生物物理及結構生物學(xué)系介紹

學(xué)系簡(jiǎn)介

生物物理及結構生物學(xué)系是在原生物物理系基礎上成立的，原生物物理系組建于1959年。根據我國醫學(xué)科學(xué)發(fā)展的需要，教育部決定在中國協(xié)和醫科大學(xué)及北京醫科大學(xué)首先成立生物物理學(xué)這一新興的交叉學(xué)科。1960年系人員包括助研、實(shí)習研究員、研究生和技術(shù)員近十人，人員的學(xué)科涉及醫學(xué)、生物學(xué)、物理學(xué)、化學(xué)、數學(xué)、自動(dòng)控制和電子學(xué)。并在全國14個(gè)重點(diǎn)醫學(xué)院校招收生物物理專(zhuān)業(yè)班學(xué)生進(jìn)行培養。確立生物物理系的研究方向為用先進(jìn)的數學(xué)物理的理論方法和技術(shù)研究疾病和生命過(guò)程的機理。任務(wù)包括科研和教學(xué)兩個(gè)方面。科研主要集中在如下3個(gè)研究方向：1) 生物能學(xué)研究。主要通過(guò)核磁共振儀研究生物體內的能量變遷以及它與人類(lèi)某些疾病的相關(guān)性；2) 細胞超微結構與功能研究。重點(diǎn)研究正常與病理狀態(tài)下亞細胞水平與分子水平結構與功能特點(diǎn)；3) 生物大分子結構研究。主要是探索藥物的作用機制及為研制新的藥物提供理論依據。目前有3個(gè)研究方向：1）人乳頭瘤病毒（HPV）及HIV的相關(guān)研究，特別是HPV疫苗的研究，主要是利用各種生物技術(shù)研發(fā)各種預防性及治療性基因工程疫苗；開(kāi)展各種疫苗佐劑的研究，包括傳統的鋁佐劑、具有TLR刺激活性的新型小分子化合物佐劑、乳劑及新型復合佐劑等的研究；2）慢性疾病早期預警及其預后新技術(shù)新方法研究；3) 疾病相關(guān)蛋白質(zhì)折疊、組裝與調控。教學(xué)方面：生物物理學(xué)系承擔了北京協(xié)和醫學(xué)院基礎學(xué)院的研究生及本科生的的理論教學(xué)任務(wù)，包括八年制臨床醫學(xué)專(zhuān)業(yè)《生物物理學(xué)》和研究生《細胞生物基礎及超微結構的分子生物學(xué)》課程。生物物理學(xué)系于80年代初批準為碩士點(diǎn)，1993年批準為博士點(diǎn)，先后培養了碩士博士研究生近100名。

歷屆主任及學(xué)科帶頭人

孫宗棠教授、李昆教授、司靜懿教授、吳元德教授、宋國興教授、李智立教授。

教學(xué)工作

一、教學(xué)人員介紹

參與教學(xué)人員：李智立、許雪梅、王晨軒、張婷、張沫

二、學(xué)系承擔的主要課程及建設情況

課程名稱(chēng)：生物物理學(xué)

課程負責人：李智立  授課對象：醫學(xué)八年制

雙語(yǔ)化建設：部分教學(xué)PPT為雙語(yǔ)

教學(xué)方法與手段：PPT演示、講授及實(shí)驗室觀(guān)摩

考核評價(jià)方式：閉卷考試(70分）+ 平時(shí)成績(jì)（30分）

課程名稱(chēng)：細胞生物基礎及超微結構的分子生物學(xué)

課程負責人：許雪梅    授課對象：研究生

雙語(yǔ)化建設：英文PPT

教學(xué)手段與方法：PPT講授+電鏡室參觀(guān)實(shí)習

考核評價(jià)方式：閉卷考試

三、特色教學(xué)工作

《生物物理學(xué)》是臨床影像學(xué)和物理診療學(xué)等臨床診斷的基礎學(xué)科，她是臨床八年制和4+4試點(diǎn)班開(kāi)設的課程，本課程聘請了本領(lǐng)域著(zhù)名的教授講授相關(guān)的基礎理論及學(xué)科發(fā)展前沿，為醫學(xué)生在分子水平上認識疾病發(fā)生、發(fā)展提供了新的視角。

