個(gè)人簡(jiǎn)介：
2008年畢業(yè)于山西師范大學(xué)獲得生物學(xué)學(xué)士學(xué)位，2014年畢業(yè)于香港中文大學(xué)獲得化學(xué)病理學(xué)博士學(xué)位，并于2015-2019年先后在美國(guó)Fred Hutch癌癥研究中心和香港大學(xué)醫(yī)學(xué)院任職博士后,，2019年10月通過(guò)中山大學(xué)高層次人才計(jì)劃加入中山大學(xué)附屬第七醫(yī)院,。主持或已完成國(guó)家,、省市級(jí)科研項(xiàng)目共6項(xiàng)（含國(guó)家自然科學(xué)基金3項(xiàng)）,。以第一/通訊作者發(fā)表研究論文共20篇,，研究成果主要發(fā)表在Gastroenterology,、Genes and Development,、Cell Death and Disease、Drug Resistance Updates,、Oncogene及Cellular and Molecular Life Sciences等雜志上,，并擔(dān)任Advanced Science、JCI Insight,、Cellular and Molecular Life Sciences,、International Journal of Biological Sciences、Cancer Letters等雜志審稿人,。
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主要研究方向與成果:
（1）iPSC誘導(dǎo)分化的類器官模型在神經(jīng)系統(tǒng)疾病重塑和致病機(jī)制研究中的應(yīng)用,。
先天性巨結(jié)腸癥（HSCR）是一種復(fù)雜的腸神經(jīng)系統(tǒng)發(fā)育缺陷的遺傳病,。（1）我們通過(guò)全基因組測(cè)序篩選首次報(bào)道了BACE2功能缺失突變?yōu)?/span>HSCR的新致病因素，并利用病人iPSC誘導(dǎo)分化的腸神經(jīng)嵴細(xì)胞（ENCC）模型闡明了BACE2介導(dǎo)的APP蛋白切割失衡是誘發(fā)腸神經(jīng)細(xì)胞凋亡的新致病機(jī)制（Gastroenterology, 2018; Featured comments by Heuckeroth TO Gastroenterology, 2018）,。該研究發(fā)現(xiàn)為BACE2功能缺失HSCR病人的臨床診斷和治療提供了新靶點(diǎn),。（2）基于iPSC誘導(dǎo)分化的ENCC及結(jié)直腸類器官模型，建立了可在體內(nèi)外模擬ENCC分化,，成熟及其支配結(jié)腸類器官蠕動(dòng)等神經(jīng)生理過(guò)程的3D模型（Gastroenterology, 2019）,。該研究發(fā)現(xiàn)為我們?cè)隗w內(nèi)外驗(yàn)證HSCR相關(guān)的致病基因，重塑HSCR病人相關(guān)的病理特征,，以及致病機(jī)制研究和藥物篩選等轉(zhuǎn)化工作提供了一個(gè)近乎人體微環(huán)境的3D模型,。（3）基于iPSC誘導(dǎo)分化的腦類器官模型，闡明了BACE2介導(dǎo)的APP蛋白切割失衡是HSCR-AD共同的致病機(jī)制（Cell Death Discovery, 2022,；Cell and Bioscience, 2021）,。該研究發(fā)現(xiàn)證明了腸腦神經(jīng)系統(tǒng)疾病在發(fā)病機(jī)制和病理特征等方面存在非常高的相似性，為腸腦關(guān)聯(lián)神經(jīng)系統(tǒng)疾病的診斷和治療等提供了新思路,。
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（2）Hippo-YAP信號(hào)通路在腫瘤發(fā)生發(fā)展及腫瘤微環(huán)境重塑中的作用及分子機(jī)制研究,。
YAP (Yes-Associated Protein) 是Hippo信號(hào)通路的下游效應(yīng)因子。作為一個(gè)轉(zhuǎn)錄共調(diào)節(jié)因子,，該蛋白過(guò)表達(dá)或者激活參與到腫瘤發(fā)生發(fā)展,、轉(zhuǎn)移、治療耐藥以及腫瘤微環(huán)境重塑等多個(gè)過(guò)程中,。（1）上皮細(xì)胞連環(huán)蛋白（αE-catenin）缺失可誘導(dǎo)腫瘤發(fā)生,，我們研究發(fā)現(xiàn)αE-catenin可通過(guò)抑制Integrinβ4-SRC-YAP信號(hào)通路的激活，從而發(fā)揮其抑癌作用,。在該信號(hào)通路終端,，由激酶SRC介導(dǎo)的YAP酪氨酸位點(diǎn)磷酸化才是αE-catenin缺失誘導(dǎo)腫瘤發(fā)生的真正原因（Genes and Development, 2016）。該研究成果闡明了αE-catenin缺失誘導(dǎo)腫瘤發(fā)生的新機(jī)制,，為該類腫瘤靶向治療提供了新思路,。該研究成果多次被Nature、Cell,、Cell Stem Cell等頂級(jí)雜志進(jìn)行引用和論述,，并兩次被世界學(xué)術(shù)組織F1000正面評(píng)論并列為推薦閱讀論文。（2）進(jìn)一步研究還發(fā)現(xiàn)SRC激活介導(dǎo)的YAP酪氨酸位點(diǎn)修飾誘導(dǎo)了YAP/TEAD與轉(zhuǎn)錄因子KLF5或TFAP2A等轉(zhuǎn)錄復(fù)合體的形成以及下游靶基因的轉(zhuǎn)錄,，并促進(jìn)了三陰乳腺癌的干性和轉(zhuǎn)移潛能（Cellular and Molecular Life Sciences, 2023）,，以及HER2+乳腺癌對(duì)曲妥珠單抗治療的耐藥（Drug Resistance Updates, 2024）,。（3）研究還證實(shí)YAP是RNA結(jié)合蛋白復(fù)合體LIN28/MSI2誘導(dǎo)三陰乳腺癌腫瘤干性和轉(zhuǎn)移的關(guān)鍵效應(yīng)分子,，因此靶向YAP依賴的轉(zhuǎn)錄輸出有望成為治療該類三陰乳腺癌的新靶點(diǎn)（Oncogene, 2022）。
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主要科研論文：
1. Zou, H., Luo, J., Guo, Y., Deng, L., Zeng, L., Pan, Y., Li, P. Tyrosine phosphorylation-mediated YAP1-TFAP2A interactions coordinate transcription and trastuzumab resistance in HER2+ breast cancer. Drug Resistance Updates (2024), 73:101051.
