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.

Scientific Research Projects:

1. Key Program of National Natural Science Foundation of China (82430007); 2.3 million yuan; January, 2025 - December, 2029.

2. Key Research and Development Program of the Ministry of Science and Technology (special project for Development and Metabolism) (2024YFA1803500); 23 million yuan; November 2024 - November 2029; Chief Scientist.

3. Key Program of National Natural Science Foundation of China (32030030); 2.95 million yuan; January, 2021 - December, 2025.

4. Candidate for Outstanding Youth program of National Natural Science Foundation of China (81825001); 3.5 million yuan; January 2019 - December 2023.

5. Key Research and Development Program of the Ministry of Science and Technology (special project for Development and Metabolism) (2019YFA0801800); 4.56 million yuan; December 2019 - December 2024; Group Leader.

6. Key Research and Development Program of the Ministry of Science and Technology (special project for Stem Cell and Translational Research) (2018YFA0107000); 1.76 million yuan; January 2018 - December 2022; Group Member.

7. Innovative Research Group Project of National Natural Science Foundation of China (81721004); 1 million yuan; January 2018 - December 2023; Group Member.

8. Shanghai Outstanding Young Academic Leader project of Shanghai Science and Technology Commission (81422001); 0.4 million yuan; April 2019 - March 2022.

Publications

1. Chen X, Meng X, Zhang W, Zhang X, Zhang Y, Yang P, Liu Y, Bao F, Li S, Wang J, Yan C, Li C, Zhang L, Hao X, Liu J, Sun J, Wang Z, Tian Y, Zhu L, Hou Y, Liu Z, Li W, Mi L, Qi X, Yue Y, Du P, Chen G, Zheng J*, Dou L*, Jing H*, He A*. Cell-free chromatin state tracing reveals disease origin and therapy responses. Nature. 2026 Mar 4.

2. Li W, Zhang D, Peng E, Shen S, Alinejad-Rokny H, Liu Y, Zheng J*, Jiang C*, Ye Y*. HiST: Histological Images Reconstruct Tumor Spatial Transcriptomics via MultiScale Fusion Deep Learning. Adv Sci (Weinh). 2026 Mar;13(13):e14351.

3. Gu H, Weng L, Chen C, Hao X, Tao R, Qi X, Lai X, Liu L, Zhang T, Jiang Y, Wang J, Li WG, Yu Z, Xie L, Zhang Y, He X, Yu Y, Yang Y, Wu D, Zhao Y, Xu TL, Chen GQ, Zheng J*. Nonionotropic action of an acid-sensing ion channel inhibits leukemogenesis in the acidic bone marrow niche. J Clin Invest. 2025 Dec 15;135(24):e189051.

4. Wang F, Bao R, Xu S, Li W, Huang H, Li R, Ding X, Zhang Y, Yu X, Han Q, Du X, Wan J, Li S, Xiao Y, Zhao R, Cui X, Ye Y, Sun J, Zheng J*, Chen GQ*, Zou Q*. An age-related decrease in leptin contributes to CD8+ T cell aging in the tumor microenvironment. Cell Rep Med. 2025 Sep 16;6(9):102310.

5. Li, W., Sun, J., Sun, R., Wei, Y., Zheng, J.*, Zhu, Y.*, and Guo, T*. (2025). Integral-Omics: Serial Extraction and Profiling of Metabolome, Lipidome, Genome, Transcriptome, Whole Proteome and Phosphoproteome Using Biopsy Tissue. Anal Chem. 97, 1190-1198.

6. Chen C, Zhou X, Cao L, Yang W, Weng L, Yuan J, Zhou W, Yu Z, Zheng J*. The progression of multiple myeloma is regulated by LILRB1 via the GATA2-SAGE1 pathway. Br J Haematol. 2025 Jul;207(1):69-79.

7. Cao L, Zhao H, Zhou X, Yuan J, Weng L, Yu Z, Zheng J*, Chen C*. LILRB1 enhances the progression of diffuse large B-cell lymphoma through the CREB-SORBS3 pathway. Cell Oncol (Dordr). 2025 Aug;48(4):1005-1018.

8. Jiang, Y., Zhang, D., He, X., Chen, C., Xie, L., Liu, L., Yu, Z., Zhang, Y., Zheng, J.*, and Huang, D*. (2025). BCAT1 contributes to the development of TKI-resistant CML. Cell Oncol. 48, 411-424.

9. Zhang, Z., Chen, C., Li, X., Zheng, J*., and Zhao, Y*. (2024). Regulation of leukemogenesis via redox metabolism. Trends Cell Biol. 34, 928-941.