各課題組科研工作

一、李智立課題組

1. 課題組簡(jiǎn)介

研究方向：慢性疾病早期預警及其預后評估新技術(shù)新方法、標志物。主要利用現代生物分析技術(shù)和質(zhì)譜技術(shù)，以血清/血漿和組織為研究對象，建立慢性疾病相關(guān)蛋白質(zhì)和代謝物的分離分析新技術(shù)和新方法；探究慢性疾病發(fā)生早期的物質(zhì)基礎變化規律；篩選與慢性疾病發(fā)生、發(fā)展相關(guān)的標志物。已在近萬(wàn)例血液樣本中發(fā)現可以早期預警慢病發(fā)生的個(gè)體化免疫炎癥相關(guān)蛋白質(zhì)復合物譜；基于該個(gè)體化的復合物譜可以分區良性疾病與惡性腫瘤，其敏感性和特異性均優(yōu)于90%；基于該復合物譜可以個(gè)體化的監測腫瘤復發(fā)或耐藥性的產(chǎn)生。在蛋白糖基化水平上，已建立三種簡(jiǎn)單、經(jīng)濟和環(huán)境友好的完整糖肽的富集分離技術(shù)，已在3000余例血液樣本中發(fā)現可以個(gè)體化區分良性疾病與惡性疾病的糖基化修飾標志物。在代謝物水平上，發(fā)現一組可以監測腫瘤預后的個(gè)體化脂類(lèi)標志物。

2. 課題組負責人介紹

理學(xué)博士，博士生導師，2004年至今，中國醫學(xué)科學(xué)院基礎醫學(xué)研究所&北京協(xié)和醫學(xué)院教授；2001-2004年美國耶魯大學(xué)藥理系，Associate Research Scientist; 1998-2001在中國藥科大學(xué)作博士后研究，主要利用細胞膜技術(shù)結合液相色譜-質(zhì)譜聯(lián)用技術(shù)篩選中藥活性成分；1991-1995年在國防科工委化學(xué)計量一級站開(kāi)展標準物質(zhì)研究，工程、高級工程師；1998年在中國科學(xué)院長(cháng)春應用化學(xué)研究所獲得理學(xué)博士學(xué)位。

3. 課題組成員介紹

張沫，副研究，博士，E-mail：zhangmo234@126.com；電話(huà)：010-69156458

周巾煜，助理研究員，博士，E-mail: zjy9415@163.com；電話(huà)：010-69156458

李丹，技師，博士，E-mail: lidan50505@163.com；電話(huà)：010-69156458

4. 課題組主要科研項目

5. 課題組代表性論文

(1) Mo Zhang, Qing Wang, Yupin Xu, Lei Guo, Zhizhen Lai and Zhili Li*, Graphitic carbon nitride quantum dots as analytical probe for viewing sialic acid on the surface of cells and tissues, Analytica Chimica Acta, 2020, 1095,204-211.

(2) Dan Zhang, Xiaoou Li, Xiaofeng Liu, Yanmin Wang, Mo Zhang, Qin Wang, Tianjing Chen, Zhili Li*, Disease-specific IgG Fc glycosylation ratios as personalized biomarkers to differentiate non-small cell lung Cancer from benign lung diseases, Proteomics Clinical Applications,2020,14,1900016.

(3) Yunpeng Wu, Rui Zhou, Zhizhen Lai1, Wei Wang, Na Li, Yuying Du, Lei Guo, Yuming Qiu, Qing-Tao Wang*, and Zhili Li*，Monitoring novel modified hemoglobin using mass spectrometry contributes to accurate blood glucose management of the Han Chinese population, Clinica Chimica Acta, 2019, 489, 124-129.

(4) Tianjing Chen, Chengyan He, Mo Zhang, Xiaoou Li, Xiaofeng Liu, Yujie Liu, Dan Zhang, and Zhili Li*, Disease-specific haptoglobin-βchain N-glycosylation as biomarker to differentiate non-small cell lung cancer from benign lung diseases, Journal of Cancer, 2019, 10, 5628-5637.

(5) Y. H. Sun, J. Li, H. J. Shu, Z. L. Li, J. M. Qian, Serum immunoinflammation?related protein complexes discriminate between inflammatory bowel disease and colorectal cancer, Clinical and Translational Oncology, 2019, 21, 1680-1686.

(6)Yupin Xu, Mo Zhang, Qing Wang, Zhili Li*, In situ detecting changes in membrane lipid phenotypes of macrophages cultured in different cancer microenvironments using mass spectrometry, Analytica Chimica Acta, 2018, 1026, 101-108.

(7) Yujie Liu, Yunpeng Wu, Yanmin Wang, Mo Zhang, and Zhili Li*，Increased Levels of Serum Protein Complexes Are Associated with Type 2 Diabetes，International Journal of Medical Sciences, 2018, 15(3), 210-216.

(8) Mo Zhang, Yujie Liu, Dan Zhang, Tianjing Chen, Zhili Li*, Facile and Selective Enrichment of Intact Sialoglycopeptides Using Graphitic Carbon Nitride, Analytical Chemistry, 2017, 89(15) , 8064-8069.

