Possible Rotation Projects:
Identify key cell-cell communication networks in the tumor microenvironment using single cell spatial transcriptomics data
Generate ML algorithms to predict how gene perturbations can affect cellular neighborhoods in the tissue
Generate new algorithms to analyze spatial temporal single cell data.
Training Technologies Used:
Spatial Transcriptomics, CRISPR based gene editing, single cell RNA-seq, single cell TCR-seq, Single cell ATAC-seq, and single cell proteomics.
- B.S.,Biological Sciences, University of Chicago
- Ph.D.,Immunology, Harvard University
- Postdoc,Genomics Immunology, University of California San Francisco
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. PMC8059935. (#co-corresponding authors)
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. Cell. 2015 Dec 3;163(6):1400-12 PMC4671824. (*Equal contributions).
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. PMC3459594.
Lee Y*, Mitsdoerffer M*, Sobel RA, Kuchroo VK. IL-21R signaling is critical for induction of spontaneous experimental autoimmune encephalomyelitis. J Clin Invest. 2015 Nov 2;125(11):4011-20. PMC4639966.
Mitsdoerffer M, Lee Y, Jäger A, Kim HJ, Korn T, Kolls JK, Cantor H, Bettelli E, Kuchroo VK. Proinflammatory T helper type 17 cells are effective B-cell helpers. Proc Natl Acad Sci U S A. 2010 Aug 10;107(32):14292-7. PMC2922571.
Lee Y*, Auh SL, Wang Y, Burnette B, Wang Y, Meng Y, Beckett M, Sharma R, Chin R, Tu T, Weichselbaum RR, Fu YX. Therapeutic effects of ablative radiation on local tumor require CD8+ T cells: changing strategies for cancer treatment. Blood. 2009. Jul 16;114(3):589-95. PMC2713472.
Yu P, Lee Y, Liu W, Krausz T, Chong A, Schreiber H, Fu YX. Intratumor depletion of CD4+ cells unmasks tumor immunogenicity leading to the rejection of late-stage tumors. J Exp Med. 2005. 201(5):779-91. PMC2212829.
Yu P, Lee Y, Liu W, Chin RK, Wang J, Wang Y, Schietinger A, Philip M, Schreiber H, and Fu YX. 2004. Priming of naive T cells inside tumors leads to eradication of established tumors. Nat Immunol 2004. 5(2):141-149. PMID: 14704792.
Yu P, Lee Y, Wang Y, Christiansen P, Liu X, Auh S, Gajewski TF, Schreiber H, Wang X, Fu YX. Targeting the primary tumor to generate CTL for the effective eradication of spontaneous metastasis. Journal of Immunology. 2007. 179(3):1960-8. PMC2387226.
Lee Y, Chin RK, Christiansen P, Sun Y, Tumanov AV, Wang J, Chervonsky AV, Fu YX. Recruitment and activation of naive T cells in the islets by lymphotoxin beta receptor-dependent tertiary lymphoid structure. Immunity. 2006 Sep;25(3):499-509. PMID: 16934497.
The Lee laboratory delves into the immunological mechanisms governing cellular interactions within the tissue microenvironment. Our focus is to understand [YL1] how 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.