10. Xie, L., Chen, C., Zhang, T., Yang, W., Zheng, D., Cao, L., Yuan, J., Xu, Y., Zhang, Y., Liu, L., Liang, A., Yu, Z., and Zheng, J. (2024). LILRB4 regulates multiple myeloma development through STAT3-PFKFB1 pathway. Cell Death Dis. 15, 515.

11. Wang, G., Zhang, W., Ren, J., Zeng, Y., Dang, X., Tian, X., Yu, W., Li, Z., Ma, Y., Yang, P., Lu, J., Zheng, J.*, Lu, B.*, Xu, J.*, and Liang, A*. (2024). The DNA damage-independent ATM signalling maintains CBP/DOT1L axis in MLL rearranged acute myeloid leukaemia. Oncogene. 43, 1900-1916.

12. Huang, D., Yuan, Y., Cao, L., Zhang, D., Jiang, Y., Zhang, Y., Chen, C., Yu, Z., Xie, L., Wei, Y., Wan, J., and Zheng, J. (2024). Endothelial-derived small extracellular vesicles support B-cell acute lymphoblastic leukemia development. Cell Oncol. 47, 129-140.

13. Huang, D., Zhang, C., Xiao, M., Li, X., Chen, W., Jiang, Y., Yuan, Y., Zhang, Y., Zou, Y., Deng, L., Wang, Y., Sun, Y., Dong, W., Zhang, Z., Xie, L., Yu, Z., Chen, C., Liu, L., Wang, J., Yang, Y., Yang, J., Zhao, Y., and Zheng, J. (2023). Redox metabolism maintains the leukemogenic capacity and drug resistance of AML cells. Proc Natl Acad Sci U S A. 120, e2210796120.

14. He, X., Xu, Y., Huang, D., Yu, Z., Yu, J., Xie, L., Liu, L., Yu, Y., Chen, C., Wan, J., Zhang, Y., and Zheng, J. (2023). P2X1 enhances leukemogenesis through PBX3-BCAT1 pathways. Leukemia. 37, 265-275.

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

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

17. Sun, G., Gu, Q,, Zheng, J.*, cheng, H.*, and cheng, T*. (2022) Emerging roles of extracellular vesicles in normal and malignant hematopoiesis. J Clin Invest. 132, e160840

18. Huang, D., Sun, G., Hao, X., He, X., Zheng, Z., Chen, C., Yu, Z., Xie, L., Ma, S., Liu, L., Zhou, B.O., Cheng, H., Zheng, J.*, and Cheng, T*. (2021a). ANGPTL2-containing small extracellular vesicles from vascular endothelial cells accelerate leukemia progression. J Clin Invest. 131. 131, e138986

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

20. 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., and Zheng, J. (2021b). Bone marrow niche ATP levels determine leukemia-initiating cell activity via P2X7 in leukemic models. J Clin Invest. 131, e140242.

21. 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., and Zheng, J. (2021). Oxidative phosphorylation enhances the leukemogenic capacity and resistance to chemotherapy of B cell acute lymphoblastic leukemia. Sci Adv. 7, eabd6280

22. Gu, H., Chen, C., Hao, X., Su, N., Huang, D., Zou, Y., Lin, S.H., Chen, X., Zheng, D., Liu, L., Yu, Z., Xie, L., Zhang, Y., He, X., Lai, X., Zhang, X., Chen, G.Q., Zhao, Y., Yang, Y., Loscalzo, J., and Zheng, J. (2020). MDH1-mediated malate-aspartate NADH shuttle maintains the activity levels of fetal liver hematopoietic stem cells. Blood. 136, 553-571.

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

24. Hao, X., Gu, H., Chen, C., Huang, D., Zhao, Y., Xie, L., Zou, Y., Shu, H.S., Zhang, Y., He, X., Lai, X., Zhang, X., Zhou, B.O., Zhang, C.C., Chen, G.Q., Yu, Z., Yang, Y., and Zheng, J. (2019). Metabolic Imaging Reveals a Unique Preference of Symmetric Cell Division and Homing of Leukemia-Initiating Cells in an Endosteal Niche. Cell metabolism. 29, 950-965.e956. (cover story)

25. Huang, D., Chen, C., Xie, L., Yu, Z., Zheng, J. (2019). Hematopoietic stem cell metabolism and stemness. Blood Sci. 17;1(1):12-18.

26. Peng, Y.J., Yu, H., Hao, X., Dong, W., Yin, X., Lin, M., Zheng, J*., and Zhou, B.O. (2018). Luteinizing hormone signaling restricts hematopoietic stem cell expansion during puberty. Embo J. 37, e98984

27. Liu, X., Zhang, F., Zhang, Y., Li, X., Chen, C., Zhou, M., Yu, Z., Liu, Y., Zhao, Y., Hao, X., Tang, Y., Zhu, L., Liu, L., Xie, L., Gu, H., Shao, H., Xia, F., Yin, C., Tao, M., Xie, J., Zhang, C.C., Yang, Y., Sun, H., Chen, G.Q., and Zheng, J. (2018). PPM1K Regulates Hematopoiesis and Leukemogenesis through CDC20-Mediated Ubiquitination of MEIS1 and p21. Cell Rep. 23, 1461-1475.