(9) Shuai Guo, Dan Zhou, Mo Zhang, Tiejun Li, Yujie Liu, Yupin Xu, Tianjing Chen, Zhili Li*, Monitoring changes of docosahexaenoic acid-containing lipids during the recovery process of traumatic brain injury in rat using mass spectrometry imaging, Scientific Reports, 2017, 7. e5054.

(10) Yumei Guo, Junling Ren, Xiaoou Li, Xiaofeng Liu, Ning Liu, Yanmin Wang, Zhili Li*, Simultaneous Quantification of Serum Multi-Phospholipids as Potential Biomarkers for Differentiating Different Pathophysiological states of lung, stomach, intestine, and pancreas, Journal of Cancer, 2017, 8(12), 2191-2204.

(11) Dan Zhou, Shuai Guo, Mo Zhang, Yujie Liu, Tianjing Chen, Zhili Li*, Mass spectrometry imaging of small molecules in biological tissues using graphene oxide as a matrix, Analytica Chimica Acta, 2017, 962, 52-59.

(12) Junling Ren, Dan Zhang, Yujie Liu, Ruiqing Zhang, Huiling Fang, Shuai Guo, Dan Zhou, Mo Zhang, Yupin Xu, Ling Qiu*, Zhili Li*, Simultaneous Quantification of Serum Nonesterified and Esterified Fatty Acids as Potential Biomarkers to Differentiate Benign Lung Diseases from Lung Cancer, Scientific Reports, 2016, 6, e34201.

(13) Dan Zhang, Bingchao Chen, Yanmin Wang, Peng Xia, Chengyan He, Yujie Liu, Ruiqing Zhang, Mo Zhang, Zhili Li* Disease-specific IgG Fc N-glycosylation as personalized biomarkers to differentiate gastric cancer from benign gastric diseases, Scientific Reports, 2016, 6, e25957.

(14) Manwen He, Shuai Guo, Junling Ren, Zhili Li*, In Situ Characterizing Membrane Lipid Phenotype of Human Lung Cancer Cell Lines Using Mass Spectrometry Profiling, Journal of Cancer, 2016, 7(7), 810-816.

(15) Yaping Zhang, Chengyan He, Ling Qiu, Yanmin Wang, Xuzhen Qin, Yujie Liu, Zhili Li*, Serum unsaturated free fatty acids: a potential biomarker panel for early-stage detection of colorectal cancer, Journal of Cancer, 2016, 7(4), 477-483.

(16) Yujie Liu, Yuanjun Liu, Dan Zhang, Ruiqing Zhang, Zhili Li*, Kapok fiber: a natural biomaterial for highly specific and efficient enrichment of sialoglycopeptides, Analytical Chemistry, 2016, 88(2),1067-1072.

(17) Yujie Liu, Dan Zhang, Yuhang Cheng*, Zhili Li*, Elevated serum immunoinflammation-related protein complexes are associated with psychosis, Psychiatry Research, 2015, 230, 96-101.

(18) Yaping Zhang, Ling Qiu, Chengyan He, Yanmin Wang, Yujie liu, Dan Zhang, Zhili Li*, Serum unsaturated free fatty acids: a potential biomarker panel for differentiating benign thyroid diseases from thyroid cancer, Journal of Cancer, 2015, 6(12), 1276-1281.

(19) Shuai Guo, Yanmin Wang, Dan Zhou, and Zhili Li*, Electric Field-Assisted Matrix Coating Method Enhances the Detection of Small Molecule Metabolites for Mass Spectrometry Imaging, Analytical Chemistry, 2015, 87(12), 5860-5865.

(20) Manwen He, Shuai Guo, Zhili Li*, In situ characterizing membrane lipid phenotype of breast cancer cells using mass spectrometry profiling, Scientific Reports, 2015, 5, e11298.

(21) Manwen He, Shuai Guo, Zhili Li*, Dynamically in situ monitoring lipid changes in DHA-treated breast cells by matrix-assisted laser desorption/ionization Fourier transform ion cyclotron resonance mass spectrometry, Rapid Commun Mass Spectrom, 2015, 29(10), 987-990.

(22) Gaoguang Song, Yujie Liu, Yanying Wang, Guanjun Ren, Shuai Guo, Junling Ren, Li Zhang*, Zhili Li*, Personalized biomarkers to monitor disease progression in advanced non-small-cell lung cancer patients treated with icotinib, Clinica Chimica Acta, 2015, 440, 44-48.

(23) Yaping Zhang, Ling Qiu, Yanmin Wang, Chengyan He, Xuzhen Qin, Yujie liu, Zhili Li*, Unsaturated free fatty acids: a potential biomarker panel for early detection of gastric cancer, Biomarkers, 2014, 19(8), 667-673.

