Wei Wei, PhD

Andy Hill CARE Distinguished Researcher and Associate Professor

ISB

wei.wei@isbscience.org Visit Wei Lab Website ↗

Dr. Wei Wei is an Associate Professor at the Institute for Systems Biology. He also has the position of Affiliate Faculty at the Molecular Engineering & Sciences Institute of the University of Washington. 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. Dr. Wei has been serving as either program director or project lead in various nationwide cancer research consortium-funded projects. Some of these initiatives include the NCI-funded ISB/UCLA Physical Sciences in Oncology Network Program (PS-ON), ISB/UW Innovative Molecular Analysis Technologies (IMAT) program, ISB/UCLA Centers of Cancer Nanotechnology Excellence (CCNE) program, and ISB/Yale/UCLA Cancer Systems Biology Consortium (CSBC) program.

Wei’s research interests reside in a highly cross-disciplinary field of BioMEMS, molecular and cellular analysis, and systems biomedicine. The overarching goal of the Wei Lab is to harness systems biology thinking and approaches to address critical questions and cultivate new understanding in both fundamental and translational cancer research. In cancer biology, the primary focus lies in understanding the phenotypic plasticity of cancer cells and its role in fostering non-genetic (adaptive) drug resistance, a form of resistance distinct from the Darwinian selection of resistant genotypes. The goal is to elucidate how cancer cells coordinate their internal molecular machinery to adapt to therapeutic stress and to understand how these adaptive changes evolve within the heterogeneous tumor and are modulated by the tumor microenvironment (TME). The lab scrutinizes this process across multiple molecular landscapes and at various temporal resolutions, to gain comprehensive insights at both mechanistic and systems levels. This line of inquiry also propels the development of innovative single-cell multi-omics and spatial multi-omics tools. On the translational research front, the lab is committed to advancing liquid biopsy-based predictive cancer diagnostics through the lens of disseminated/circulating tumor cells (DTCs/CTCs), and to revolutionizing functional precision medicine with needle biopsy-based organotypic drug sensitivity assays as companion diagnostics.

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

Single-cell/spatial multi-omics, cancer epigenetic plasticity, non-genetic drug resistance, functional precision medicine, cancer molecular diagnostics

2323737 2RQKSFR5 Wei Wei 1 chicago-author-date-16th-edition 50 date desc year 1 7392 https://isbscience.org/wp-content/plugins/zotpress/

%7B%22status%22%3A%22success%22%2C%22updateneeded%22%3Afalse%2C%22instance%22%3Afalse%2C%22meta%22%3A%7B%22request_last%22%3A250%2C%22request_next%22%3A50%2C%22used_cache%22%3Atrue%7D%2C%22data%22%3A%5B%7B%22key%22%3A%22D49PS9IT%22%2C%22library%22%3A%7B%22id%22%3A2323737%7D%2C%22meta%22%3A%7B%22creatorSummary%22%3A%22Su%20et%20al.%22%2C%22parsedDate%22%3A%222026%22%2C%22numChildren%22%3A1%7D%2C%22bib%22%3A%22%26lt%3Bdiv%20class%3D%26quot%3Bcsl-bib-body%26quot%3B%20style%3D%26quot%3Bline-height%3A%201.35%3B%20padding-left%3A%201em%3B%20text-indent%3A-1em%3B%26quot%3B%26gt%3B%5Cn%20%20%26lt%3Bdiv%20class%3D%26quot%3Bcsl-entry%26quot%3B%26gt%3BSu%2C%20Yapeng%2C%20Chunmei%20Liu%2C%20Xiang%20Lu%2C%20Hui-Yu%20Chuang%2C%20Guideng%20Li%2C%20Shiqun%20Shao%2C%20Yan%20Kong%2C%20et%20al.