Molecular Pharmacology Program
The Xinbo Yang Lab
The Xinbo Yang lab is interested in studying the T cell receptor (TCR) specificity in Cancer and autoimmune disease. The patrolling T cells constantly scan host tissues to eliminate infected or malignant cells. Failure to recognize such cells leads to pathogen evasion or cancer. Whereas mis-recognizing healthy tissue can cause collateral tissue damage that led to autoimmune disease. We seek to understand the molecular basis of this fine-tuned self-foreign discrimination system by applying interdisciplinary approaches such as, antigen-discovery platforms, protein engineering techniques and structural biology tools. The isolated antigens and their parent proteins for ‘orphan’ TCRs would then allow specific perturbation on each target to see how T cell responses are affected. Such mechanistic studies will facilitate animal model generation to further understand disease pathogenesis and ultimately benefit pMHC based therapeutic development.
Yang X*, Nishimiya D*, Lochte S, Jude KM, Borowska M, Savvides CS, Dougan M, Su L, Zhao X, Piehler J, Garcia KC. (2023) Facile repurposing of peptide-MHC restricted antibodies for cancer immunotherapy. Nat. Biotechnol. 41, 932-943. PMID: 36593402. *Equal contribution
Yang X*, Garner LI*, Zvyagin IV*, Paley MA*, Komech EA, Jude KM, Zhao X, Fernandes RA, Hassman LM, Paley GL, Savvides CS, Brackenridge S, Quastel MN, Chudakov DM, Bowness P, Yokoyama WM, McMichael AJ, Gillespie GM, Garcia KC. (2022) Autoimmunity-associated T cell receptors recognize HLA-B*27-bound peptides. Nature. 612, 771-777. PMID: *Equal contribution
Hoover AR, Kaabinejadian S, Krawic J, Sun X, Naqash AR, Yin Q, Yang X, Garcia KC, Davis MM, Hildebrand WH, Chen WR. (2022) Localized ablative immunotherapy drives de novo CD8+ T-cell responses to poorly immunogenic tumors. J. Immunother. Cancer. 10, e004973. PMID: 36253002.
Zhao X, Kolawole EM, Chan W, Feng Y, Yang X, Gee MH, Jude KM, Sibener LV, Fordyce PM, Germain RN, Evavold BD, Garcia KC. Tuning T cell receptor sensitivity through catch bond engineering. Science. 376, eabl5282. PMID: 35389803.
Ali M, Giannakopoulou E, Li Y, Lehander M, Culleton SV, Yang W, Knetter C, Odabsai MC, Bollineni RC, Yang X, Foldvari Z, Boschen ML, Taraldsrud E, Stronen E, Toebes M, Hillen A, Mazzi S, H de Ru A, Janssen G, Kolstad N, Tjonnfjord GE, Lie BA, Griffioen M, Lehmannn S, Osnes LT, Buechner J, Garcia KC, Schumacher TN, van Veelen PA, Leisegan M, Jacobsen SEW, Woll P, Olweus J. (2021) T cells targeted to TdT kill leukemic lymphoblasts while sparing normal lymphocytes. Nat. Biotechnol. 40, 488-498. PMID: 34873326.
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