羅云萍
羅云萍教授,醫學(xué)博士,畢業(yè)于重慶醫科大學(xué),美國Scripps 研究中心博士后,現任中國醫學(xué)科學(xué)院/北京協(xié)和醫學(xué)院協(xié)和學(xué)者特聘教授、博士生導師。
共有30余篇研究論文發(fā)表國際優(yōu)秀學(xué)術(shù)雜志上。先后主持多項國家級重點(diǎn)基金的支助,其中包括國家重大科學(xué)研究計劃(973) , 國家自然科學(xué)基金等;
三次獲得美國腫瘤協(xié)會(huì )的獎勵。
電話(huà):69156475
Email:ypluo@ibms.pumc.edu.cn;yunpingluo@hotmail.com
組內人員:工作人員:斯琴 大專(zhuān),
主管技師; 陳翀 博士,助理研究員
研究興趣和方向:
課題組研究方向集中在腫瘤免疫逃逸機制,機體免疫系統與腫瘤發(fā)生的關(guān)系以及腫瘤的基因和免疫治療的基礎及應用研究研究特色與成果
1.
腫瘤微環(huán)境與腫瘤形成的關(guān)系及基因疫苗研究。
研究腫瘤微環(huán)境中的免疫細胞,如腫瘤相關(guān)的巨噬細胞(TAMs)與腫瘤細胞的相互作用以及與腫瘤發(fā)生,浸潤和轉移的關(guān)系,從中發(fā)現有效的基因或免疫治療的方法。已建立了一系列以抗腫瘤細胞,抗腫瘤新生血管生長(cháng)以及調節腫瘤微循環(huán)的基因和免疫疫苗,并在疫苗的設計以及佐劑的應用上有大膽的創(chuàng )新。
(1)腫瘤相關(guān)抗原Fra-1/IL-18多功能聯(lián)合基因疫苗應用于預防和治療小鼠乳腺癌和直腸癌的研究。該研究成果2003年獲得美國腫瘤學(xué)會(huì )獎勵(AACR-Inglenook
Vineyards Scholar-in-Training Award)。論文發(fā)表在PANS和 Cancer Research 。
(2)腫瘤相關(guān)巨噬細胞為靶細胞的調節腫瘤生長(cháng)微環(huán)境的基因疫苗的研究,構建了以L(fǎng)egumain為靶基因
的DNA疫苗清除浸潤進(jìn)人腫瘤組織中的TAM。重建了腫瘤微環(huán)境,使腫瘤細胞向良性分化,減少了腫瘤細胞的轉移。本研究得到了高度評價(jià),2005年獲得美國癌癥學(xué)會(huì )獎勵(AACR-Glaxo
Smith Kline Outstanding Clinical Scholar Awards)。相關(guān)論文發(fā)表在JCI,
(2006,并在當期的Highlight中作特別介紹)(Cancer Research和CII) 。
2.腫瘤干細胞與腫瘤微環(huán)境中腫瘤相關(guān)巨噬細胞(TAMs)相互作用的研究。
腫瘤微環(huán)境對腫瘤細胞的作用是腫瘤研究的重要領(lǐng)域,我們首先提出
TAMs可能是腫瘤干細胞的Niche,對腫瘤干細胞功能的維持發(fā)揮支持和調節作用。
(1)在首先發(fā)現TAM對CSC中
EGF-R/STAT3/SOX2高表達信號轉導通路異常調節的基礎上,系統的分析TAMs與腫瘤干細胞相互作用促進(jìn)腫瘤細胞生長(cháng)和轉移的分子基礎。這一發(fā)現對研究腫瘤微環(huán)境與腫瘤干細胞的關(guān)系的基礎及臨床應用研究具有重要的意義,
文章發(fā)表后得到同行積極的反應。 2010年獲得美國癌癥學(xué)會(huì )獎勵AACR Susan G. Komen Scholar in Training Award,
相關(guān)論文發(fā)表在BJC; Stem cell,。
(2)研究發(fā)現TAMs中高表達Fra-1轉錄因子和IL-6/Stat3信號轉導通路,而高表達的Fra-1與激活的
IL-6/Stat3信號轉導通路高度相關(guān)。(Oncogene,2010,引用
34次)進(jìn)一步,我們找到一種microRNA即miR-19a-3p,它是一種在腫瘤相關(guān)巨噬細胞受腫瘤微環(huán)境刺激并向M2型極化過(guò)程中表達受明顯抑制,miR-19a-3p在抑制TAM向M2型極化過(guò)程中起關(guān)鍵性作用,而腫瘤微環(huán)境通過(guò)分泌IL-6來(lái)抑制miR-19a-3p的表達來(lái)促進(jìn)TAM的M2極化,從而促進(jìn)腫瘤的發(fā)展和轉移。這一結論為利用miRNA調控了腫瘤微環(huán)境提供了理論依據。(Oncogene;2013)。
論文發(fā)表:
1.Chen C, Cao F, Bai L, 2, Liu Y,
2, Xie J, Wang W, Si Q, Yang J, Chang A, Liu D, Liu D, Chuang TH, Xiang R and Luo Y*, IKKβ enforces a LIN28B/TCF7L2 positive feedback
loop that promotes cancer cell stemness and metastasis, Cancer
Res, 2015, 75(8): 1725-1735
2. Yang J, Chen C, Liu Y, Si Qin,
Chuang TH, Reisfeld RA, Xiang R, Luo Y, MicroRNA-19a-3p
inhibits breast tumor metastasis and progression by inducing Macrophage
polarization through down-regulating the expression of Fra-1 gene. Oncogene. 2013 Jul 8. doi: 10.1038/onc.2013.258.
