Personal Introduction

Junke Zheng, Ph.D., Principle Investigator, and the winner of National Science Fund for Distinguished Young Scholars. Dr. Zheng got his Ph.D for Developmental Biology at Shanghai Jiao Tong University School of Medicine in 2007. He had the Postdoc (Instructor) training at Alec Zhang’s Lab (2007-2012), Department of Physiology, University of Texas Southwestern Medical Center at Dallas, USA. He was nominated as the Professor in Shanghai Jiao Tong University School of Medicine in 2012. Dr, Zheng’s Lab mainly focuses on the studies of the metabolic regulation of hematopoietic stem cells (HSCs) and leukemia stem cells (LSCs) and the identification of the potential immunotherapeutic targets for leukemia treatment. Dr. Zheng has made several important findings in the fate determinations of HSCs/LSCs related to intrinsic metabolic pathways or extrinsic niche components. He demonstrated that glucose and amino acid metabolisms play critical roles in the maintenance of HSC or LSC activities, and that bone marrow niche factors (such as ANGTPLs and APOE) sustains HSC or LSC stemness through the immune inhibitory receptor LILRBs. These findings have been published in Nature, Cell Metabolism (cover story), Blood (cover story), JCI and other high-profile journals. Dr. Zheng has also applied for several domestic and overseas patents according to these original findings. By using their established unique techniques, including metabolic sensors, bone marrow niche imaging and immunotherapeutic platforms (antibody and CAR-T), they currently aim to: 1) unravel the intrinsic metabolic properties of HSCs/LSCs and their potential connections with bone marrow niches; 2) identify novel targets and potential strategies for the leukemia immunotherapy. These studies will open a new avenue for understanding the underlying mechanisms by which HSCs and LSCs maintain their stemness, and provide some ideal metabolic or immune candidate targets for the treatments of different types of leukemias or solid cancers.

Publications

1. Chen C, Lai X, Zhang Y, Xie L, Yu Z, Dan S, Jiang Y, Chen W, Liu L, Yang Y, Huang D, Zhao Y, Zheng J. NADPH metabolism determines the leukemogenic capacity and drug resistance of AML cells. Cell Rep., 5;39(1):110607; 2022

2. Yu Z, Yang W, He X, Chen C, Li W, Zhao L, Liu L, Liu LJ, Xie L, Zhang Y, Zheng J. Endothelial cell-derived angiopoietin-like protein 2 supports hematopoietic stem cell activities in bone marrow niches. Blood, 139(10);1529-1540; 2022 (Cover story)

3. He X, Zhang Y, Xu Y, Xie L, Yu Z, Zheng J. Function of the P2X7 receptor in hematopoiesis and leukemogenesis. Exp Hematol., 104:40-47, 2021

4. 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

5. 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, 2021a

6. Huang D#, Sun G#, Hao X#, He X#, Zheng Z, Chen C, Yu Z, Xie L, Ma S, Liu L, Zhou BO, Cheng H*, Zheng J*, Cheng T*.ANGPTL2-containing small extracellular vesicles from vascular endothelial cells accelerate leukemia progression. J Clin Invest. 131(1):e138986, 2021b (co-correspondence)

7. 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

8. 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 (封面文章)

9. Huang D, Chen C, Hao X, Gu H, Xie L, Yu Z, Zheng J. Metabolic Regulations in Hematopoietic Stem Cells. Adv Exp Med Biol.1143:59-74,2019

10. 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 (co-correspondence)

11. Peng Y, Yu H, Hao X, Dong W, Yin X, Lin M, Zheng J*, Zhou B*. Luteinizing hormone signaling restricts hematopoietic stem cell expansion during puberty. EMBO J., e98984, 2018 (co-correspondence)

12. 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

13. 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

14. 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

15. 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

16. Fang X, Chen C, Xia F, Yu Z, Zhang Y, Zhang F, Gu H, Wan J, Zhang X, Weng W, Zhang CC, Chen G, Liang A, Xie L, Zheng J. CD274 promotes cell cycle entry of leukemia-initiating cells through JNK/Cyclin D2 signaling. J Hemato & Oncol., 9:124, 2016

17. 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

18. Zhang F, Zheng J*, Kang X, Deng M, Lu Z, Kim J, Zhang CC. Inhibitory leukocyte immunoglobulin-like receptors in cancer development. Sci China Life Sci, 58(12): 1216-1225, 2015(co-correspondence)

19. Kocabas F, Xie L, Xie J, Yu Z, DeBerardinis R J, Kimura W, Thet S, Elshamy A F, Muralidhar S, Liu X, Chen C, Sadek H A , Zhang CC and Zheng J. Hypoxic Metabolism in Human Hematopoietic Stem Cells. Cell Biosci, 5:39, 2015

20. Fan X, Shi P, Dai J, Lu Y, Chen X, Liu X, Zhang K, Wu X, Sun Y, Wang K, Zhu L, Zhang CC, Zhang J, Chen GQ, Zheng J*, Liu J. Paired immunoglobin-like receptor B regulates platelet activation. Blood, 124(15):2421-2430 , 2014 (co-correspondence)

21. Deng M, Lu Z, Zheng J*, Wan X, Chen X, Hirayasu K, Sun H, Lam Y, Chen L, Wang Q, Song C, Huang N, Gao GF, Jiang Y, Arase H, Zhang CC. A motif in LILRB2 critical for Angptl2 binding and activation. Blood, 124(6):924-35, 2014(co-correspondence)

