血清/血漿成分分析方法及其應用：

      ?  腫瘤個(gè)體化診斷及預后標志物篩選；
      ?  生物大分子復合物分析方法研究及其應用；
      ?  糖蛋白糖鏈結構分析方法研究及其應用;
      ?  代謝物分析方法研究及其應用.

質(zhì)譜成像及其應用：     
      ?  原位研究代謝物、蛋白質(zhì)變化與疾病發(fā)生之間的關(guān)系；
      ?  原位研究單細胞代謝物、蛋白質(zhì)變化與細胞表型之間的關(guān)系。

主要技術(shù)手段：質(zhì)譜技術(shù)(9.4T FTICR MS和LTQ等）、新型色譜分離技術(shù)、凝膠分離技術(shù)等。

科研合作及技術(shù)服務(wù)：為了充分利用本課題組已建立的技術(shù)平臺和方法，課題組在蛋白質(zhì)鑒定、完整蛋白質(zhì)分子量測定、二硫鍵分析、N-和C-端測序、糖基化修飾和代謝物鑒定等方面提供技術(shù)服務(wù)或合作研究。 

招募自愿者：經(jīng)過(guò)多年對血液成分變化與慢性疾病發(fā)生或腫瘤預后之間關(guān)系的研究，本課題組發(fā)現一組與慢性疾病發(fā)生和惡性腫瘤復發(fā)相關(guān)的新型個(gè)體化標志物 (國際專(zhuān)利申請號: PCT/CN2012/071113和國家專(zhuān)利號：ZL201110037632.1)。經(jīng)中國醫學(xué)科學(xué)院基礎醫學(xué)研究所倫理委員會(huì )批準(項目編號：004-2013)，本課題組長(cháng)期開(kāi)展大人群的“血液成分變化與健康狀態(tài)關(guān)系研究”。 

入選標準：年齡20-70歲，健康人群或患有單一慢性疾病患者或腫瘤患者。 

參加者：健康人群每年提供一次血液(3-4毫升)；惡性腫瘤患者或其它慢性疾病患者將依據病情適當增加檢測次數。我們將提供給參加者血液中上述標志物含量的信息。詳細內容請利用下面的聯(lián)系方式了解。 

本課題組提供博士后和課題組項目聘用人員崗位，有意者請電話(huà)或郵件聯(lián)系。

聯(lián)系方式： 
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 
生物物理學(xué)及結構生物學(xué)系 
北京市東城區東單三條五號，100005
電話(huà)：010-69156479
E-mail：lizhili@ibms.pumc.edu.cn; zhililily@aliyun.com

近5年發(fā)表的研究論文：

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, DOI:10.1002/prca.201900016

3.    Na Li, Yuming Qiu, Yunpeng Wu, Mo Zhang, Zhizhen Lai, Qing Wang, Yuying Du, Lei Guo, Shuai Liu, Zhili Li*, Association of serum total fatty acids with type 2 diabetes, Clinica Chimica Acta, 2020, 500, 59-68.

4.    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.

5.    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.

6.    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.

7.    Shuai Guo, Yanmin Wang, Dan Zhou, Yupin Xu, Tianjing Chen, Zhili Li*, Association of alteration of nucleosides and nucleotides with gastric cancer microenvironment, International Journal of Mass Spectrometry, 2018, 434, 37–42.

8.    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.

9.    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.

10.  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.

11.  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.

12.  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.

13.  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.

14.  Xiaodong Wang, Yujie Liu, Fenjie Li, Zhili Li*, Poplar catkin: a natural biomaterial for highly specific and efficient enrichment of sialoglycopeptides, Chinese Chemical Letter, 2017, 28,1018-1026.

15.  Chenchen Xu, Dan Zhou, Yixin Luo, Shuai Guo, Tao Wang, Jie Liu*, Yuehua Liu*, Zhili Li*, Tissue and serum lipidome shows altered lipid composition with diagnostic potential in mycosis fungoides, Oncotarget, 2017, 8,48041-48050.

16.  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.

17.  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, DOI: 10.1038/srep25957.

18.  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.

19.  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.

20.  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.

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

22.  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.

23.  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.

24.  Manwen He, Shuai Guo, Zhili Li*, In situ characterizing membrane lipid phenotype of breast cancer cells using mass spectrometry profiling, Scientific Reports, 2015, 5, 11298.

25.  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.

26.  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.

27.  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.

28.  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, 5959.

29.  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.

30.  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.

31.  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.

32.  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.

33.  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.

34.  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.

35.  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.

36.  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. .

37.  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.

38.  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.

39.  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.

40.  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.

41.  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.

42.  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.

授權或已申請專(zhuān)利：

1.   一組監測癌癥疾病進(jìn)展和或耐藥性產(chǎn)生的免疫球蛋白G糖基化修飾標志物，申請號：201710655611.3

2.   確定或輔助監測癌癥進(jìn)展的個(gè)體化標志物，專(zhuān)利號：201610369521.3.

3.   一種富集分離唾液酸化糖肽的新材料及其應用, 申請號：201610506699.8

4.   基于脂質(zhì)代謝譜的個(gè)體化腫瘤進(jìn)展監測標志物及其應用, 申請號：201510827734.1

5.   一種富集唾液酸化糖肽的材料及其應用，申請號：201510651116.6

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

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

8.   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, 專(zhuān)利號：201410035250.9 。

9.   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

10. 蛋白質(zhì)復合物及其在腫瘤診斷和/或預后評估中的應用，專(zhuān)利號：ZL201110037632.1。

11. 一種多發(fā)性骨髓瘤特異性蛋白及其專(zhuān)用檢測試劑盒，專(zhuān)利號：ZL201010238794.7。

12. 一種糖肽富集分離材料及其應用，申請號：ZL2010101195689.x。

13. 一種蛋白質(zhì)復合物或復合體的三維凝膠電泳分離方法，申請號：200910076496.x。