(24) Shuai Guo, Yanmin Wang, Dan Zhou, Zhili Li*, Significantly increased monounsaturated lipids relative to polyunsaturated lipids in six types of cancer microenvironment are observed by mass spectrometry imaging, Scientific Reports, 2014, 4, e5959.

(25) Yaping Zhang, Chengyan He, Ling Qiu, Yanmin Wang, Li Zhang, Xuzhen Qin, Yujie Liu, Dan Zhang, Zhili Li*, Serum Unsaturated Free Fatty Acids: Potential Biomarkers for Early Detection and Disease Progression Monitoring of Non-Small Cell Lung Cancer, Journal of Cancer, 2014, 5(8), 706-714.

(26) Yaping Zhang, Lina Song, Ning Liu, Chengyan He*, Zhili Li*, Decreased serum levels of free fatty acids are associated with breast cancer, Clinica Chimica Acta, 2014, 437, 31-37.

(27) Shuai Guo, Ling Qiu, Yanming Wang, Xuzhen Qin, Hui Liu, Manwen He, Yaping Zhang, Zhili Li* and Xiaohong Chen*, Tissue imaging and serum lipidomic profiling for screening potential biomarkers of thyroid tumors by matrix-assisted laser desorption/ionization-Fourier transform ion cyclotron resonance mass spectrometry, Analytical and Bioanalytical Chemistry, 2014, 406, 4357-4370.

(28) Yaping Zhang, Ling Qiu, Yanmin Wang, Xuzhen Qin, Zhili Li*, High-throughput and high-sensitivity quantitative analysis of serum unsaturated fatty acids by chip-based nanoelectrospray ionization-Fourier transform ion cyclotron resonance mass spectrometry: early stage diagnostic biomarkers of pancreatic cancer. Analyst, 2014, 139 (7), 1697-1706.

(29) Yanying Wang, Gaoguang Song, Yanmin Wang, Ling Qiu, Xuzhen Qin, Hui Liu, Fang Li, Xiaodong Wang, Fenjie Li, Shuai Guo, Yaping Zhang, Zhili Li*, Elevated serum levels of circulating immunoinflammation-related protein complexes are associated with cancer. Journal of Proteome Research, 2014, 13 (2), 710–719.

(30) Guoqiang Chen, Hexiang Li, Ling Qiu, Xuzhen Qin, Hui Liu, Zhili Li*, Change in fucosylated IgG2 Fc-glycoforms in pancreatitis and pancreatic adenocarcinoma: A promising disease classification model. Analytical and Bioanalytical Chemistry, 2014, 406, 267-273.

(31) Yaping Zhang, Yanmin Wang, Shuai Guo, Yumei Guo, Hui Liu, Zhili Li*, Ammonia-treated N-(1-naphthyl) ethylenediamine dihydrochloride as a novel matrix for rapid quantitative and qualitative determination of serum free fatty acids by matrix-assisted laser desorption/ionization-Fourier transform ion cyclotron resonance mass spectrometry, Analytica Chimica Acta, 2013, 974, 82-89.

(32) Fenjie Li, Xiaodong Wang, Yujie Liu, Hui Liu, Zhili Li* Dephosphorylation of Intact Glycoprotein to Greatly Improve Digestion Efficiency Coupled with Matrix-Assisted Laser Desorption/Ionization- Fourier Transform Ion Cyclotron Resonance Mass Spectrometric Analysis. Analytica Chimica Acta, 2013, 787, 140-147.

(33) Guoqiang Chen, Yanmin Wang, Xuzhen Qin, Hexiang Li, Yumei Guo, Yanying Wang, Hui Liu, Xiaodong Wang, Gaoguang Song, Fang Li, Fenjie Li, Shuai Guo, Ling Qiu, Zhili Li* Change in IgG1 Fc N-linked glycosylation in human lung cancer: Age and sex-related diagnostic potential. Electrophoresis 2013, 34 (16),2407-2416.DOI: 10.1002/elps.201200455.

(34) Guoqiang Chen, Li Zhang, Yanying Wang, Yumei Guo, Hui Liu, Zhili Li*. Probing gender-specific change in IgG1 Fc-galactosylation in non-small cell lung cancer patients treated with epidermal growth factor receptor inhibitor, icotinib hydrochloride, using matrix-assisted laser desorption/ionization Fourier transform ion cyclotron resonance mass spectrometry, Rapid Commun Mass Spectrom 2013, 27(10), 1168-1172.