%202026.%20%26%23x201C%3BSequential%20Transcriptional%20Waves%20and%20NF-%26%23x3BA%3BB-Driven%20Chromatin%20Remodeling%20Direct%20Drug-Induced%20Dedifferentiation%20in%20Cancer.%26%23x201D%3B%20%26lt%3Bi%26gt%3BNature%20Communications%26lt%3B%5C%2Fi%26gt%3B%2017%20%281%29.%20Nature%20Publishing%20Group%3A%203228.%20%26lt%3Ba%20class%3D%26%23039%3Bzp-DOIURL%26%23039%3B%20href%3D%26%23039%3Bhttp%3A%5C%2F%5C%2Fdoi.org%5C%2F10.1038%5C%2Fs41467-026-71349-4%26%23039%3B%26gt%3Bhttp%3A%5C%2F%5C%2Fdoi.org%5C%2F10.1038%5C%2Fs41467-026-71349-4%26lt%3B%5C%2Fa%26gt%3B.%20%26lt%3Ba%20title%3D%26%23039%3BCite%20in%20RIS%20Format%26%23039%3B%20class%3D%26%23039%3Bzp-CiteRIS%26%23039%3B%20data-zp-cite%3D%26%23039%3Bapi_user_id%3D2323737%26amp%3Bitem_key%3DD49PS9IT%26%23039%3B%20href%3D%26%23039%3Bjavascript%3Avoid%280%29%3B%26%23039%3B%26gt%3BCite%26lt%3B%5C%2Fa%26gt%3B%20%26lt%3B%5C%2Fdiv%26gt%3B%5Cn%26lt%3B%5C%2Fdiv%26gt%3B%22%2C%22data%22%3A%7B%22itemType%22%3A%22journalArticle%22%2C%22title%22%3A%22Sequential%20transcriptional%20waves%20and%20NF-%5Cu03baB-driven%20chromatin%20remodeling%20direct%20drug-induced%20dedifferentiation%20in%20cancer%22%2C%22creators%22%3A%5B%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Yapeng%22%2C%22lastName%22%3A%22Su%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Chunmei%22%2C%22lastName%22%3A%22Liu%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Xiang%22%2C%22lastName%22%3A%22Lu%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Hui-Yu%22%2C%22lastName%22%3A%22Chuang%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Guideng%22%2C%22lastName%22%3A%22Li%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Shiqun%22%2C%22lastName%22%3A%22Shao%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Yan%22%2C%22lastName%22%3A%22Kong%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Jihoon%20W.%22%2C%22lastName%22%3A%22Lee%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Rachel%20H.%22%2C%22lastName%22%3A%22Ng%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Stephanie%22%2C%22lastName%22%3A%22Wong%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Lidia%22%2C%22lastName%22%3A%22Robert%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Charles%22%2C%22lastName%22%3A%22Warden%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Victoria%22%2C%22lastName%22%3A%22Liu%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Jie%22%2C%22lastName%22%3A%22Chen%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Zhuo%22%2C%22lastName%22%3A%22Wang%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Guangrong%22%2C%22lastName%22%3A%22Qin%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Yin%22%2C%22lastName%22%3A%22Tang%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Hanjun%22%2C%22lastName%22%3A%22Cheng%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Alphonsus%20H.%20C.