表观遗传调控与干预重点实验室

1997 - 2001  大连工业大学，工学学士 

2001 - 2004  大连理工大学，工学硕士

2004 - 2007  中科院生物物理研究所，理学博士

2008 - 2010  美国加州大学伯克利分校，博士后

2010 - 2015  美国康奈尔大学，研究助理

2015 - 2016  美国杜克大学，资深科学家

2016 - 至今  中科院生物物理研究所，研究员

　　1. 非编码RNA在肿瘤发生发展中的功能和作用机制

　　肿瘤的发生和发展与非编码RNA调控失衡相关。我们首次发现非编码RNA在肠癌干细胞分裂中不对称地分布在两个子细胞中，决定子细胞命运，进而发现非编码RNA不对称分布调控肠上皮稳态和肠癌地发生。我们将致力于研究非编码RNA对肿瘤发生、转移，细胞命运和细胞代谢的影响。

　　2. 细胞代谢对肿瘤发生、转移及干细胞命运的影响

　　细胞代谢为细胞提供其生长所需能量和生物合成的原料。理解细胞在在不同生理和病理条件下的代谢机理，进而改变其代谢途径是疾病治疗的新靶点。课题组将结合代谢组学，转录组学和小鼠模型研究细胞代谢对肿瘤的发生、转移，干细胞分裂、更新和分化的影响。

　　3. 基于类器官培养的疾病靶基因鉴定和药物筛选

　　类器官（Organoids）是由干细胞在体外3D培养，形成从细胞组成和结构上能够模拟体内相应器官的培养体，是研究器官发育、肿瘤生成和个性化精准治疗的重要工具。将利用建立并利用类器官培养库鉴定疾病相关基因和筛选个性化药物。

1. Yan H, Bu P*. TAMC-derived creatine sustains glioblastoma growth. Cell Metabolism. 2024. 36(1):1-3

2. Wu Z^#, Zhang X^#, An Y, Xue Y, Ma K, Ye G, Zhang F, Qiao Y, Wu Y2,3, Du J, Chen Z, Zhu Z, Shi G, Wan M, Jiang B, Zhang P*, Liu J*, Bu P*. CLMP is a tumor suppressor that determines all-trans retinoic acid response in colorectal cancer. Developmental Cell. 2023. 58(23):2684-2699.

3. Chao S^#, Zhang F^#, Huiwen Yan#, Wang L, Zhang L, Wang Z, Wang J, Xue R, Wang L, Wu Z, Shi G, Xue Y, Du J*, Bu P*. Targeting intra-tumor heterogeneity suppresses colorectal cancer chemoresistance and metastasis. EMBO Reports. 2023. e56416. doi: 10.15252/embr.202256416.

4. Liu H^#, Du J^#, Chao S, Li S, Cai H, Zhang H, Chen G, Liu P, Bu P*. Fusobacterium nucleatum Promotes Colorectal Cancer Cell to Acquire Stem Cell-Like Features by Manipulating Lipid Droplet-Mediated Numb Degradation. Advanced Science. 2022. e2105222. doi: 10.1002/advs.202105222.

5. Zhang L, Zhu Z, Yan H, Wang W, Wu Z, Zhang F, Zhang Q, Shi G, Du J, Cai H, Zhang X, Hsu D, Gao P, Piao HL*; Chen G*; Bu P*. Creatine promotes cancer metastasis through activation of Smad2/3. Cell Metabolism. 2021. 33(6):1111-1123.

Highlighted in Cell Metabolism

6. Yan H^#, Wang Z^#, Sun Y, Hu L*, Bu P*. Cytoplasmic NEAT1 Suppresses AML Stem Cell Self-Renewal and Leukemogenesis through Inactivation of Wnt Signaling. Advanced Science. 2021. 8(22):e2100914.

7. Wu Z^#, Liu J^#, Chen G, Du J, Cai H, Chen X, Ye G, Luo Y, Luo Y, Zhang L, Duan H2, Liu Z2, Yang S, Sun H, Cui Y, Sun L, Zhang H, Shi G, Wei T, Liu P, Yan Y*, Feng J*, Bu P*. CD146 is a novel ANGPTL2 receptor that promotes obesity by manipulating lipid metabolism and energy expenditure. Advanced Science. 2021. 8(6):2004032.

