Microbiology & Immunology
Tumor Immunology, Cancer Immunotherapy, Hematopoietic Cell Transplantation, Graft-versus-Host Disease, Graft-versus-Leukemia Effect View Xue-Zhong Yu bio
The research scope of Dr. Yu’s laboratory (Yu Lab) is in tumor immunology and cancer immunotherapy. The researchers in Yu’s Lab have been focusing on two lines of basic and translational studies:
Allogeneic Hematopoietic Cell Transplantation (allo-HCT). Acting through donor lymphocyte-mediated mechanisms termed the graft-versus-leukemia (GVL) effect, allo-HCT is an effective therapy for hematological malignancies such as leukemia. However, graft-versus-host disease (GVHD) remains a prominent cause of transplant-related morbidity and mortality after allo-HCT. Despite advances in patient care and pharmacologic prophylactic strategies, the incidence of GVHD, especially cGVHD, has not been substantially reduced over the years. Furthermore, corticosteroids remain as the first line therapy for GVHD and frequently fail with life-threatening consequences. Yu Lab focuses on defining the cellular and molecular mechanisms that regulate the pathogenicity of allogeneic T and B cells in GVHD, and on developing new and effective therapies to prevent and treat GVHD.
Adoptive T-cell Therapy (ACT). The adaptive immune system has the capacity to recognize and kill malignant cells. However, immune tolerant mechanisms that normally protect healthy tissues from autoimmune attack prevent the development of effective anti-tumor immunity. Tumors use numerous immunosuppressive mechanisms to evade otherwise effective T-cell responses. Despite promising results achieved by targeting one or more of the immune evasion mechanisms, there is clearly room for improvement because only a subset of cancer patients usually respond to current treatment. Aiming at understanding T-cell response against tumor and promoting anti-tumor activity, Yu Lab is interested in investigating T-cell activation, differentiation, persistence, migration, and metabolism in immunotherapy against cancer.
Heejin Choi, MD, PhD
Research Technologist I
Linlu Tian, MD, PhD
Yongxia Wu, MD, PhD
Research Assistant Professor
Kaipo Yang, MD
Visiting Scholar, Yu Lab
The Absence of IL-12Rβ2 Expression on Recipient Nonhematopoietic Cells Diminishes Acute Graft-versus-Host Disease in the Gastrointestinal Tract.
(Bastian D, Sui X, Choi HJ, Wu Y, Tian L, Yang K, Liu C, Liu Y, Yu XZ.) J Immunol. 2023 Feb 15;210(4):486-495 PMID: 36548465 PMCID: PMC9938950 SCOPUS ID: 2-s2.0-85147317750 12/23/2022
The splanchnic mesenchyme is the tissue of origin for pancreatic fibroblasts during homeostasis and tumorigenesis.
(Han L, Wu Y, Fang K, Sweeney S, Roesner UK, Parrish M, Patel K, Walter T, Piermattei J, Trimboli A, Lefler J, Timmers CD, Yu XZ, Jin VX, Zimmermann MT, Mathison AJ, Urrutia R, Ostrowski MC, Leone G.) Nat Commun. 2023 Jan 03;14(1):1 PMID: 36596776 PMCID: PMC9810714 SCOPUS ID: 2-s2.0-85145429848 01/04/2023
Leukemia inhibitory factor protects against graft-versus-host disease while preserving graft-versus-leukemia activity.
(Wang J, Chang CY, Yang X, Zhou F, Liu J, Zhu S, Yu XZ, Liu C, O'Sullivan TE, Xie P, Feng Z, Hu W.) Blood. 2022 Nov 10;140(19):2076-2090 PMID: 35981499 PMCID: PMC9837439 SCOPUS ID: 2-s2.0-85140086530 08/19/2022
The druggable transcription factor Fli-1 regulates T cell immunity and tolerance in graft-versus-host disease.
(Schutt SD, Wu Y, Kharel A, Bastian D, Choi HJ, Hanief Sofi M, Mealer C, McDaniel Mims B, Nguyen H, Liu C, Helke K, Cui W, Zhang X, Ben-David Y, Yu XZ.) J Clin Invest. 2022 Nov 01;132(21) PMID: 36074578 PMCID: PMC9621143 SCOPUS ID: 2-s2.0-85141004782 09/09/2022
S1P/S1PR1 signaling differentially regulates the allogeneic response of CD4 and CD8 T cells by modulating mitochondrial fission.