(35) Fang Li, Xuzhen Qin, Haiquan Chen, Ling Qiu, Yumei Guo, Hui Liu, Guoqiang Chen Gaoguang Song, Xiaodong Wang, Fenjie Li, Shuai Guo, Baohua Wang and Zhili Li*, Lipid profiling for early diagnosis and progression of colorectal cancer using direct-infusion electrospray ionization Fourier transform ion cyclotron resonance mass spectrometry, Rapid Communications in Mass Spectrometry, 2013, 27(1), 24-34.

(36) Yumei Guo, Xianmin Wang, Ling Qiu, Xuzhen Qin, Hui Liu, Yanying Wang, Fang Li, Xiaodong Wang, Guoqiang Chen, Gaoguang Song, Fenjie Li, Shuai Guo, Zhili Li*, Probing gender-specific lipid metabolites and diagnostic biomarkers for lung cancer using Fourier transform ion cyclotron resonance mass spectrometry, Clinica Chimica Acta, 2012, 414, 135-141.

(37) Xiaodong Wang, Fenjie Li, Gaoguang Song, Shuai Guo, Hui Liu, Guoqiang Chen, Zhili Li*, Broad-spectrum four-dimensional orthogonal electrophoresis: a novel comprehensively feasible system for protein complexomics investigation, Molecular & Cellular proteomics, 2012, 11(9), 786-799.

(38) Guoqiang Chen, Yanmin Wang, Ling Qiu, Xuzhen Qin, Hui Liu, Xiaodong Wang, Yanying Wang, Gaoguang Song, Fang Li, Yumei Guo, Fenjie Li, Shuai Guo, Zhili Li*, Human IgG Fc-glycosylation profiling reveals association with age, sex, female sex hormones and thyroid cancers, Journal of Proteomics, 2012, 75(10), 2824-2834.

(39) Xiaodong Wang, Guoqiang Chen, Hui Liu, Zhiyun Zhao, Zhili Li*，Four-dimensional orthogonal electrophoresis system for screening protein complexes and protein-protein interactions combined with mass spectrometry, Journal of Proteome Research, 2010, 9(10), 5325-5334.

(40) Guoqiang Chen, Hui Liu, Xiaodong Wang, Zhili Li*, In vitro methylation by methanol: Proteomic screening and prevalence investigation, Analytica Chimica Acta, 2010, 661(1), 67-75.

(41) Zhiili Li, Feng Song, Zhihao Zhuang, Debra Dunaway-Mariano and Karen S. Anderson*, Monitoring Enzyme Catalysis in the Multimeric State: Direct Observation of Arthrobacter 4-Hydroxybenzoyl-Coenzyme A Thioesterase Catalytic Complexes using Time-resolved Electrospray Ionization Mass Spectrometry. Analytical Biochemistry, 2009, 394, 209-216.

(42) Zhili Li, Apurba K. Sau, Cristina M. Furdui and Karen S. Anderson*, Probing the role of tightly bound phosphoenolpyruvate in Escherichia coli 3-deoxy-d-manno-octulosonate 8-phosphate synthase catalysis using quantitative time-resolved electrospray ionization mass spectrometry in the millisecond time range, Analytical Biochemistry, 2005, 343(1), 35-47.

(43) Zhili Li, Apurba Sau, Shida Shen, Craig Whitehouse, Timor Baasov and Karen S. Anderson* , A snapshot of enzyme catalysis using electrospray ionization mass spectrometry, Journal of the American Chemical Society，2003,125, 9938-9939.

6. 課題組近5年專(zhuān)利

(1)一種基于氧化銅/氮化碳無(wú)酶葡萄糖傳感器的制備方法及應用, 申請號：201910433447

(2)一種基于氧化銅/氮化碳無(wú)酶葡萄糖傳感器的制備方法及應用，申請號：201910269990.1

(3)確定或輔助監測癌癥進(jìn)展的個(gè)體化標志物，專(zhuān)利號：ZL201610369521.3.

