Shanghai Jiao Tong University School of Medicine 

Name: Junke Zheng

Title： Professor

Email: zhengjunke@shsmu.edu.cn

Tel: 86-21-63846590 (ext:776915)

Research Interests

1. Immune inhibitory receptor mediated signaling in the activities of leukemia stem cells. Immune checkpoint blockade therapy has been successful in treating some types of cancer but has not shown clinical benefits for treating many types of acute myeloid leukemia (AML). We found that certain immune inhibitory receptors that are expressed by normal immune cells are also present on leukemia cells. We recently revealed unexpected roles of several immune inhibitory receptors (CD244, LILRB2 and LILRB4) in promoting AML development. For example, CD244 co-operates with c-Kit to activate SHP-2 signaling to dephosphorylate p27 and maintain its stability to promote leukemia development. LILRB4 supports tumor cell infiltration into tissues and suppresses T cell activity via a signaling pathway that involves APOE, LILRB4, SHP-2, uPAR and ARG1 in AML cells. Deletion of LILRB4 or the use of antibodies to block LILRB4 signaling impeded AML development. Immune inhibitory receptors may   represent   a   compelling   target   for  thetreatment of AML.

2.Metabolic regulations of the stemness of hematopoietic stem cells and leukemia stem cells. We have made several important findings related to glucose/amino acid metabolisms in hematopoiesis and leukemogenesis. For example, by using a sensitive NADH/NAD+ sensor, we demonstrate that there exist totally different metabolic profiles between acute myeloid leukemia and lymphoid leukemia cells. Our results also show that fetal liver hematopoietic stem cells prefer to utilizing oxidative phosphorylation as the main energy source.

Ten Selected Papers

*co-corresponding authors; #co-first authors

1.Chen C#, Hao X#, Lai X#, Liu L#, Zhu J#, Shao H, Huang D, Gu H, Zhang T, Yu Z, Xie L, Zhang X, Yang Y, Xu J, Zhao Y, Lu Z, Zheng J. Oxidative phosphorylation enhances the leukemogenic capacity and resistance to chemotherapy of B cell acute lymphoblastic leukemia. Sci Adv., 7(11):eabd6280, 2021.

2.He X#, Wan J#, Yang X, Zhang X, Huang D, Li X, Zou Y, Chen C, Yu Z, Xie L, Zhang Y, Liu L, Li S, Zhao Y, Shao H, Yu Y, Zheng J. Bone marrow niche ATP levels determine leukemia-initiating cell activity via P2X7 in leukemic models. J Clin Invest., 131(4):e140242, 2021.

3.Gu H#, Chen C#, Hao X#, Su N#, Huang D, Zou Y, Lin S, Chen X, Zheng D, Liu L, Yu Z, Xie L, Zhang Y, He X, Lai Xi, Zhang X, Chen GQ, Zhao Y, Yang Y, Loscalzo J, Zheng J*, MDH1- mediated malate-aspartate NADH shuttle maintains the activities of fetal liver hematopoietic stem cells, Blood, 136(5):553-571, 2020.

4.Hao X#, Gu H#, Chen C#, Huang D, Zhao Y, Xie L, ZouY, Shu H, Zhang Y, He X, Lai X, Zhang X, Zhou B, Zhang CC, Chen GQ, Yu Z, Yang Y, Zheng J. Metabolic imaging reveals a unique preference of symmetric cell division and homing of leukemia-initiating cells in an endosteal niche. Cell Metab., 29(4):950-965, 2019 (cover story).

5.Deng M#, Gui X#, Kim J#, Xie L, Chen W, Li Z, He L, Chen Y, Chen H, Luo W, Lu Z, Xie J, Churchill H, Xu Y, Zhou Z, Wu G, Yu C, John S, Hirayasu K, Nguyen N, Liu X, Huang F, LLi L, HDeng H, Tang H, Sadek A, Zhang L, Huang T, Zou Y, Chen B, Zhu H, Arase H, Xia N, Jiang Y, Collins R, You M, Homsi J, Unni N, Lewis C, Chen GQ, YX, X. Liao X, An Z, Zheng J*, Zhang N, and Zhang CC. LILRB4 signaling in leukemia cells mediates T cell suppression and tumor infiltration. Nature, 562(7728):605-609, 2018.

6.Liu X#, Zhang F#, Zhang Y#, Li X#, Chen C#, Zhou M, Yu Z, Zhao Y, Hao X, Tang B, Zhu L, Liu G, Xie L, Gu H, Shao H, Xia F, Yin C, Tao M, Xie J, Zhang CC, Yang Y, Sun H, Chen GQ, Zheng J. PPM1K regulates hematopoiesis and

leukemogenesis through CDC20-mediated

ubiquitination of MEIS1 and p21. Cell Rep, 23(5):1461-1475, 2018.

7.Zhang Y#, Xia F#, Liu X#, Yu Z#, Xie L, Liu L, Chen C, Jiang H, Hao X, He X, Zhang F, Gu H, Zhu J, Bai H, Zhang CC, Chen GQ, Zheng J. JAM3 maintains leukemia-initiating cell self- renewal through LRP5/AKT/β-catenin/CCND1 signaling. J Clin Invest., 128(5):1737-1751, 2018.

8.Xia F#, Zhang Y#, Xie L#, Jiang H#, Zeng H, Chen C, Liu L, He X, Hao X, Fang X, Liu X, Zhang F, Gu H, Wan J, Chen Y, Zhang CC, Chen GQ, Lu Y, Yu Z, Zheng J. B7-H4 enhances the differentiation of murine leukemia-initiating cells via the PTEN/AKT/RCOR2/RUNX1 pathways. Leukemia, 31:2260–2264, 2017.

9.Zhang F#, Liu X#, Chen C, Zhu J, Yu Z, Xie J, Xie L, Bai H, Zhang Ya, Fang X, Gu H, Wang C, Weng W, Zhang CC, Chen GQ, Liang A, Zheng J. CD244 maintains the proliferation ability of leukemia initiating cells through SHP-2/p27kip1 signaling. Haematologica, 102(4):707-718, 2017.

10、Gu H, Chen C, Hao X, Wang C, Zhang X, Li Z, Shao H, Zeng H, Yu Z, Xie L, Xia F, Zhang F, Liu X, Zhang Y, Jiang H, Zhu J, Wan J, Wang C, Weng W, Xie J, Tao M, Zhang CC, Liu J, Chen GQ, Zheng J. Sorting protein VPS33B regulates exosomal autocrine signaling to mediate hematopoiesis and leukemogenesis. J Clin Invest., 126(12): 4537-4553, 2016.