(Tian L, Wu Y, Choi HJ, Sui X, Li X, Sofi MH, Kassir MF, Chen X, Mehrotra S, Ogretmen B, Yu XZ.) Cell Mol Immunol. 2022 Nov;19(11):1235-1250 PMID: 36071219 PMCID: PMC9622814 SCOPUS ID: 2-s2.0-85137418710 09/08/2022
Ceramide synthase 6 impacts T-cell allogeneic response and graft-versus-host disease through regulating N-RAS/ERK pathway.
(Sofi MH, Tian L, Schutt S, Khan I, Choi HJ, Wu Y, Bastian D, Ticer T, Kassir MF, Atilgan FC, Kim J, Sui X, Zivkovic A, Mehrotra S, O'Bryan JP, Stark H, Martin PJ, Ogretmen B, Yu XZ.) Leukemia. 2022 Jul;36(7):1907-1915 PMID: 35513703 PMCID: PMC9256768 SCOPUS ID: 2-s2.0-85129354225 05/06/2022
MicroRNA-31 regulates T-cell metabolism via HIF1α and promotes chronic GVHD pathogenesis in mice.
(Wu Y, Mealer C, Schutt S, Wilson CL, Bastian D, Sofi MH, Zhang M, Luo Z, Choi HJ, Yang K, Tian L, Nguyen H, Helke K, Schnapp LM, Wang H, Yu XZ.) Blood Adv. 2022 May 24;6(10):3036-3052 PMID: 35073581 PMCID: PMC9131913 SCOPUS ID: 2-s2.0-85130628553 01/25/2022
Sphingolipid metabolism in T cell responses after allogeneic hematopoietic cell transplantation.
(Tian L, Ogretmen B, Chung BY, Yu XZ.) Front Immunol. 2022;13:904823 PMID: 36052066 PMCID: PMC9425084 SCOPUS ID: 2-s2.0-85137086832 09/03/2022
Nuclear PFKP promotes CXCR4-dependent infiltration by T cell acute lymphoblastic leukemia.
(Gao X, Qin S, Wu Y, Chu C, Jiang B, Johnson RH, Kuang D, Zhang J, Wang X, Mehta A, Tew KD, Leone GW, Yu XZ, Wang H.) J Clin Invest. 2021 Aug 16;131(16) PMID: 34255748 PMCID: PMC8363288 SCOPUS ID: 2-s2.0-85113146308 07/14/2021
Aging-dependent mitochondrial dysfunction mediated by ceramide signaling inhibits antitumor T cell response.
(Vaena S, Chakraborty P, Lee HG, Janneh AH, Kassir MF, Beeson G, Hedley Z, Yalcinkaya A, Sofi MH, Li H, Husby ML, Stahelin RV, Yu XZ, Mehrotra S, Ogretmen B.) Cell Rep. 2021 May 04;35(5):109076 PMID: 33951438 PMCID: PMC8127241 SCOPUS ID: 2-s2.0-85105099130 05/06/2021
Donor T-Cell Repertoire Profiling in Recipient Lymphoid and Parenchyma Organs Reveals GVHD Pathogenesis at Clonal Levels After Bone Marrow Transplantation in Mice.
(Wu Y, Fu J, Wang H, Yu XZ.) Front Immunol. 2021;12:778996 PMID: 34950143 PMCID: PMC8688739 SCOPUS ID: 2-s2.0-85121630632 12/25/2021
XBP-1s Promotes B Cell Pathogenicity in Chronic GVHD by Restraining the Activity of Regulated IRE-1α-Dependent Decay.
(Choi HJ, Tang CA, Tian L, Wu Y, Sofi MH, Ticer T, Schutt SD, Hu CA, Yu XZ.) Front Immunol. 2021;12:705484 PMID: 34659198 PMCID: PMC8517405 SCOPUS ID: 2-s2.0-85117251520 10/19/2021