(4)一種富集分離唾液酸化糖肽的新材料及其應用, 專(zhuān)利號：ZL201610506699.8

(5)一組監測癌癥疾病進(jìn)展和或耐藥性產(chǎn)生的個(gè)體化標志物,申請號：201510827734.1

(6)一種富集唾液酸化糖肽的材料及其應用，申請號：ZL201510651116.6

(7)一種原位質(zhì)譜分析的常壓離子源裝置，專(zhuān)利號：ZL201520119228.2

(8)一種用于質(zhì)譜成像的基質(zhì)噴涂裝置，專(zhuān)利號：ZL201420766737.x

(9)一種富集唾液酸化糖肽、唾液酸化聚糖或唾液酸化糖苷的方法, 申請號：ZL201410035250.9

(10)蛋白質(zhì)復合物及其譜以及其在疾病診斷、進(jìn)展評估和藥效評估中的應用， 申請號：PCT/CN2012/071113

二、 許雪梅課題組

1. 課題組簡(jiǎn)介

疫苗是因傳染性疾病的預防所需而問(wèn)世的，包括傳統的急性傳染病以及慢性傳染病（如HBV及HPV等感染相關(guān)疾病），在對抗傳染病的中起著(zhù)十分重要的作用。但目前上市疫苗還存在一些缺陷，主要是保護范圍不夠理想，如HPV黏膜致癌型約20多型、黏膜低危型約12型，但目前上市的4種HPV病毒樣顆粒（VLP）蛋白多價(jià)疫苗中，最高的9價(jià)苗僅能保護7種致癌型、2種低危型；腸道病毒EV71手足口病滅活苗17年在我國問(wèn)世應用后，手足口病的發(fā)病率并沒(méi)有下降，目前尚無(wú)多價(jià)手足口病疫苗的問(wèn)世；四價(jià)流感病毒的保護效率也難以滿(mǎn)足流感預防的要求，且會(huì )出現預測病毒株與現實(shí)流行株不一致，導致疫苗脫靶。本課題組的主要研究方向，首先是采用基因工程重組蛋白技術(shù)，研制通用型HPV嵌合病毒樣顆粒(cVLP)疫苗、多價(jià)手足口病病毒樣顆粒疫苗及通用型流感病毒疫苗。目前HPV通用疫苗的專(zhuān)利技術(shù)已經(jīng)轉讓?zhuān)摷夹g(shù)為表面展示保守表位的HPV cVLP疫苗，動(dòng)物實(shí)驗結果表明多種cVLP聯(lián)合應用具有協(xié)同加強作用，中和不僅沒(méi)有交叉抑制現象，同時(shí)還可協(xié)同強化針對部分交叉和型別的中和抗體滴度，具有廣譜的交叉中和活性，可至少中和24余種HPV型別，包括所有12種高危型、大部分少見(jiàn)的致癌型，同時(shí)還2種主要低危型和4種皮膚型；手足口病多價(jià)疫苗及流感病毒通用型疫苗正在進(jìn)行中。其次是開(kāi)展各種疫苗佐劑的研究，包括傳統的鋁佐劑、具有TLR刺激活性的新型小分子化合物佐劑、乳劑及新型復合佐劑等的研究。HPV治療性疫苗，主要選擇與病毒感染及感染相關(guān)惡性表型維持必需的癌蛋白為靶抗原，定點(diǎn)突變后消除其轉化活性，進(jìn)行融合各種免疫刺激分子的基因疫苗研究。

2. 課題組負責人介紹

許雪梅，女，1965年出生，博士，研究員，博士生導師，中國醫學(xué)科學(xué)院基礎醫學(xué)研究所 腫瘤病毒疫苗課題組組長(cháng)。

教育經(jīng)歷：
1983.9-1988.7：山東醫科大學(xué) 醫學(xué)學(xué)士學(xué)位；
1988.8-1991.7：大連醫科大學(xué) 病理學(xué)碩士學(xué)位；
1999.8-2002.7：中國協(xié)和醫科大學(xué)基礎醫學(xué)院 博士學(xué)位；
2002.12-2004.9：美國芝加哥Loyola大學(xué)癌癥研究中心，訪(fǎng)問(wèn)學(xué)者。
工作經(jīng)歷：
1991.8-1995.7：山東青島第五人民醫院 病理科 主治醫師；
1995.7-2002.12：中國醫學(xué)科學(xué)院基礎醫學(xué)研究所 助理研究員、副研究員；
2004.9-至今：中國醫學(xué)科學(xué)院基礎醫學(xué)研究所研究員、病原生物學(xué)專(zhuān)業(yè)博士生導師，腫瘤病毒課題組組長(cháng)。

3. 課題組成員介紹

張婷，助理研究員，博士，郵箱：zt_0315@163.com，電話(huà)：010-69156442

王志榮，助理研究員，博士，郵箱：zhrwang2012@126.com，電話(huà)：010-69156442

4. 課題組主要科研項目

5. 課題組近5年代表性論文

(1) Ting Zhang, Xue Chen, Guoyang Liao, Meili Hu, Jianqing Xu*, Xuemei Xu*. Induction of cross-neutralizing antibodies by sequential immunization with heterologous papillomavirus L1VLPs and its implications for HPV prophylactic vaccines. Journal of Medical Virology, 2020. Doi: ?10.1002/jmv.25690.

(2) Ting Zhang, Xue Chen, Hongyang Liu, Qifeng Bao, Zhirong Wang, Guoyang Liao*, Xuemei Xu*. ?A rationally designed flagellin-L2 fusion protein induced serum and mucosal neutralizing antibodies against multiple HPV types. Vaccine, 37(30): 4022~4030, 2019.

