complete list of Dr. Li's publications, click here.