3. Yang J, Liao D, Chen C, Liu Y , Chuang TH, Xiang R, Markowitzb D,
Reisfeld RA, Luo Y . Tumor
associated macrophages regulate murine breast cancer stem cells through a novel
paracrine EGFR/Stat3/Sox-2 signaling pathway. Stem
cell 2013 Feb;31(2):248-58. doi: 10.1002/stem.1281
4. Xiang R,
Liao D , Cheng TM, Zhou H, Chung TH, Markowitz D, Reisfeld RA, Luo
Y, Knockdown of transcription factor Sox2 in cancer stem cells
suppresses metastasis of murine non-small cell lung cancer cells. Br
J Cancer. 2011 26;104(9):1410-7.
5.Xu C, Liu J, Hsu LC, Luo Y, Xiang R, Chuang TH. Functional interaction of
Hsp90 and Beclin 1 modulates Toll-like receptor-mediated autophagy. FASEB J. 2011 4.
6. Qian BJ, Yan F, Li N, Liu QL,
Lin YH, Liu CM, Luo Y, Guo F, Li HZ. MTDH/AEG-1-based
DNA vaccine suppresses lung metastasis and enhances chemosensitivity to
doxorubicin in breast cancer. Cancer Immunol
Immunother. 2011;60(6):883-93.
7. Liao D, Liu Z,
Wrasidlo W, Chen T, Luo Y, Xiang R, Reisfeld RA.
Synthetic enzyme inhibitor: a novel targeting ligand for nanotherapeutic drug
delivery inhibiting tumor growth without systemic toxicity. Nanomedicine. 2011 17.
8.Liao D, Luo
Y, Markowitz, Xiang R Reisfeld RA. Cancer Associated Fibroblast
Promote tumor growth and metastasis by modulating the tumor immune
microenvironment in a 4T1 murine breast cancer model. PLoS
ONE. 2010;4(11) e7965
9. Luo Y, Zhou
H, Krueger J, Kaplan C, Liao D, Markowitz D, Liu C, Chen T, Reisfeld RA and
Xiang R. Transcriptional regulation of tumor-associated macrophages (TAMs)
controls invasion, angiogenesis and metastasis of breast cancer cells. Oncogene. 2010 4;29(5):662-73.
10. Lee J, Hayash
M, Lo JF, Fearns C, Chu WM, Luo Y, Xiang R, Chuang TH.
NF-kB activation primes cells to a pro-inflammatory polarized response to a TLR7
agonist. Biochem J.
2009;421(2):301-310
11. Liu J, Xu C, Hsu LC, Luo Y, Xiang R, Chuang TH. A five-amino-acid motif in the
undefined region of the TLR8 ectodomain is required for species-specific ligand
recognition. Mol Immunol. 2010;47(5):1083-90.
12.Xiang R, Luo Y, Niethammer AG, Reisfeld RA. Oral
DNA vaccines target the tumor vasculature and microenvironment and suppress
tumor growth and metastasis. Immunol Rev. 2008;
222:117-28
13. Lewēn S, Zhou H, Hu HD, Cheng TM, Markowitz D, Reisfeld
RA, Xiang R and Luo Y. A Legumain-based minigene vaccine
targets the tumor stroma and suppresses breast cancer growth and angiogenesis. Cancer Immunol Immunother. 2008; 57(4):507-15
14.Luo Y, Dorothy Markowitz, Rong Xiang, He
Zhou and Ralph A.