%22%2C%22lastName%22%3A%22Ng%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Daniel%22%2C%22lastName%22%3A%22Chen%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Songming%22%2C%22lastName%22%3A%22Peng%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Min%22%2C%22lastName%22%3A%22Xue%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Dazy%22%2C%22lastName%22%3A%22Johnson%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Yu%22%2C%22lastName%22%3A%22Xu%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Jinhui%22%2C%22lastName%22%3A%22Wang%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Xiwei%22%2C%22lastName%22%3A%22Wu%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Ilya%22%2C%22lastName%22%3A%22Shmulevich%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Qihui%22%2C%22lastName%22%3A%22Shi%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Raphael%22%2C%22lastName%22%3A%22Levine%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Antoni%22%2C%22lastName%22%3A%22Ribas%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22David%22%2C%22lastName%22%3A%22Baltimore%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Jun%22%2C%22lastName%22%3A%22Guo%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22James%20R.%22%2C%22lastName%22%3A%22Heath%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Wei%22%2C%22lastName%22%3A%22Wei%22%7D%5D%2C%22abstractNote%22%3A%22Drug-induced%20dedifferentiation%20towards%20drug-tolerant%20persister%20states%20is%20a%20common%20mechanism%20cancer%20cells%20exploit%20to%20escape%20therapies%2C%20hindering%20durable%20responses.%20How%20early%20epigenomic%20and%20transcriptomic%20programs%20coordinate%20to%20initiate%20these%20reversible%20transitions%20remains%20largely%20unexplored.%20Here%20we%20employ%20high-temporal-resolution%20multi-omics%20profiling%2C%20information-theoretic%20approaches%2C%20and%20dynamic%20system%20modeling%20to%20probe%20these%20processes%20in%20BRAF-mutant%20melanoma%20models%20and%20patient%20specimens.%20We%20uncover%20a%20hysteretic%20transition%20trajectory%20in%20response%20to%20oncogene%20inhibition%20and%20subsequent%20release%2C%20driven%20by%20two%20tightly%20coupled%20transcriptional%20waves%20that%20orchestrate%20genome-scale%20chromatin%20reconfiguration.%20Modeling%20of%20these%20waves%20suggests%20NF-%5Cu03baB%5C%2FRelA-driven%20chromatin%20remodeling%20as%20the%20underlying%20mechanism%20of%20cell-state%20dedifferentiation%2C%20which%20we%20validate%20experimentally.%20We%20identify%20RelA-target%20genes%20epigenetically%20modulated%20to%20drive%20this%20process%20and%20define%20a%20quantitative%20epigenome%20gauge%20of%20melanoma%20cell-state%20plasticity%20that%20supports%20targeting%20epigenetic%20machineries%20to%20potentiate%20oncogene%20inhibition.%20Across%20additional%20cancer%20models%2C%20oxidative%20stress-mediated%20NF-%5Cu03baB%5C%2FRelA%20activation%20emerges%20as%20a%20common%20driver%20of%20transitions%20into%20drug-tolerant%20persister%20states%2C%20revealing%20a%20central%20role%20for%20NF-%5Cu03baB%20axis%20in%20coupling%20oxidative%20stress%20to%20cancer%20progression.%22%2C%22date%22%3A%222026%22%2C%22section%22%3A%22%22%2C%22partNumber%22%3A%22%22%2C%22partTitle%22%3A%22%22%2C%22DOI%22%3A%2210.1038%5C%2Fs41467-026-71349-4%22%2C%22citationKey%22%3A%22%22%2C%22url%22%3A%22https%3A%5C%2F%5C%2Fwww.nature.com%5C%2Farticles%5C%2Fs41467-026-71349-4%22%2C%22PMID%22%3A%22%22%2C%22PMCID%22%3A%22%22%2C%22ISSN%22%3A%222041-1723%22%2C%22language%22%3A%22en%22%2C%22collections%22%3A%5B%222RQKSFR5%22%5D%2C%22dateModified%22%3A%222026-04-15T13%3A48%3A22Z%22%7D%7D%2C%7B%22key%22%3A%222HVF3BMH%22%2C%22library%22%3A%7B%22id%22%3A2323737%7D%2C%22meta%22%3A%7B%22creatorSummary%22%3A%22Wang%20et%20al.