鄭俊克

血液干細胞代謝調(diào)控和免疫靶向組

電話：021-63846590-776915

郵箱：[email protected]

鄭俊克課題組近幾年的研究揭示了骨髓微環(huán)境中造血干細胞代謝學特性及其與干性維持間的重要關系，特別是造血干細胞獨特的糖/氨基酸等代謝方式及其調(diào)控網(wǎng)絡,；同時闡明了微環(huán)境重要成分Angptls/APOE及其免疫抑制性受體LILRBs/JAM3等在體內(nèi)外維持造血干細胞干性的分子機制，以及在疾病狀態(tài)下白血病干細胞干性維持中的調(diào)控規(guī)律和潛在免疫治療新靶點等,。這些研究為發(fā)展造血干細胞體外擴增新技術及其臨床應用,，尋找靶向白血病干細胞的特異免疫治療靶點以更有效地治療白血病，提供了有力的條件,。

目前本團隊以造血干細胞/白血病干細胞代謝平臺為支持,，結(jié)合動物模型、代謝組學,、代謝感受器,、骨髓微環(huán)境成像和免疫治療（抗體和CAR-T）等相關前沿技術，聚焦于三個主要研究方向：1）造血干細胞和白血病干細胞糖,、氨基酸等內(nèi)在代謝調(diào)控規(guī)律,；2）骨髓微環(huán)境組分調(diào)控造血干細胞穩(wěn)態(tài)和惡變規(guī)律；3）白血病免疫治療機制探討和策略開發(fā),。

鄭俊克,，上海交通大學醫(yī)學院，研究員,，國家杰青項目入選者,。2007年畢業(yè)于上海交通大學醫(yī)學院,；2007-2012年在美國西南醫(yī)學中心從事博士后工作；2012年6月起受聘于上海交通大學醫(yī)學院細胞分化和凋亡教育部重點實驗室,。主要從事造血干細胞干性維持的機制及其惡性轉(zhuǎn)化為白血病干細胞的規(guī)律研究,。近年來，圍繞血液干細胞代謝和微環(huán)境成分-免疫抑制性受體介導的信號通路在干性維持和免疫靶向中的作用和機制方面,，取得系列重要發(fā)現(xiàn),，并以通訊/共同通訊作者在Nature、Cell Metabolism（封面文章）,、JCI,、Blood、Leukemia,、EMBO J等著名雜志上發(fā)表論文13余篇,，目前累計發(fā)表論文50篇，他引1300余次,。所獲資助項目還包括基金委重點項目,、優(yōu)青、面上項目,、上海市優(yōu)秀青年學術帶頭人,、曙光計劃以及浦江人才計劃等。擔任中國生理學會血液專業(yè)委員會委員,、中國病理生理學會青年工作委員會秘書長,、中國細胞生物學學會細胞代謝分會委員等學術職務。獲上海市第十五屆銀蛇獎,、上海市五四青年獎章和吳孟超醫(yī)學青年基金獎等,。

1. H Dan^#, Sun G^#, Hao X^#, He X^# , Zheng Z, Chen C, Yu Z, Xie L, Ma S, Liu L, Zhou B O, Chen H*, Zheng J*, Cheng T*. ANGPTL2-containing small extracellular vesicles from vascular endothelial cells accelerate leukemia progression. J Clin Invest ,2020, in press (*,co-corresponding author)

2. 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

3. 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)

4. 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

5. Zhang LS, Kang X, Lu J, Zhang Y, Wu X, Wu G, Zheng J, Tuladhar R, Shi H, Wang Q, Morlock L, Yao H, Huang LJ, Maire P, Kim J, Williams N, Xu J, Chen C, Zhang CC, Lum L.Installation of a cancer promoting WNT/SIX1 signaling axis by the oncofusion protein MLL-AF9. EBioMedicine. 39:145-158, 2019

6. 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-corresponding author)

7. 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-corresponding author)

8. 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

9. 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

10. 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

11. 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

12. Dai J, Lu Y, Wang C, Chen X, Fan X, Gu H, Wu X, Wang K, Gartner TK, Zheng J, Chen G, Wang X, Liu J. Vps33b regulates Vwf-positive vesicular trafficking in megakaryocytes. J Pathol. J Pathol., 240(1):108-19, 2016

13. 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

14. 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

15. Xia F, Wang N, Han B, Li Q, Chen Y, Zhu C, Chen Y, Pu X, Cang Z, Zhu C, Lu M, Meng Y, Guo H, Chen C, Lin D, Zheng J, Kuang L, Tuc W, Li B, Hu L, Shen Z, Lu Y. Hypothalamic-Pituitary-Gonadal Axis in Aging Men and Women: Increasing Total Testosterone in Aging Men. Neuroendocrinology, 104(3):291-301, 2017