8. Wang L^#, Wang E^#, Prado Balcazar J, Wu Z, Xiang K, Wang Y, Huang Q, Negrete M, Chen KY, Li W, Fu Y, Dohlman A, Mines R, Zhang L, Kobayashi Y, Chen T, Shi G, Shen JP, Kopetz S, Tata PR, Moreno V, Gersbach C, Crawford G, Hsu D, Huang E, Bu P*, Shen X*. Chromatin Remodeling of Colorectal Cancer Liver Metastasis is Mediated by an HGF-PU.1-DPP4 Axis. Advanced Science. 2021. 8(19):e2004673.

9. Wang X^#*, Liu C^#, Zhang S^#, Yan H, Zhang L, Jiang A, Liu Y, Feng Y, Li D, Guo Y, Hu X, Lin Y, Bu P, Li D*. N⁶-methyladenosine modification of MALAT1 promotes metastasis via reshaping nuclear speckles. Developmental Cell. 2021. 8;56(5):702-715.

10. Bu P^#*, Chen KY^#, Xiang K^#, Johnson C^#, Crown SB, Rakhilin N, Ai Y, Wang L, Xi R, Astapova I, Han Y, Li J, Barth BB, Lu M, Gao Z, Mines R, Zhang L, Herman M, Hsu D, Zhang GF, Shen X*. Aldolase B-Mediated Fructose Metabolism Drives Metabolic Reprogramming of Colon Cancer Liver Metastasis. Cell Metabolism. 2018. 27(6):1249-1262.

Highlighted in Nature Reviews Endocrinology

11. Wang L, Wang E, Wang Y, Mines R, Xiang K, Sun Z, Zhou G, Chen KY, Rakhilin N, Chao S, Ye G, Wu Z, Yan H, Shen H, Everitt J, Bu P*, Shen X*. miR-34a is a microRNA safeguard for Citrobacter-induced inflammatory colon oncogenesis. eLife. 2018. 7. pii: e39479. doi: 10.7554/eLife.39479.

12. Chen KY, Srinivasan T, Tung KL, Belmonte JM, Wang L, Murthy PKL, Choi J, Rakhilin N, King S, Varanko AK, Witherspoon M, Nishimura N, Glazier JA, Lipkin SM, Bu P*, Shen X*. A Notch positive feedback in the intestinal stem cell niche is essential for stem cell self-renewal. Molecular Systems Biology. 2017. 13(4):927.

13. Bu P^#*, Wang L^#, Chen KY, Srinivasan T, Murthy PK, Tung KL, Varanko AK, Chen HJ, Ai Y, King S, Lipkin SM, Shen X*. miR-34a and Numb synergize for asymmetric cell fate determination to control stem cell proliferation.  Cell Stem Cell. 2016. 18(2):189-202.

Highlighted in Cancer Discovery and AAAS

14. Wang L^#, Bu P^#, Ai Y, Srinivasan T, Chen HJ, Xiang K, Lipkin SM, Shen X*. A large non-coding RNA regulates colon cancer stem cell asymmetric division. eLife. 2016; 10.7554/eLife.14620.

15. Chen HJ^# Wei Z^#, Sun J, Bhattacharya A, Savage DJ, Serda R, Mackeyev Y, Curley SA, Bu P, Wang L, Chen S, Cohen-Gould L, Huang E, Shen X, Lipkin SM, Copeland NG, Jenkins NA*, Shuler ML*. A recellularized human colon model identifies cancer driver genes. Nature Biotechnology. 2016. 34(8):845-51.

16. Srinivasan T, Walters J, Bu P, Than EB, Tung KL, Chen KY, Panarelli N, Milsom J, Augenlicht L, Lipkin SM*, Shen X*. Notch signaling regulates asymmetric cell fate of fast- and slow-cycling colon cancer initiating cells. Cancer Research. 2016. 76(11):3411-21.

17. Bu P^#, Wang L^#, Chen KY, Rakhilin N, Sun J, Closa A, Tung KL, King S, Kristine Varanko A, Xu Y, Huan Chen J, Zessin AS, Shealy J, Cummings B, Hsu D, Lipkin SM, Moreno V, Gumus ZH, Shen X*. miR-1269 Promotes Metastasis through a Positive Feedback Loop with TGF-β. Nat communications. 2015. 6:6879.