(3)郝亞茹，張婷，劉洪洋，王志榮，周艷，夏百成，許雪梅*. HPV31 L1 C端截短基因可在昆蟲(chóng)細胞表達體系中高水平制備HPV L1疫苗. 基礎醫學(xué)與臨床，39(3): 343-347, 2019.

(4) Xue Chen, Ting Zhang, Hongyang Liu, Yaru Hao, Guoyang Liao, Xuemei Xu*. Displaying 31RG-1 peptide on the surface of HPV16 L1 by use of a human papillomavirus chimeric virus-like particle induces cross-neutralizing antibody responses in mice. Human Vaccines & Immunotherapeutics, 14(8): 2025~2033, 2018.

(5)陳雪，王志榮，劉洪洋，張婷，許雪梅* . 一種可誘發(fā)高滴度的針對人乳頭瘤病毒HPV16，HPV52，HPV58中和抗體反應的HPV16嵌合病毒樣顆粒疫苗的研究. 病毒學(xué)報，34(4)：505-514, 2018.

(6)胡美麗，劉洪洋，王志榮，陳雪，張婷，許雪梅*.原核表達系統制備HPV58L1 VLP可誘發(fā)高滴度且持久的中和抗體. 現代生物醫學(xué)進(jìn)展, 18(3):418-422, 2018.

(7) Xue Chen, Hongyang Liu, Zhirong Wang, Shuo Wang, Ting Zhang, Meili Hu, Liang Qiao, Xuemei Xu*. Human papillomavirus 16L1-58L2 chimeric virus-like particles elicit durable neutralizing antibody responses against a broad-spectrum of human papillomavirus types. Oncotarget, 8(38): 63333~63344, 2017.

(8)張婷，陳雪，劉洪洋，周艷，王志榮，許雪梅*. HPV 31型L2保守中和表位可誘發(fā)廣譜中和抗體. 基礎醫學(xué)與臨床，31(11)：1552-1556, 2017.

(9) Ting Zhang, Hongyang Liu, Xue Chen, Zhirong Wang, Shuo Wang, Chunfeng Qu, Jingzhi Zhang, Xuemei Xu*. Lipidated L2 epitope repeats fused with a single-chain antibody fragment targeting human Fc gamma RI elicited cross-neutralizing antibodies against a broad spectrum of human papillomavirus types. Vaccine, 34(46): 5531~5539, 2016.

6. 課題組近5年專(zhuān)利

(1)      一種乳頭瘤病毒嵌合蛋白及其用途，CN201610146109.5（已授權，已轉讓?zhuān)?/span>

(2)      一種乳頭瘤病毒嵌合蛋白及其用途，PCT/CN2017/075402（已授權，已轉讓?zhuān)?/span>

(3)      截短型人乳頭瘤病毒16型L1蛋白及其應用，CN201710153290.7（已授權，已轉讓?zhuān)?/span>

(4)      截短型人乳頭瘤病毒58型L1蛋白及其應用，CN201610147709.3（已授權，已轉讓?zhuān)?/span>

(5)      一種乳頭瘤病毒嵌合蛋白及其用途，CN201610146116.5（已授權）

(6)      一種復合疫苗佐劑及其應用，CN201710152761.2

三、 王晨軒課題組

1. 課題組簡(jiǎn)介

研究方向：蛋白質(zhì)的正確折疊與組裝是維持人體生理機能的必需。肽鏈通過(guò)精密地調控分子間相互作用自組裝形成有序三維分子結構，進(jìn)一步組裝、聚集、相分離，形成執行生理功能的分子機器與無(wú)膜細胞器。蛋白質(zhì)組裝穩態(tài)失衡是一系列退行性疾病共同的病理生理基礎。研究蛋白質(zhì)組裝過(guò)程與結構，認識自組裝過(guò)程中的分子間相互作用的本質(zhì)與規律，實(shí)現對自組裝過(guò)程與功能的有效調控對蛋白質(zhì)組裝相關(guān)疾病的預防和治療有重要意義，從經(jīng)典藥物治療到相關(guān)新型藥物治療的興起，從微觀(guān)層面對發(fā)病分子機理的闡述到宏觀(guān)層面治療模式的創(chuàng )新，新的認識將在未來(lái)改變相關(guān)疾病的診治模式，為患者改善預后帶來(lái)新的機遇。王晨軒課題組遵循“認識組裝-調控組裝-利用組裝”的研究思路，發(fā)展掃描隧道顯微術(shù)、原子力探針顯微術(shù)、核磁共振波譜技術(shù)、X-射線(xiàn)單晶衍射、光散射等新穎的物理、物理化學(xué)方法用于生物大分子的結構測定，在單分子水平理解與重大疾病發(fā)生、發(fā)展密切相關(guān)的蛋白、多肽的折疊、組裝結構和過(guò)程，認識蛋白、多肽折疊組裝過(guò)程中的相互作用本質(zhì)與調控規律。