16. 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-corresponding author)

17. 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

18. Shen J, Zheng J, Saxena R, Zhang CC, Tang L. Novel source of human hematopoietic stem cells from peritoneal dialysis effluents. Stem Cell Res, 15(2): 299-304, 2015

19. 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-corresponding author)

20. 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-corresponding author)

21. 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

22. Wang Q, Zhou Z, Zheng Y, Zheng J, Zhang CC. Relationship Between the Structural Specialties and Morphologies Based on a Group of Luminescent Imidazole Derivatives with Sensing Properties. Sci Adv Mater, 6(6): 1133-1139, 2014

23. Chen X, Zheng J, Zou Y, Song C, Hu X, Zhang CC. IGF binding protein 2 is a cell-autonomous factor supporting survival and migration of acute leukemia cells. J Hematol Oncol., 8;6(1):72, 2013

24. 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

25. 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)

26. 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

27. 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

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

29. Zhang S, Yajima H, Huynh H, Zheng J, Callen E, Chen HT, Wong N, Bunting S, Lin YF, Li M, Lee KJ, Story M, Gapud E, Sleckman BP, Nussenzweig A, Zhang CC, Chen DJ, Chen BP. Congenital bone marrow failure in DNA-PKcs mutant mice associated with deficiencies in DNA repair. J.Cell.Biol., 193(3):295–305, 2011

30. Huynh H^#, Zheng J^#, Umikawa M, Silvany R, Xie XJ, Wu CJ, Holzenberger M, Wang Q, Zhang CC. Components of the hematopoietic compartment in tumor stroma and tumor-bearing mice. PLoS ONE, 6(3): e18054, 2011 (#, co-first author)

31. Huynh H, Zheng J, Umikawa M, Zhang C, Silvany R, Iizuka S, Holzenberger M, Zhang W, Zhang CC. IGF binding protein 2 supports the survival and cycling of hematopoietic stem cells. Blood, 118(12):3236-3243, 2011

32. 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)

33. Lou Z, Zhang CC, Tirado CA, Slone T, Zheng J, Zaremba CM, Oliver D, Chen W. Infantile mixed phenotype acute leukemia (bilineal and biphenotypic) with t(10;11)(p12;q23);MLL-MLLT10. Leuk Res., 34(8): 1107-1109, 2010

34. Huynh H, Iizuka S, Kaba M, Kirak O, Zheng J, Lodish HF, Zhang CC. Insulin-like growth factor-binding protein 2 secreted by a tumorigenic cell line supports ex vivo expansion of mouse hematopoietic stem cells. Stem Cells, 26(6): 1628-1635, 2008

35. 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

36. 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)

37. Sun F, Fang H, Li R, Gao T, Zheng J, Chen X, Ying W, Sheng HZ. Nuclear reprogramming: the zygotic transcription program is established through an "erase-and-rebuild" strategy. Cell Res., 17(2): 117-134, 2007

38. 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)

39. 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)

出版著作

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.

 目前團隊包括副研,、助研、技術員,、博士后,、博士和碩士研究生等共有15人，課題組積極營造團結(jié)互助,、銳意進取,、努力攻艱的實驗室氛圍，培養(yǎng)了多名優(yōu)秀青年科研人才,，大大提升了團隊科研水平,。副研究員入選基礎醫(yī)學院優(yōu)秀青年教師計劃，也獲得國家自然科學基金面上項目和上海市科委自然科學基金面上項目資助,；助理研究員獲得國家自然科學基金青年項目和上海市科委自然科學基金面上項目資助,；所指導的4名博士后中（3名已出站），1名獲得國家自然科學基金青年項目,，1名獲國家博士后創(chuàng)新人才計劃資助,，1名獲中國博士后科學基金面上項目（一等）資助；課題組精心為所有的指導研究生制定個性化培養(yǎng)計劃,，培養(yǎng)出了多名優(yōu)秀學生,。課題組已培養(yǎng)畢業(yè)碩士生1名和博士生9名（其中3名和4名分別在美國和中國從事博士后工作，2名博士后獲國家自然科學基金青年項目,，1名博士獲國家自然科學基金面上項目并晉升為副研究員）,；3名學生獲得國家獎學金，1名獲上海市優(yōu)秀畢業(yè)生,，1名獲中國科學院大學優(yōu)秀畢業(yè)生和院長優(yōu)秀獎,，2名獲上海交通大學優(yōu)秀博士論文；目前,，指導在讀博士生6名及碩士生1名,；指導的學生多次在國內(nèi)外學術會議口頭報告或墻報評比中獲獎,。