Reisfeld. FLK-1-based minigene vaccines induce T
cell-mediated suppression of angiogenesis and tumor protective immunity in
syngeneic BALB/c mice. Vaccine 2007 9; 25(8): 1409-15
15. Jiali Li, Sonya Lad, Guang Yang, Luo Y, Milena
Iacobelli-Martinez, F. James Primus, Ralph A. Reisfeld, and Erguang Ll. Adenovirus fiber shaft contains a
trimerization element that supports peptide fusion for targeted gene delivery. J Virol. 2006; 80(24):12324-31.
16. Luo
Y, Zhou, H., Kaplan CD., Kruger JA, Lee SH, Xiang R, Reisfeld RA.
Induction of tumor-specific T cell memory by a DNA vaccine targeting Fos-related
Antigen 1. J Clin Invest 2006;116(8):2132-2141.
17.
Kruger JA, Kaplan CD, Luo Y , Zhou H, Markowitz D, Xiang
R, Reisfeld RA. Novel Model fro the In Vivo Study of Stem Cell Like Cancer Cells
in Immune Competent Mice. Blood, 2006
1;108(12):3906-12.
18. Kaplan CD, Kruger JA, Zhou, H, Luo
Y, Xiang R, Reisfeld RA. Anovel DNA vaccine encoding PDGFRb
suppresses growth and dissemination of murine colon, lung and breast carcinoma. Vaccine 2006 17;24(47-48):6994-7002.
19. Lee SH,
Mizutani M, Mizutani N, Luo Y, Zhou, H, Kaplan CD, Xiang
R, Reisfeld RA. Endoglin(CD105) is a Target for an oral DNA Vaccine against
breast cancer. Cancer Immunol and Immunotherapy 2006;55(12):1565-74.
20. Luo Y, Wu WY, Sun CZ,
Liu Y, Kuo P, Varga J, Xiang R, Reisfeld R, Kim D, Thomas J, Edgington S, Liu C.
Targeting Cell-Impermeable Prodrug Activation to Tumor Microenvironment
Eradicates Multiple Drug-Resistant Neoplasm. Cancer Res.
2006 66: 970-980.
21. Zhou H, Luo Y, Kaplan CD,
Kruger JA, Lee SH, Xiang R, Reisfeld RA. A DNA-based cancer vaccine enhances
lymphocyte crosstalk by engaging the NKG2D receptor. Blood 2005 107(8):3251-57.
22. Luo Y, Zhou H,
Mizutani M, Mizutani N, Xiang R, Reisfeld R. A DNA vaccine targeting
Fos-related antigen 1 enhanced by IL-18 induces long-lived T-cell memory against
tumor recurrence. Cancer Research. 2005 15;
65(8):3419-27.
23. Zhou H, Luo Y, Kaplan CD,
Kruger JA, Lee SH, Xiang R, Reisfeld RA. DNA-based vaccines activate innate and
adaptive anti-tumor immunity by engaging the NKG2D receptor. Proc
Natl Acad Sci U S A. 2005 2; 102(31):10846-51.
24. Zhou H, Luo Y , Mizutani M, Mizutani N, Reisfeld RA Xiang R. T
cell-mediated suppression of angiogenesis results in tumor protective immunity. Blood 2005 Sep 15;106 (6):2026-32.
25. Rong Xiang
R, Mizutani N, Luo Y, Chiodini C, Zhou H, Mizutani M, Ba
Y, Becker JC, Reisfeld RA. A DNA Vaccine Targeting Survivin Combines Tumor Cell
Apoptosis with Suppression of Angiogenesis in the Eradication of Lung Tumor
Metastases. Cancer Research 2005 15;
65(2):553-61.
在研課題:
1. 國家重大科學(xué)研究計劃(973):
腫瘤干細胞在實(shí)體腫瘤發(fā)展中的調控機制的研究--腫瘤免疫微環(huán)境在腫瘤發(fā)展中對CSC的調控機制。項目編號2013CB967202;起止時(shí)間:2013-2017年
2. 自然科學(xué)基金(重大研究計劃):
非可控性炎性微環(huán)境對腫瘤干細胞轉錄網(wǎng)絡(luò )機制的調控及其新的治療策略的探索;項目編號91029734;起止時(shí)間:2011-2013年
3. 自然科學(xué)基金(面上項目):“再教育”腫瘤相關(guān)巨噬細胞重建腫瘤免疫微環(huán)境-基于靶向調節Fra-1信號轉導通路的免疫治療;
項目編號30671938;起止時(shí)間:2011-2013年