18. Sun S, Shi G, Sha H, Ji Y, Han X, Shu X, Ma H, Inoue T, Gao B, Kim H, Bu P, Guber RD, Shen X, Lee AH, Iwawaki T, Paton AW, Paton JC, Fang D, Tsai B, Yates JR 3rd, Wu H, Kersten S, Long Q, Duhamel GE, Simpson KW, Qi L* IRE1α is an endogenous substrate of endoplasmic-reticulum-associated degradation. Naure Cell Biology. 2015. 17(12):1546-55.

19. Li J, Ai Y, Wang L, Bu P, Sharkey CC, Wu Q, Wun B, Roy S, Shen X, King MR*. Targeted drug delivery to circulating tumor cells via platelet membrane-functionalized particles. Biomaterials. 2015. 76:52-65.

20. Chen HJ, Sun J, Huang Z, Hou H Jr, Arcilla M, Rakhilin N, Joe DJ, Choi J, Gadamsetty P, Milsom J, Nandakumar G, Longman R, Zhou XK, Edwards R, Chen J, Chen KY, Bu P, Wang L, Xu Y, Munroe R, Abratte C, Miller AD, Gumus ZH, Shuler M, Nishimura N, Edelmann W, Shen X*, Lipkin SM*. Chemokine-Targeted Mouse Models of Human Primary and Metastatic Colorectal Cancer. Nature Biotechnology. 2015. 33(6):656-60.

21. Okada N, Lin CP, Ribeiro MC, Biton A, Lai G, He X, Bu P, Vogel H, Jablons DM, Keller AC, Wilkinson JE, He B, Speed TP, He L*. A positive feedback between p53 and miR-34 miRNAs mediates tumor suppression. Genes & Develop. 2014. 28: 438-450

22. Bu P, Chen KY, Chen JH, Wang L, Walters J, Shin YJ, Goerger JP, Sun J, Witherspoon M, Rakhilin N, Li J, Yang H, Milsom J, Lee S, Zipfel W, Jin MM, Gümü? ZH, Lipkin SM*, Shen X*. A microRNA miR-34a-Regulated Bimodal Switch Targets Notch in Colon Cancer Stem Cells. Cell Stem Cell. 2013. 12(5):602-625.

Highlighted in Cell Stem Cell and Biotechniques

23. Chen HJ, Edwards R, Tucci S, Bu P, Milsom J, Lee S, Edelmann W, Gümüs ZH, Shen X*, Lipkin S*. The chemokine 25 and chemokine receptor 9 axis suppresses colon cancer invasion and metastasis. Journal of Clinical Investigation. 2012. 122(9):3184-96

24. Choi YJ^#, Lin CP^#, Ho JJ, He X, Okada N, Bu P, Zhong Y, Kim SY, Bennett MJ, Chen C, Ozturk A, Hicks GG, Hannon GJ, He L*. miR-34a miRNAs provide a barrier for somatic cell reprogramming. Nature Cell Biology. 2011. 13(11):1353-60.

25. Bu P, Zhuang J, Feng J, Yang D, Shen X, Yan X*. Visualization of CD146 dimerization and its regulation in living cells. BBA-Molecular Cell Research. 2007. 1773(4):513-20.

26. Bu P, Gao L, Zhuang J, Feng J, Yang D, Yan X*. Anti-CD146 monoclonal antibody, AA98, inhibits angiogenesis via suppression of NF-kB activation. Molecular Cancer Therapy. 2006. 5(11): 2872-2878

邀请综述

1. Chao S^#, Yan H^#, Bu P*. Asymmetric division of stem cells and its cancer relevance. Cell Regeneration. 2024.13(1):5.

2. Zhang L, Bu P*. The Two Sides of Creatine in Cancer. Trends in Cell Biology. 2021. S0962-8924(21)00230-0. doi: 10.1016/j.tcb.2021.11.004.

3. Yan H, Bu P*. Non-coding RNAs in cancer. Essays in Biochemistry. 2021. 5(4):625-639.

4. Yan H, Bu P*. Non-coding RNAs in cancer stem cells. Cancer Letters. 2018. 421:121- 126.

（资料来源：卜鹏程研究员，2024-03-05）