Research Areas

The Lei Zhang lab focuses on utilizing single-cell omics to unravel the pathogenesis and mechanisms of immunotherapies in cancer and other immune-related diseases, aiming to rationalize the selection of current treatment strategies. More specifically, we use combined single-cell analyses from mouse models and patients to delineate the function of treatment-related immune cell subsets, dissect novel mechanisms of immunotherapies, and explore how pre-cancer turns into cancer. Prof. Lei Zhang has systematically depicted the fundamental properties of single immune cells in colorectal cancer and identified specific lymphoid and myeloid subsets related to immunotherapies. She has also co-developed a novel analysis framework to track the dynamic relationships of T cells in human tissues.

Highlights

During her Ph.D. period, Dr. Zhang Lei was mainly engaged in the research and application of non-coding RNA in tumorigenesis and development, including studying the activity and specificity of siRNA and miRNA through in vitro screening platform, such as targeting breast cancer estrogen receptor miRNA function, And explore non-coding RNA as a marker for early diagnosis and prognosis of breast cancer. During her Ph.D., she published two first-author articles and participated in obtaining a Chinese authorized patent. During her postdoctoral period, Dr. Zhang Lei was mainly engaged in a series of studies on the analysis of colorectal cancer tumor microenvironment, immunotherapy response and resistance mechanism with single-cell omics technology. So far, Dr. Zhang Lei has published more than 10 papers in top professional journals such as "Nature", "Cell", "Nature Medicine", "Cancer Immunology Research", "Cell Research", "Genome Biology", including " 5 first or co-first author articles such as Nature" and "Cell".

Dr. Zhang Lei’s main scientific contributions in the field of single cell omics and tumor immunity include (1) the first systematic analysis of the transcriptome and T cell receptor (TCR) of colorectal cancer infiltrating T cells at the single cell level Repertoire characteristics; (2) For the first time, analyze the differences in T cell subtypes of colorectal cancer patients with unstable and stable genomic microsatellites from the single-cell level, and find the potential impact on the differences in the response of colorectal cancer patients to PD-1 blockers A new type of helper T cell subset (BHLHE40+ Th1-like T cells) (this major discovery has been widely recognized and cited by journals such as Nature, Cell, Nature Medicine and Nature Reviews); (3) Co-developed integration The STARTRAC bioinformatics method of single-cell transcriptome and TCR comprehensively characterizes the dynamic relationship between patients' T cells (this method has achieved the top ten progress in China's bioinformatics in 2018); (4) The first time for the colorectal from the single-cell level Interpretation of the subtypes of cancer-infiltrating myeloid immune cells and their interaction network; (5) Revealing the new mechanisms of two targeted myeloid immune cell therapies (anti-CSF1R and anti-CD40) for colorectal cancer at the single-cell scale for the first time , A class of immune cells and molecules (SPP1 + TAM) discovered that affect the drug resistance of targeted tumor-associated macrophage blockers can be used as new strategies and next-generation targets for the development of colorectal cancer immunotherapy drugs; (6) The first to integrate single-cell omics data for the treatment of tumor patients and mouse tumor models, to study tumor immunotherapy mechanisms and examples of applications (the results were selected as one of the 9 best medical studies in the world in 2020 by the "Cell" magazine) .

Honors

• 2020 – 2021    High-Level Professional in Shenzhen (National-Level Talent)

• 2018 – 2019    Bayer-Peking University Center for Translational Research Postdoc 

• 2018 – 2019    Outstanding Postdoctoral Research Fellow, PKU 

• 2016 – 2019    Outstanding Postdoctoral Fellowship, Center for Life Sciences, Peking University, CLS 

• 2012 – 2013    May 4th Scholarship, PKU 

• 2011 – 2012    Guanghua Scholarship, PKU 

Related News

Interview：

CLS | https://mp.weixin.qq.com/s/5CLquUjsR1NYCedtwS6z2g

Works on  T Cells of Colorectal Cancer（Nature）:

Chinese Society for Immunology, CSI | http://www.csi.org.cn/article/content/view?id=804