%22%2C%22parsedDate%22%3A%222026%22%2C%22numChildren%22%3A1%7D%2C%22bib%22%3A%22%26lt%3Bdiv%20class%3D%26quot%3Bcsl-bib-body%26quot%3B%20style%3D%26quot%3Bline-height%3A%201.35%3B%20padding-left%3A%201em%3B%20text-indent%3A-1em%3B%26quot%3B%26gt%3B%5Cn%20%20%26lt%3Bdiv%20class%3D%26quot%3Bcsl-entry%26quot%3B%26gt%3BWang%2C%20Zhuo%2C%20Qing%20Luo%2C%20Jie%20Wu%2C%20Li%20Lu%2C%20Wenjie%20Ding%2C%20Yichun%20Zhao%2C%20Yongfeng%20Yu%2C%20et%20al.%202026.%20%26%23x201C%3BSpatial%20Multi-Omics%20Unveils%20the%20Monoclonal%20Origin%2C%20Neuroendocrine%20Plasticity%2C%20and%20Microenvironment%20Niches%20in%20Combined%20Small-Cell%20Lung%20Cancer.%26%23x201D%3B%20%26lt%3Bi%26gt%3BCell%20Reports%20Medicine%26lt%3B%5C%2Fi%26gt%3B%200%20%280%29.%20Elsevier.%20%26lt%3Ba%20class%3D%26%23039%3Bzp-DOIURL%26%23039%3B%20href%3D%26%23039%3Bhttp%3A%5C%2F%5C%2Fdoi.org%5C%2F10.1016%5C%2Fj.xcrm.2026.102741%26%23039%3B%26gt%3Bhttp%3A%5C%2F%5C%2Fdoi.org%5C%2F10.1016%5C%2Fj.xcrm.2026.102741%26lt%3B%5C%2Fa%26gt%3B.%20%26lt%3Ba%20title%3D%26%23039%3BCite%20in%20RIS%20Format%26%23039%3B%20class%3D%26%23039%3Bzp-CiteRIS%26%23039%3B%20data-zp-cite%3D%26%23039%3Bapi_user_id%3D2323737%26amp%3Bitem_key%3D2HVF3BMH%26%23039%3B%20href%3D%26%23039%3Bjavascript%3Avoid%280%29%3B%26%23039%3B%26gt%3BCite%26lt%3B%5C%2Fa%26gt%3B%20%26lt%3B%5C%2Fdiv%26gt%3B%5Cn%26lt%3B%5C%2Fdiv%26gt%3B%22%2C%22data%22%3A%7B%22itemType%22%3A%22journalArticle%22%2C%22title%22%3A%22Spatial%20multi-omics%20unveils%20the%20monoclonal%20origin%2C%20neuroendocrine%20plasticity%2C%20and%20microenvironment%20niches%20in%20combined%20small-cell%20lung%20cancer%22%2C%22creators%22%3A%5B%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Zhuo%22%2C%22lastName%22%3A%22Wang%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Qing%22%2C%22lastName%22%3A%22Luo%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Jie%22%2C%22lastName%22%3A%22Wu%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Li%22%2C%22lastName%22%3A%22Lu%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Wenjie%22%2C%22lastName%22%3A%22Ding%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Yichun%22%2C%22lastName%22%3A%22Zhao%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Yongfeng%22%2C%22lastName%22%3A%22Yu%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Ruoran%22%2C%22lastName%22%3A%22Qiu%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Ling%22%2C%22lastName%22%3A%22Zhu%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Xinxing%22%2C%22lastName%22%3A%22Ouyang%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Wendi%22%2C%22lastName%22%3A%22Xuzhang%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Shun%22%2C%22lastName%22%3A%22Lu%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Wei%22%2C%22lastName%22%3A%22Wei%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Qihui%22%2C%22lastName%22%3A%22Shi%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Ziming%22%2C%22lastName%22%3A%22Li%22%7D%5D%2C%22abstractNote%22%3A%22%22%2C%22date%22%3A%222026%22%2C%22section%22%3A%22%22%2C%22partNumber%22%3A%22%22%2C%22partTitle%22%3A%22%22%2C%22DOI%22%3A%2210.1016%5C%2Fj.xcrm.2026.102741%22%2C%22citationKey%22%3A%22%22%2C%22url%22%3A%22https%3A%5C%2F%5C%2Fwww.cell.com%5C%2Fcell-reports-medicine%5C%2Fabstract%5C%2FS2666-3791%2826%2900158-8%22%2C%22PMID%22%3A%22%22%2C%22PMCID%22%3A%22%22%2C%22ISSN%22%3A%222666-3791%22%2C%22language%22%3A%22English%22%2C%22collections%22%3A%5B%222RQKSFR5%22%5D%2C%22dateModified%22%3A%222026-04-10T17%3A48%3A48Z%22%7D%7D%2C%7B%22key%22%3A%227FU8PGD8%22%2C%22library%22%3A%7B%22id%22%3A2323737%7D%2C%22meta%22%3A%7B%22creatorSummary%22%3A%22Wang%20et%20al.