28. 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., Li, L., Deng, H., Tang, H., Sadek, A.H., Zhang, L., Huang, T., Zou, Y., Chen, B., Zhu, H., Arase, H., Xia, N., Jiang, Y., Collins, R., You, M.J., Homsi, J., Unni, N., Lewis, C., Chen, G.Q., Fu, Y.X., Liao, X.C., An, Z., Zheng, J.*, Zhang, N.*, and Zhang, C.C*. (2018). LILRB4 signalling in leukaemia cells mediates T cell suppression and tumour infiltration. Nature. 562, 605-609.

29. 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, C.C., Chen, G.Q., and Zheng, J. (2018). JAM3 maintains leukemia-initiating cell self-renewal through LRP5/AKT/β-catenin/CCND1 signaling. J Clin Invest. 128, 1737-1751.

30. Zhang, F., Liu, X., Chen, C., Zhu, J., Yu, Z., Xie, J., Xie, L., Bai, H., Zhang, Y., Fang, X., Gu, H., Wang, C., Weng, W., Zhang, C.C., Chen, G.Q., Liang, A., and Zheng, J. (2017). CD244 maintains the proliferation ability of leukemia initiating cells through SHP-2/p27(kip1) signaling. Haematologica. 102, 707-718.

31. 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., Cheng, Y., Zhang, C.C., Chen, G.Q., Lu, Y., Yu, Z., and Zheng, J. (2017). B7-H4 enhances the differentiation of murine leukemia-initiating cells via the PTEN/AKT/RCOR2/RUNX1 pathways. Leukemia. 31, 2260-2264.

32. 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, C.C., Liu, J., Chen, G.Q., and Zheng, J. (2016). Sorting protein VPS33B regulates exosomal autocrine signaling to mediate hematopoiesis and leukemogenesis. J Clin Invest. 126, 4537-4553.

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

34. Zhang, F., Zheng, J.*, Kang, X., Deng, M., Lu, Z., Kim, J., and Zhang, C. (2015). Inhibitory leukocyte immunoglobulin-like receptors in cancer development. Sci China Life Sci. 58, 1216-1225.

35. Kocabas, F., Xie, L., Xie, J., Yu, Z., DeBerardinis, R.J., Kimura, W., Thet, S., Elshamy, A.F., Abouellail, H., Muralidhar, S., Liu, X., Chen, C., Sadek, H.A., Zhang, C.C., and Zheng, J. (2015). Hypoxic metabolism in human hematopoietic stem cells. Cell Biosci. 5, 39.

36. Zheng, J., Lu, Z., Kocabas, F., Böttcher, R.T., Costell, M., Kang, X., Liu, X., Deberardinis, R.J., Wang, Q., Chen, G.Q., Sadek, H., and Zhang, C.C. (2014). Profilin 1 is essential for retention and metabolism of mouse hematopoietic stem cells in bone marrow. Blood. 123, 992-1001.

37. Fan, X., Shi, P., Dai, J., Lu, Y., Chen, X., Liu, X., Zhang, K., Wu, X., Sun, Y., Wang, K., Zhu, L., Zhang, C.C., Zhang, J., Chen, G.Q., Zheng, J.*, and Liu, J. (2014). Paired immunoglobulin-like receptor B regulates platelet activation. Blood. 124, 2421-2430.

38. 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, G.F., Jiang, Y., Arase, H., and Zhang, C.C. (2014). A motif in LILRB2 critical for Angptl2 binding and activation. Blood. 124, 924-935.

39. Zheng, J., Umikawa, M., Cui, C., Li, J., Chen, X., Zhang, C., Huynh, H., Kang, X., Silvany, R., Wan, X., Ye, J., Cantó, A.P., Chen, S.H., Wang, H.Y., Ward, E.S., and Zhang, C.C. (2012). Inhibitory receptors bind ANGPTLs and support blood stem cells and leukaemia development. Nature. 485, 656-660.

40. Kocabas, F. #, Zheng, J. #, Thet, S., Copeland, N.G., Jenkins, N.A., DeBerardinis, R.J., Zhang, C., and Sadek, H.A. (2012). Meis1 regulates the metabolic phenotype and oxidant defense of hematopoietic stem cells. Blood. 120, 4963-4972. (#, co-first author)

41. 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

42. 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

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

44. 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)

45. 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

46. 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)

47. 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)

48. 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)

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