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Youjin Lee Ph.D.

  • Assistant Professor, Department of Immunology
  • Core Member, Center for Systems Immunology
  • Core Member, Tumor Microenvironment Center
  • PMI Graduate Faculty

    Education & Training

  • Postdoctoral Fellowship, University of California, San Francisco
  • Ph.D. – Harvard University
  • B.S. – University of Chicago
Representative Publications

Bioengineered spatially linked scRNA sequencing platform: Developed a novel single cell RNA-seq platform that simultaneously links spatial metadata.

Lee Y*#, Bogdanoff D*, Wang Y*, Hartoularos GC, Woo JM, Mowery CT, Nisonoff HM, Lee DS, Sun Y, Lee J, Mehdizadeh S, Cantlon J, Shifrut E, Ngyuen DN, Roth TL, Song YS, Marson A#, Chow ED#, Ye CJ#. XYZeq: Spatially resolved single-cell RNA sequencing reveals expression heterogeneity in the tumor microenvironment. Sci Adv. 2021 Apr 21;7(17):eabg4755. (#co-corresponding authors)

2. Determined the key gene signature that defines pathogenic vs non-pathogenic Th17 cells: Characterized pathogenic and non-pathogenic Th17 subsets in a mouse model of Multiple Sclerosis. Discovered and functionally validated cellular states of pathogenic Th17 cells that exist during autoimmune inflammation using single cell RNA sequencing.

a)  Gaublomme JT*, Yosef N*, Lee Y*, Gertner RS, Yang LV, Wu C, Satija R, Shalek AK, Kuchroo VK, Park H, Regev A. Single-cell genomics unveils critical regulators of Th17 cell pathogenicity. Cell. 2015 Dec 3;163(6):1400-12. (*Equal contributions).

b)  Lee Y, Awasthi A, Yosef N, Quintana FJ, Xiao S, Peters A, Wu C, Kleinewietfeld M, Kunder S, Hafler DA, Sobel RA, Regev A, Kuchroo VK. Induction and molecular signature of pathogenic Th17 cells. Nat Immunol. 2012. Oct;13(10):991-9

3. Defined the role of autoreactive T and B cells in spontaneous experimental autoimmune encephalomyelitis: Defined the critical role of IL-21R expression on both T and B cells to facilitate T-B cell crosstalk in the development of spontaneous autoimmune inflammation. Discovered that B cells were essential to drive T cell specific inflammation of a subset of EAE called neuromyelitis optica (NMO). In addition, Th17 cells can also drive B cell differentiation and function.

Lee Y*, Mitsdoerffer M*, Sobel RA, Kuchroo VK. IL-21R signaling plays a critical role in the T and B cell collaboration for the induction of spontaneous experimental autoimmune encephalomyelitis. J Clin Invest. 2015 Sep 28. pii: 75933.

Research Interests

What We Do

The Lee laboratory delves into the immunological mechanisms governing cellular interactions within the tissue microenvironment. Our focus is to understandhow these intricate dynamics dictate disease progression or resolution, particularly in autoimmune diseases and cancer. Our overarching objective is to establish a causal understanding between immune responses and the spatial organization of the cellular networks within the tissue landscape.

Our approach involves the application of a novel single-cell spatial sequencing platform, XYZeq. This technology enables us to achieve high resolution single-cell RNA sequencing, facilitating a comprehensive exploration of individual cellular transcriptomes while preserving the spatial context. By integrating spatial information with transcriptomic data, we aim to unravel the cellular heterogeneity that dictates distinct cell states, circuits, and behavior within the tissue microenvironment.

In tandem with these efforts, we leverage forward genetics using the CRISPR/Cas9 system to discover novel genes driving critical cellular phenotypes. Our research incorporates the use of human primary T cells and animal models of human diseases, thus providing a multifaceted approach to understanding disease mechanisms. We are working to couple CRISPR screens with spatially resolved single-cell RNA-seq platforms to not only map the cellular neighborhoods within the tissue microenvironment, but also to permit deeper insights into the cell-to-cell communication networks that shape the immune response.

 Disease Areas

  • Autoimmune Diseases
  • Cancer biology and Immunotherapy
  • Neurodegenerative Diseases

Research Interests

  • Spatial Transcriptomics
  • Systems Biology
  • Functional Genomics
  • CRISPR Genome Engineering
  • T cell immunology