22. Zheng J, Lu Z, Kocabas F, Böttcher RT, Costell M, Kang X, Liu X, Deberardinis RJ, Wang Q, Chen G, Sadek H, Zhang CC. Profilin 1 is essential for retention and metabolism of mouse hematopoietic stem cells in bone marrow. Blood, 13;123(7):992-1001,2014

23. Zheng J, Umikawa M, Cui C, Li J, Chen X, Zhang C, Huynh H, Kang X, Silvany R, Wan X, Ye J, Cantó AP, Chen SH, Wang HY, Ward ES, Zhang CC. Immune inhibitory receptors bind to angiopoietin-like proteins and support the stemness of hematopoietic and leukemia stem cells. Nature, 485(7400):656-660, 2012

24. Kocabas F#, Zheng J#, Thet S, Copeland NG, Jenkins NA, DeBerardinis RJ, Zhang C, Sadek HA. Meis1 regulates the metabolic phenotype and oxidant defense of hematopoietic stem cells. Blood, 13(25):4963-4972, 2012 (co-first author)

25. Zheng J, Umikawa M, Zhang S, Huynh H, Silvany R, Chen BP, Chen L, Zhang CC. Ex vivo expanded hematopoietic stem cells overcome the MHC barrier in allogeneic transplantation. Cell Stem Cell, 9(2):119-130, 2011

26. Zheng J, Huynh H, Umikawa M, Silvany R, Zhang CC. Angiopoietin-like protein 3 supports the activity of hematopoietic stem cells in the bone marrow niche. Blood, 117(2):470-479, 2011

27. Zheng J, Song C, Zhang CC. A new chapter: hematopoietic stem cells are direct players in immunity. Cell Biosci., 1: 33, 2011

28. Simsek T#, Kocabas F#, Zheng J#, Deberardinis RJ, Mahmoud AI, Olson EN, Schneider JW, Zhang CC, Sadek HA. The distinct metabolic profile of hematopoietic stem cells reflects their location in a hypoxic niche. Cell Stem Cell, 7(3):380-390, 2010 (co-first author)

29. Zheng J, Xia X, Ding H, Yan A, Hu S, Gong X, Zong S, Zhang Y, Sheng HZ. Erasure of the paternal transcription program during spermiogenesis: the first step in the reprogramming of sperm chromatin for zygotic development. Dev Dyn., 237(5): 1463-1476, 2008

30. Yang Y#, Zheng J#, Zhou X, Yang Z, Tan Y, Liu A, Gao X, Chang Z, Sheng HZ. Potential treatment of liver related disorders with in vitro expanded human liver precursors. Differentiation, 75(10): 928-938, 2007 (co-first author)

31. Gao T#, Zheng J#, Xing F#, Fang H, Sun F, Yan A, Gong X, Ding H, Tang F, Sheng HZ. Nuclear reprogramming: the strategy used in normal development is also used in somatic cell nuclear transfer and parthenogenesis. Cell Res., 17(2): 135-150, 2007(co-first author)

32. Chen B#, Shi J#, Zheng J#, Chen Y, Wang K, Yang Q, Chen X, Yang Z, Zhou X, Zhu Y, Chu J, Liu A, Sheng HZ. Differentiation of liver cells from human primordial germ cell-derived progenitors. Differentiation, 75(5): 350-359, 2007 (co-first author)

Book Chapters

1. Huynh H, Kaba M, Rudra S, Zheng J, Wu CJ, Lodish HF, Zhang CC. IGFBP2 Supports ex vivo Expansion of Hematopoietic Stem Cells, Book Title: IGFs: Local Repair and Survival Factors Throughout Life Span. Springer-Verlag Berlin Heidelberg, 2010

2. Kocabas F, Zheng J, Zhang CC and Sadek HA. Metabolic Characterization of Hematopoietic Stem Cells. Hematopoietic Stem Cell Protocols. Springer. 2014

3. Huang D, Chen C, Zheng J. Leukemia Stem Cells in Hematologic Malignancies: metabolic regulations in hematopoietic stem cells, Springer, 2019, ISBN 978-1-4939-1132-5.

4. Zhang Y, Zheng J. Regulation of Cancer Immune Checkpoints: Functions of Immune Checkpoint, Springer, 2020, ISBN 978-981-15-3265-8.

Patent

1. Chen SH, Zhang CC, Zheng J, Masato U, Kang X. 2012. Compositions and methods for modulating pro-inflammatory immune response. U.S. patent application 61/653,337

2. Zhang CC, Liu Y, Zheng J, Deng M, Chen C, Liu W. 2014. Novel compound supports hematopoietic stem cells and red blood cells. U.S. patent application 62/003,969

3. Zhang CC, Liu Y, Zheng J, Deng M, Chen C, Liu W. 2015. Novel compound supports hematopoietic stem cells and red blood cells. Canada, patent application 2,950,269

4. Zhang CC, Liu Y, Zheng J, Deng M, Chen C, Liu W. 2014. Novel compound supports hematopoietic stem cells and red blood cells.15798855.1-1453 PCT/US201503352

5. Bernstein ID, Zhang CC, Zheng J, Deng M, Lu Z. 2014. LILRB2 and Notch-mediated expansion of hematopoietic precursor cells. U.S. patent application 62/005,746

6. Zhang CC, Deng M, An Z, Xiong W, Zhang N, Zheng J, Anti-LILRB antibodies and their use in detecting and treating cancer. 2015 U.S. patent application 62/129,572

7. Yuzheng Zhao, Junke Zheng, Yi Yang, Chiqi Chen, Xie Li, Ting Li, Zhuo Zhang. Cancer therapeutic targets and applicaions. patent application# 202110262093.5，