%22%2C%22parsedDate%22%3A%222026%22%2C%22numChildren%22%3A1%7D%2C%22bib%22%3A%22%26lt%3Bdiv%20class%3D%26quot%3Bcsl-bib-body%26quot%3B%20style%3D%26quot%3Bline-height%3A%201.35%3B%20padding-left%3A%201em%3B%20text-indent%3A-1em%3B%26quot%3B%26gt%3B%5Cn%20%20%26lt%3Bdiv%20class%3D%26quot%3Bcsl-entry%26quot%3B%26gt%3BWang%2C%20Zhuo%2C%20Qing%20Luo%2C%20Jie%20Wu%2C%20Wei%20Wei%2C%20Li%20Lu%2C%20Wenjie%20Ding%2C%20Yichun%20Zhao%2C%20et%20al.%202026.%20%26%23x201C%3BSpatial%20Multi-Omics%20Unveils%20the%20Monoclonal%20Origin%2C%20Neuroendocrine%20Plasticity%2C%20and%20Microenvironment%20Niches%20in%20Combined%20Small%20Cell%20Lung%20Cancer.%26%23x201D%3B%20bioRxiv.%20%26lt%3Ba%20class%3D%26%23039%3Bzp-DOIURL%26%23039%3B%20href%3D%26%23039%3Bhttp%3A%5C%2F%5C%2Fdoi.org%5C%2F10.64898%5C%2F2026.01.31.702982%26%23039%3B%26gt%3Bhttp%3A%5C%2F%5C%2Fdoi.org%5C%2F10.64898%5C%2F2026.01.31.702982%26lt%3B%5C%2Fa%26gt%3B.%20%26lt%3Ba%20title%3D%26%23039%3BCite%20in%20RIS%20Format%26%23039%3B%20class%3D%26%23039%3Bzp-CiteRIS%26%23039%3B%20data-zp-cite%3D%26%23039%3Bapi_user_id%3D2323737%26amp%3Bitem_key%3D7FU8PGD8%26%23039%3B%20href%3D%26%23039%3Bjavascript%3Avoid%280%29%3B%26%23039%3B%26gt%3BCite%26lt%3B%5C%2Fa%26gt%3B%20%26lt%3B%5C%2Fdiv%26gt%3B%5Cn%26lt%3B%5C%2Fdiv%26gt%3B%22%2C%22data%22%3A%7B%22itemType%22%3A%22preprint%22%2C%22title%22%3A%22Spatial%20multi-omics%20unveils%20the%20monoclonal%20origin%2C%20neuroendocrine%20plasticity%2C%20and%20microenvironment%20niches%20in%20combined%20small%20cell%20lung%20cancer%22%2C%22creators%22%3A%5B%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Zhuo%22%2C%22lastName%22%3A%22Wang%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Qing%22%2C%22lastName%22%3A%22Luo%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Jie%22%2C%22lastName%22%3A%22Wu%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Wei%22%2C%22lastName%22%3A%22Wei%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Li%22%2C%22lastName%22%3A%22Lu%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Wenjie%22%2C%22lastName%22%3A%22Ding%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Yichun%22%2C%22lastName%22%3A%22Zhao%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Yongfeng%22%2C%22lastName%22%3A%22Yu%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Ruoran%22%2C%22lastName%22%3A%22Qiu%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Ling%22%2C%22lastName%22%3A%22Zhu%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Xinxing%22%2C%22lastName%22%3A%22Ouyang%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Wendi%22%2C%22lastName%22%3A%22Xuzhang%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Shun%22%2C%22lastName%22%3A%22Lu%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Qihui%22%2C%22lastName%22%3A%22Shi%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Ziming%22%2C%22lastName%22%3A%22Li%22%7D%5D%2C%22abstractNote%22%3A%22Combined%20small-cell%20lung%20cancer%20%28cSCLC%29%20is%20a%20rare%20and%20aggressive%20subtype%20of%20small-cell%20lung%20cancer%20%28SCLC%29%20characterized%20by%20mixed%20histology%20comprising%20SCLC%20and%20non-small%20cell%20lung%20cancer%20%28NSCLC%29%20or%20large%20cell%20neuroendocrine%20carcinoma%20%28LCNEC%29%20components.