ScienceNet.cn | http://news.sciencenet.cn/htmlnews/2018/10/419287.shtm

BioArt | https://mp.weixin.qq.com/s/ycc5kvshNrTYEkKt-Lldtg

GeneClub | https://mp.weixin.qq.com/s/GZmB171JL_rvdaIP88lpLw

SeqChina | https://mp.weixin.qq.com/s/BYOCpZaQY9tCtFAOVwcp1A

PKU | https://news.pku.edu.cn/xwzh/2018-10/29/content_304811.htm

BIOPIC | http://biopic.pku.edu.cn/zxdt/270092.htm

PKU | http://web.bio.pku.edu.cn/index.php?s=/Index/news_cont/id/14188.html

CLS | http://www.cls.edu.cn/Research/Research_Achievements4342.shtml

Works on Myeloid Cell of Colorectal Cancer（Cell）:

Cell (Best of 2020) | https://info.cell.com/best-of-cell-2020 

MedSci | https://mp.weixin.qq.com/s/6yVJDXsYQojlDYrvux7oOg

丁香学术 | https://mp.weixin.qq.com/s/wW5L5HISNpyUTNVxH7hehg

ScienceNet.cn | http://news.sciencenet.cn/htmlnews/2020/4/438588.shtm

CellPress | https://mp.weixin.qq.com/s/WUySrADnJJyakAYGDf3d3w

BioArt | https://mp.weixin.qq.com/s/eEG8RHl3T1VFctYLrmfk1A

PKU | https://news.pku.edu.cn/jxky/8ef323c49dbf4ab1ae4aa9843555e379.htm

BIOPIC | https://mp.weixin.qq.com/s/Nn6TjmTVRlbNDnXrRJ3ZMg

PKU | http://www.bio.pku.edu.cn/homes/Index/news_cont/22/14963.html

PKU | http://www.aais.pku.edu.cn/yanjiu/shownews.php?id=1001

CLS | http://www.cls.edu.cn/Research/Research_Achievements4903.shtml

Sohu | https://www.sohu.com/a/388666069_722566

Tencent | https://new.qq.com/omn/20200417/20200417A085G700.html

Selected Publications

1. Lei Zhang#; Xin Yu#; Liangtao Zheng#; Yuanyuan Zhang#; Yansen Li; Qiao Fang; Ranran Gao; Boxi Kang; Qiming Zhang; Julie Y. Huang; Hiroyasu Konno; Xinyi Guo; Yingjiang Ye; Songyuan Gao; Shan Wang; Xueda Hu; Xianwen Ren; Zhanlong Shen*; Wenjun Ouyang*; Zemin Zhang*; Lineage tracking reveals dynamic relationships of T cells in colorectal cancer. Nature, 2018, 564(7735): 268-272.  

2. Lei Zhang; Zemin Zhang*; Recharacterizing tumor-infiltrating lymphocytes by single-cell RNA sequencing. Cancer Immunology Research, 2019, 7(7): 1040-1046.    

3. Lei Zhang#; Ziyi Li#; Katarzyna M. Skrzypczynska#; Qiao Fang; Wei Zhang; Sarah A. O'Brien; Yao He; Lynn Wang; Qiming Zhang; Aeryon Kim; Ranran Gao; Jessica Orf; Tao Wang; Deepali Sawant; Jiajinlong Kang; Dev Bhatt; Daniel Lu; Chi-Ming Li; Aaron S. Rapaport; Kristy Perez; Yingjiang Ye; Shan Wang; Xueda Hu; Xianwen Ren; Wenjun Ouyang; Zhanlong Shen*; Jackson G. Egen*; Zemin Zhang*; Xin Yu*; Single-cell analyses inform mechanisms of myeloid-targeted therapies in colon cancer. Cell, 2020, 181(2): 442-459.    

4. Xianwen Ren#; Lei Zhang#; Yuanyuan Zhang; Ziyi Li; Nathan Siemers; Zemin Zhang*; Insights gained from single-cell analysis of immune cells in the tumor microenvironment. Annual Review of Immunology, 2021, 39: 583-609.

5. Hu Nie; Peilu Lin; Yu Zhang; Yihong Wan; Jiesheng Li; Chengqian Yin; Lei Zhang*; Single-cell meta-analysis of inflammatory bowel disease with scIBD. Nature Computational Science, 2023, 3: 522–531.