2004 - 2007  Institute of Biophysics, Chinese Academy of Sciences, Ph.D.

2008 - 2010  UC Berkeley, Postdoctoral fellow

2010 - 2015  Cornell University, Research Associate

2015 - 2016  Duke University, Senior Research Scientist

2016 -           Institute of Biophysics, Chinese Academy of Sciences, Professor

Non-coding RNAs (ncRNAs) such as microRNAs and long non-coding RNAs (lncRNAs) occupy the bulk of the genome, but their functions are often obscure. Global dysregulation of microRNAs and lncRNAs in cancers have been consistently reported, though ncRNA deletions often generate no phenotypes in normal tissue homeostasis. Why does the genome devote the bulk of its content to such "dark matter" that performs no function under normal physiology, and why do they become more important in cancer? What are the ncRNA associated proteins? Can we treat cancers by targeting ncRNA associated proteins?

Stem cells and differentiated cells have distinct behaviors. Growing evidences showed that changes in energy balance and metabolic status are critical for stem cells. However, many questions are still unclear. For example, how does metabolism regulate intestine/colon homeostasis and regeneration? How does metabolism impact colon cancer initiation and metabolism? Does dietary change benefit colon cancer prevention and therapy?

Growing from a single stem cell, intestine/colon organoid can form mini-gut structure, containing stem cells and all the progenies, which makes it a useful model for basic research and clinical applications, especially for biomarker identification and drug screening.

Our research is attempting to identify novel biomarkers, especially druggable ncRNAs and metabolic enzymes targeting colon cancer initiation and metastasis. We are developing organoids and mouse models for drug screening and mechanism study.

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.

(From Pengcheng Bu, March 5, 2024)