%20Despite%20its%20histological%20heterogeneity%20and%20even%20poorer%20prognosis%20than%20de%20novo%20SCLC%2C%20cSCLC%20is%20clinically%20managed%20as%20pure%20SCLC%2C%20largely%20due%20to%20the%20lack%20of%20molecular%20insights%20into%20its%20biology%2C%20lineage%20plasticity%2C%20and%20tumor%20microenvironment%20%28TME%29.%20Here%2C%20we%20perform%20multi-omics%20profiling%2C%20including%20spatially-resolved%20whole-exome%20sequencing%20%28WES%29%2C%20spatial%20transcriptomics%20%28ST%29%20and%20single-nucleus%20RNA%20sequencing%20%28snRNA-seq%29%2C%20across%2019%20treatment-na%5Cu00efve%20cSCLC%20tumors%20spanning%20all%20major%20histological%20subtypes.%20Our%20analysis%20reveals%20that%20SCLC%20and%20NSCLC%5C%2FLCNEC%20components%20share%20a%20monoclonal%20origin%2C%20with%20histological%20divergence%20characterized%20by%20distinct%20mutation%20and%20copy%20number%20alteration%20patterns.%20ST%20and%20snRNA-seq%20uncover%20spatially%20exclusive%20or%20interspersed%20tumor%20domains%2C%20with%20distinct%20TME%20compositions%20and%20immune%20landscapes.%20Notably%2C%20fibroblast-rich%20regions%20enriched%20for%20an%20aggressive%20fibroblast%20subtype%20form%20boundaries%20between%20tumor%20domains%2C%20potentially%20influencing%20immune%20TME%20and%20treatment%20responses.%20We%20identify%20extensive%20lineage%20plasticity%20within%20cSCLC%2C%20including%20active%20LUAD-to-SCLC%20transdifferentiation%20and%20SCLC%20subtype%20coexistence%2C%20suggesting%20transitional%20cellular%20states%20not%20captured%20by%20traditional%20diagnostics.%20Leveraging%20these%20insights%2C%20we%20developed%20the%20cSCLC%20Detector%2C%20a%20sensitive%20mutation-based%20diagnostic%20assay%20that%20improves%20the%20detection%20of%20cSCLC%20in%20tissue%20and%20liquid%20biopsy%20samples.%20Our%20findings%20offer%20critical%20insights%20into%20cSCLC%20lineage%20plasticity%2C%20cellular%20evolution%2C%20and%20microenvironmental%20interactions%2C%20underscoring%20the%20need%20for%20tailored%20treatment%20strategies%20and%20diagnostic%20frameworks%20for%20this%20aggressive%20cancer%20subtype.%22%2C%22genre%22%3A%22%22%2C%22repository%22%3A%22bioRxiv%22%2C%22archiveID%22%3A%22%22%2C%22date%22%3A%222026%22%2C%22DOI%22%3A%2210.64898%5C%2F2026.01.31.702982%22%2C%22citationKey%22%3A%22%22%2C%22url%22%3A%22https%3A%5C%2F%5C%2Fwww.biorxiv.org%5C%2Fcontent%5C%2F10.64898%5C%2F2026.01.31.702982v1%22%2C%22language%22%3A%22en%22%2C%22collections%22%3A%5B%222RQKSFR5%22%5D%2C%22dateModified%22%3A%222026-02-07T00%3A47%3A03Z%22%7D%7D%2C%7B%22key%22%3A%22BUAZSZBI%22%2C%22library%22%3A%7B%22id%22%3A2323737%7D%2C%22meta%22%3A%7B%22creatorSummary%22%3A%22Yan%20et%20al.%22%2C%22parsedDate%22%3A%222025%22%2C%22numChildren%22%3A1%7D%2C%22bib%22%3A%22%26lt%3Bdiv%20class%3D%26quot%3Bcsl-bib-body%26quot%3B%20style%3D%26quot%3Bline-height%3A%201.35%3B%20padding-left%3A%201em%3B%20text-indent%3A-1em%3B%26quot%3B%26gt%3B%5Cn%20%20%26lt%3Bdiv%20class%3D%26quot%3Bcsl-entry%26quot%3B%26gt%3BYan%2C%20Xiaowei%2C%20Zhuo%20Wang%2C%20Ziming%20Li%2C%20Yichun%20Zhao%2C%20Shun%20Lu%2C%20Qihui%20Shi%2C%20and%20Wei%20Wei.%202025.%20%26%23x201C%3BDTCFinder%3A%20A%20Bench-to-Bits%20Toolkit%20for%20Label-Free%2C%20Whole-Spectrum%20Analysis%20of%20Disseminated%20and%20Circulating%20Tumor%20Cells%20in%20Liquid%20Biopsies.%26%23x201D%3B%20bioRxiv.