2. 課題組負責人介紹

王晨軒，男，1986年出生，博士，副研究員，碩士生導師，中國醫學(xué)科學(xué)院基礎醫學(xué)研究所課題組組長(cháng)。2004-2008年，蘭州大學(xué)國家理科化學(xué)基地班，本科。2008-2013年，中國科學(xué)院國家納米科學(xué)中心與清華大學(xué)化學(xué)系聯(lián)合培養研究生，物理化學(xué)專(zhuān)業(yè)。導師王琛研究員、楊延蓮研究員、李艷梅教授。研究方向：淀粉樣蛋白折疊結構的研究及多肽-藥物相互作用。2013年獲清華大學(xué)理學(xué)博士學(xué)位。2010年，丹麥奧胡斯大學(xué)多學(xué)科交叉納米中心-物理與天文系訪(fǎng)問(wèn)學(xué)者。合作導師丹麥皇家科學(xué)院院士、中國科學(xué)院外籍院士Flemming Besenbacher，董明東教授。研究方向：膜蛋白的超高分辨原子力探針顯微術(shù)的單分子成像。2013-2018年，美國威斯康星大學(xué)麥迪遜校區化學(xué)系，化學(xué)與生物工程系博士后。合作導師美國工程院院士Nicholas L. Abbott教授，美國科學(xué)院院士Samuel H. Gellman教授。研究方向：多肽的折疊結構與單分子力學(xué)研究。2018年至今，中國醫學(xué)科學(xué)院基礎醫學(xué)研究所/北京協(xié)和醫學(xué)院基礎學(xué)院生物物理與結構生物學(xué)系工作。

3. 課題組成員介紹

張文博，助理研究員，博士，郵箱： zwb@ibms.pumc.edu.cn，電話(huà)：010-69156463

于蘭蘭，博士后，博士，郵箱：yull@ibms.pumc.edu.cn，電話(huà)：010-6915644263

4. 課題組主要科研項目

5. 課題組近5年代表性論文

(1) Lanlan Yu*, Wenbo Zhang, Wendi Luo, Robert L. Dupont, Yang Xu, Yibing Wang, Bin Tu, Haiyan Xu, Xiaoguang Wang, Qiaojun Fang#, Yanlian Yang, Chen Wang, Chenxuan Wang#. Molecular recognition of human islet amyloid polypeptide assembly by selective oligomerization of thioflavin T, Science Advances, 2020, 6, eabc1449.

(2) Wenbo Zhang*, Lanlan Yu, Chenxuan Wang#. Intermolecular interactions and self-assembly of peptide-based nanomaterials against human pathogenic bacteria. In: Haiyan Xu, Ning Gu. (eds) Nanotechnology in regenerative medicine and drug delivery therapy. 2020, Springer, Singapore.

(3) Wenbo Zhang*, Lanlan Yu, Tianjiao Ji#, Chenxuan Wang#, Tumor microenvironment-responsive peptide based supramolecular drug delivery system, Frontiers in Chemistry, 2020, 8, 549.

(4) Qize Xuan*, Jiaxin He, Min Li, Ruoshi Chai, Chenxuan Wang#, Yibing Wang#, Ping Wang, Monomer-targeting affinity peptide inhibitors of amyloid with no self-fibrillation and low cytotoxicity, Chemical Communications, 2020, 56, 1633-1636.

(5) Xiaoyun Li*, Zhu Liang*, Jianchao Du*, Zhiqing Wang, Song Mei, Zhiqing Li, Yan Zhao, Dandan Zhao, Yiming Ma, Jun Ye, Jiantao Xu, Yu Zhao, Jiahui Chang, Yuhao Qin, Lanlan Yu, Chenxuan Wang#, Chengyu Jiang#, Herbal decoctosome is a novel form of medicine, Science China-Life Sciences, 2019, 62, 333–348.

6. 課題組近5年專(zhuān)利

(1) 王晨軒，鄧準，于蘭蘭，張文博，祖瑞涓，鄭明睿. 一種低溶血活性的蜂毒肽及其應用。國家發(fā)明專(zhuān)利.專(zhuān)利號 ZL201910854177.0

(2) 王晨軒，鄧準，于蘭蘭，張文博，祖瑞涓，鄭明睿. 一種蜂毒肽變體及其應用。國家發(fā)明專(zhuān)利.專(zhuān)利號 ZL201910854956.0