Dr. Wei Wei is an Assistant Professor at the Institute for Systems Biology. He also has the positions of Affiliated Assistant Professor at the UCLA Department of Molecular and Medical Pharmacology and member of the Jonsson Comprehensive Cancer Center. He received his B.S. in Fundamental Sciences (Mathematics and Physics) at Tsinghua University (Beijing) and M.S. in Materials Sciences and Engineering at UC San Diego. He obtained his Ph.D. at California Institute of Technology in 2014 with cross-disciplinary training that included both physical and biological sciences. Before joining ISB, Wei was an Assistant Professor at UCLA until mid-2018.
Wei received the Chinese Government Award for Outstanding Student Abroad in 2013. In 2014, he was the sole recipient of the Milton and Francis Clauser Doctoral Prize – the highest honor for a Caltech Ph.D. He received the Andy Hill Cancer Research Endowment Distinguished Researchers award in 2019. Currently, he is the co-director of the NCI-funded ISB/UCLA Physical Sciences in Oncology Program (PS-OP), and a Project Lead in NCI-funded NSB Cancer Center.
Wei’s research interests reside in a highly cross-disciplinary field of BioMEMS, molecular and cellular analysis, and systems biomedicine. Wei’s group is developing and deploying a unique suite of single-cell tools and computational approaches to cultivate new understanding in cancer systems biology and address significant questions in translational cancer research.
Single-cell analysis, BioMEMS, cancer molecular diagnosis, cancer epigenetic plasticity, multivariate data analysis
2014 Ph.D. in Materials Sciences, California Institute of Technology
2008 M.S. in Materials Sciences and Engineering, UC San Diego
2005 B.S. in Fundamental Sciences (Mathematics and Physics), Tsinghua University
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Flower, Cameron T., Chunmei Liu, James R. Heath, Wei Wei, and Forest M. White. 2023. “Abstract 4876: A Systems Pharmacology Approach to Discover Synergistic Targeted Therapy Combinations.”
Cancer Research 83 (7_Supplement): 4876.
https://doi.org/10.1158/1538-7445.AM2023-4876.
Cite
Ye, Shengda, Bin Yang, Tingbao Zhang, Wei Wei, Zhiqiang Li, Jincao Chen, and Xiang Li. 2022. “Identification of an Immune-Related Prognostic Signature for Glioblastoma by Comprehensive Bioinformatics and Experimental Analyses.”
Cells 11 (19): 3000.
https://doi.org/10.3390/cells11193000.
Cite
Su, Yapeng, Dan Yuan, Daniel G. Chen, Rachel H. Ng, Kai Wang, Jongchan Choi, Sarah Li, et al. 2022. “Multiple Early Factors Anticipate Post-Acute COVID-19 Sequelae.”
Cell 0 (0).
https://doi.org/10.1016/j.cell.2022.01.014.
Cite
Guo, Zhili, Hanjun Cheng, Zhonghan Li, Shiqun Shao, Priyanka Sarkar, Siwen Wang, Rohit Chaudhuri, et al. 2021. “Single-Cell Profiling of Fatty Acid Uptake Using Surface-Immobilized Dendrimers.”
Journal of the American Chemical Society 143 (29): 11191–98.
https://doi.org/10.1021/jacs.1c05103.
Cite
Cheng, Hanjun, Zhonghan Li, Zhili Guo, Shiqun Shao, Li Mo, Wei Wei, and Min Xue. 2021. “Single-Cell Profiling of D-2-Hydroxyglutarate Using Surface-Immobilized Resazurin Analogs.”
Biosensors & Bioelectronics 190: 113368.
https://doi.org/10.1016/j.bios.2021.113368.
Cite
Su, Yapeng, Dan Yuan, Daniel G. Chen, Kai Wang, Jongchan Choi, Chengzhen L. Dai, Sunga Hong, et al. 2021. “Heterogeneous Immunological Recovery Trajectories Revealed in Post-Acute COVID-19.”
MedRxiv, 2021.03.19.21254004.
https://doi.org/10.1101/2021.03.19.21254004.
Cite
Yang, Liu, Xiaowei Yan, Jie Chen, Qiong Zhan, Yingqi Hua, Shili Xu, Ziming Li, et al. 2021. “Hexokinase 2 Discerns a Novel Circulating Tumor Cell Population Associated with Poor Prognosis in Lung Cancer Patients.”
Proceedings of the National Academy of Sciences of the United States of America 118 (11).
https://doi.org/10.1073/pnas.2012228118.
Cite
Su, Yapeng, Guideng Li, Melissa Ko, Hanjun Cheng, Ronghui Zhu, Min Xue, Lidia Robert, et al. 2020. “Abstract 6585: Systems Biology for Investigating Drug Resistance Mechanism of Melanoma.”
Cancer Research 80 (16 Supplement): 6585–6585.
https://doi.org/10.1158/1538-7445.AM2020-6585.
Cite
Wang, Zhuo, Jie Chen, Liu Yang, Mingzhe Cao, Yanlan Yu, Rulin Zhang, Heng Quan, et al. 2020. “Single-Cell Sequencing-Enabled Hexokinase 2 Assay for Noninvasive Bladder Cancer Diagnosis and Screening by Detecting Rare Malignant Cells in Urine.”
Analytical Chemistry 92 (24): 16284–92.
https://doi.org/10.1021/acs.analchem.0c04282.
Cite
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