%20%26lt%3Ba%20class%3D%26%23039%3Bzp-DOIURL%26%23039%3B%20href%3D%26%23039%3Bhttp%3A%5C%2F%5C%2Fdoi.org%5C%2F10.1101%5C%2F2025.11.27.690914%26%23039%3B%26gt%3Bhttp%3A%5C%2F%5C%2Fdoi.org%5C%2F10.1101%5C%2F2025.11.27.690914%26lt%3B%5C%2Fa%26gt%3B.%20%26lt%3Ba%20title%3D%26%23039%3BCite%20in%20RIS%20Format%26%23039%3B%20class%3D%26%23039%3Bzp-CiteRIS%26%23039%3B%20data-zp-cite%3D%26%23039%3Bapi_user_id%3D2323737%26amp%3Bitem_key%3DBUAZSZBI%26%23039%3B%20href%3D%26%23039%3Bjavascript%3Avoid%280%29%3B%26%23039%3B%26gt%3BCite%26lt%3B%5C%2Fa%26gt%3B%20%26lt%3B%5C%2Fdiv%26gt%3B%5Cn%26lt%3B%5C%2Fdiv%26gt%3B%22%2C%22data%22%3A%7B%22itemType%22%3A%22preprint%22%2C%22title%22%3A%22DTCFinder%3A%20a%20bench-to-bits%20toolkit%20for%20label-free%2C%20whole-spectrum%20analysis%20of%20disseminated%20and%20circulating%20tumor%20cells%20in%20liquid%20biopsies%22%2C%22creators%22%3A%5B%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Xiaowei%22%2C%22lastName%22%3A%22Yan%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Zhuo%22%2C%22lastName%22%3A%22Wang%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Ziming%22%2C%22lastName%22%3A%22Li%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Yichun%22%2C%22lastName%22%3A%22Zhao%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Shun%22%2C%22lastName%22%3A%22Lu%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Qihui%22%2C%22lastName%22%3A%22Shi%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Wei%22%2C%22lastName%22%3A%22Wei%22%7D%5D%2C%22abstractNote%22%3A%22Disseminated%20%28DTCs%29%20and%20circulating%20tumor%20cells%20%28CTCs%29%20are%20rare%20but%20pivotal%20in%20understanding%20cancer%20metastasis%20and%20advancing%20liquid%20biopsy-based%20diagnostics.%20Traditional%20detection%20approaches%2C%20hindered%20by%20their%20dependency%20on%20epithelial%20markers%20or%20morphological%20features%2C%20impair%20the%20accurate%20identification%20of%20varied%20DTC%5C%2FCTC%20phenotypes%20within%20liquid%20biopsies.%20We%20describe%20DTCFinder%2C%20a%20bench-to-bits%2C%20label-free%20method%20integrating%20high-throughput%20single-cell%20RNA%20sequencing%20and%20machine%20learning%2C%20enabling%20unbiased%20detection%2C%20in-depth%20molecular%20characterization%2C%20and%20precise%20tissue-of-origin%20tracing%20of%20DTCs%5C%2FCTCs%20across%20various%20types%20of%20liquid%20biopsies%2C%20even%20with%20ultra-scarce%20DTC%5C%2FCTC%20presence%20in%20peripheral%20blood%20and%20low%20sequencing%20depth.%20DTCFinder%20offers%20a%20robust%20and%20versatile%20toolkit%20for%20liquid%20biopsy-based%20cancer%20diagnostics%2C%20enhancing%20our%20understanding%20of%20cancer%20metastasis.%22%2C%22genre%22%3A%22%22%2C%22repository%22%3A%22bioRxiv%22%2C%22archiveID%22%3A%22%22%2C%22date%22%3A%222025%22%2C%22DOI%22%3A%2210.1101%5C%2F2025.11.27.690914%22%2C%22citationKey%22%3A%22%22%2C%22url%22%3A%22https%3A%5C%2F%5C%2Fwww.biorxiv.org%5C%2Fcontent%5C%2F10.1101%5C%2F2025.11.27.690914v1%22%2C%22language%22%3A%22en%22%2C%22collections%22%3A%5B%222RQKSFR5%22%5D%2C%22dateModified%22%3A%222026-01-09T18%3A25%3A44Z%22%7D%7D%2C%7B%22key%22%3A%22SMQ5RBSJ%22%2C%22library%22%3A%7B%22id%22%3A2323737%7D%2C%22meta%22%3A%7B%22creatorSummary%22%3A%22Flower%20et%20al.