2. Tong, T., Huang, M., Yan, B., Lin, B., Yu, J., Teng, Q., Li, P*., Pang, J*. Hippo signaling modulation and its biological implications in urological malignancies. Molecular Aspects of Medicine (2024), 98:101280. (* Co-corresponding author).
3. Luo, J., Deng, L., Zou, H., Guo, Y., Tong, T., Huang, M., Ling, G., Li, P. New insights into the ambivalent role of YAP/TAZ in human cancers. Journal of Experimental and Clinical Cancer Research (2023), 42(1):130.
4. Zou, H., Luo, J., Guo, Y., Tong, T., Liu, Y., Chen, Y., Xiao, Y., Ye, L., Zhu, C., Deng, L., Wang, B., Pan, Y., Li, P. Tyrosine kinase SRC-induced YAP1-KLF5 module regulates cancer stemness and metastasis in triple-negative breast cancer. Cellular and Molecular Life Sciences (2023), 80(2):41.
5. Luo, J., Zou, H., Guo, Y., Tong, T., Chen, Y., Xiao, Y., Pan, Y., Li, P. The oncogenic roles and clinical implications of YAP/TAZ in breast cancer. British Journal of Cancer (2023), 128(9):1611-1624.
6. Luo, J., Zou, H., Guo, Y., Tong, T., Ye, L., Zhu, C., Deng, L., Wang, B., Pan, Y., Li, P. SRC kinase-mediated signaling pathways and targeted therapies in breast cancer. Breast Cancer Research (2022), 24(1):99.
8. Zou, H., Luo, J., Guo, Y., Liu, Y., Wang, Y., Deng, L., Li, P. RNA-binding protein complex LIN28/MSI2 enhances cancer stem cell-like properties by modulating Hippo-YAP1 signaling and independently of Let-7. Oncogene (2022), 41(11): 1657-1762.
10. Luo, J., Zou, H., Guo, Y., Huang, K., Ngan, ESW., Li, P. BACE2 variant identified from HSCR patient causes AD-like phenotypes in hPSC-derived brain organoids. Cell Death Discovery (2022), 8(1):47.
11. Luo, J., Li, P. Human pluripotent stem cell-derived brain organoids as in vitro models for studying neural disorders and cancer. Cell and Bioscience (2021), 11(1): 99.
12. Luo, J., Zou, H., Deng, L., Sun, X., Yuan, P., Li, P. Lin28 inhibits the differentiation from mouse embryonic stem cells to glial lineage cells through upregulation of Yap1. Stem Cells International (2021), 2021: 6674283.
13. Tang, C#., Li, P#., Lai, F., Fu, A., Lau, S., So, M., Lui, K., Li, Z., Zhuang, X., Yu, M., Liu, X., Ngo, N., Miao, X., Zhang, X., Yi, B., Tang S., Sun, X., Zhang, F., Liu, H., Liu, Q., Zhang, R., Wang, H., Huang, L., Dong, X., Tou, J., Cheah, K., Yang, W., Yuan, Z., Yip, Y., Sham, P., Tam, P., Garcia-barcelo, M., Ngan, E. Identification of genes associated with Hirschsprung disease, based on whole-genome sequence analysis, and potential effects on enteric nervous system development. Gastroenterology (2018), 155, 1908-1922. (# Co-first author).
14. Li, P#., Silvis, M#., Honaker, Y#., Lien, W.H., Arron, S., Vasioukhin, V. αE-catenin inhibits a novel Src-YAP1 oncogenic module that couples tyrosine kinases and the effector of Hippo signaling pathways. Genes and Development (2016), 30, 798-811. (# Co-first author).
15. Li, P., Ma, X., Adams, I.R., Yuan, P. A tight control of Rif1 by Oct4 and Smad3 is critical for mouse embryonic stem cell stability. Cell Death and Disease (2015) 6, e1588.
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合作研究機(jī)會(huì)：
本實(shí)驗(yàn)室長(zhǎng)期招收具有生物學(xué)或基礎(chǔ)醫(yī)學(xué)背景的碩,、博士研究生,，也非常歡迎有博士后合作意向的專職研究人員加盟,，一起探討生命的奧秘、并努力為改善人類的健康做出努力,，貢獻(xiàn)激情,。博士后研究人員可根據(jù)中山大學(xué)附屬第七醫(yī)院的要求獲得極具競(jìng)爭(zhēng)力的個(gè)人待遇、工作環(huán)境和長(zhǎng)遠(yuǎn)發(fā)展機(jī)會(huì),。
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個(gè)人郵箱:
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