%22%2C%22parsedDate%22%3A%222025%22%2C%22numChildren%22%3A1%7D%2C%22bib%22%3A%22%26lt%3Bdiv%20class%3D%26quot%3Bcsl-bib-body%26quot%3B%20style%3D%26quot%3Bline-height%3A%201.35%3B%20padding-left%3A%201em%3B%20text-indent%3A-1em%3B%26quot%3B%26gt%3B%5Cn%20%20%26lt%3Bdiv%20class%3D%26quot%3Bcsl-entry%26quot%3B%26gt%3BFlower%2C%20Cameron%20T.%2C%20Chunmei%20Liu%2C%20Hui-Yu%20Chuang%2C%20Xiaoyang%20Ye%2C%20Hanjun%20Cheng%2C%20James%20R.%20Heath%2C%20Wei%20Wei%2C%20and%20Forest%20M.%20White.%202025.%20%26%23x201C%3BSignaling%20and%20Transcriptional%20Dynamics%20Underlying%20Early%20Adaptation%20to%20Oncogenic%20BRAF%20Inhibition.%26%23x201D%3B%20%26lt%3Bi%26gt%3BCell%20Systems%26lt%3B%5C%2Fi%26gt%3B%2C%20101239.%20%26lt%3Ba%20class%3D%26%23039%3Bzp-DOIURL%26%23039%3B%20href%3D%26%23039%3Bhttp%3A%5C%2F%5C%2Fdoi.org%5C%2F10.1016%5C%2Fj.cels.2025.101239%26%23039%3B%26gt%3Bhttp%3A%5C%2F%5C%2Fdoi.org%5C%2F10.1016%5C%2Fj.cels.2025.101239%26lt%3B%5C%2Fa%26gt%3B.%20%26lt%3Ba%20title%3D%26%23039%3BCite%20in%20RIS%20Format%26%23039%3B%20class%3D%26%23039%3Bzp-CiteRIS%26%23039%3B%20data-zp-cite%3D%26%23039%3Bapi_user_id%3D2323737%26amp%3Bitem_key%3DSMQ5RBSJ%26%23039%3B%20href%3D%26%23039%3Bjavascript%3Avoid%280%29%3B%26%23039%3B%26gt%3BCite%26lt%3B%5C%2Fa%26gt%3B%20%26lt%3B%5C%2Fdiv%26gt%3B%5Cn%26lt%3B%5C%2Fdiv%26gt%3B%22%2C%22data%22%3A%7B%22itemType%22%3A%22journalArticle%22%2C%22title%22%3A%22Signaling%20and%20transcriptional%20dynamics%20underlying%20early%20adaptation%20to%20oncogenic%20BRAF%20inhibition%22%2C%22creators%22%3A%5B%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Cameron%20T.%22%2C%22lastName%22%3A%22Flower%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Chunmei%22%2C%22lastName%22%3A%22Liu%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Hui-Yu%22%2C%22lastName%22%3A%22Chuang%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Xiaoyang%22%2C%22lastName%22%3A%22Ye%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Hanjun%22%2C%22lastName%22%3A%22Cheng%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22James%20R.%22%2C%22lastName%22%3A%22Heath%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Wei%22%2C%22lastName%22%3A%22Wei%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Forest%20M.%22%2C%22lastName%22%3A%22White%22%7D%5D%2C%22abstractNote%22%3A%22A%20major%20contributor%20to%20poor%20sensitivity%20to%20anti-cancer%20kinase%20inhibitor%20therapy%20is%20drug-induced%20cellular%20adaptation%2C%20whereby%20remodeling%20of%20signaling%20and%20gene%20regulatory%20networks%20permits%20a%20drug-tolerant%20phenotype.%20Here%2C%20we%20resolve%20the%20scale%20and%20kinetics%20of%20critical%20subcellular%20events%20following%20oncogenic%20kinase%20inhibition%20and%20preceding%20cell%20cycle%20re-entry%2C%20using%20mass%20spectrometry-based%20phosphoproteomics%20and%20RNA%20sequencing%20%28RNA-seq%29%20to%20monitor%20the%20dynamics%20of%20thousands%20of%20growth-%20and%20survival-related%20signals%20over%20the%20first%20minutes%2C%20hours%2C%20and%20days%20of%20oncogenic%20BRAF%20inhibition%20in%20human%20melanoma%20cells.%20We%20observed%20sustained%20inhibition%20of%20the%20BRAF-ERK%20axis%2C%20gradual%20downregulation%20of%20cell%20cycle%20signaling%2C%20and%20three%20distinct%2C%20reversible%20phase%20transitions%20toward%20quiescence.%20Statistical%20inference%20of%20kinetically%20defined%20regulatory%20modules%20revealed%20a%20dominant%20compensatory%20induction%20of%20SRC%20family%20kinase%20%28SFK%29%20signaling%2C%20promoted%20in%20part%20by%20excess%20reactive%20oxygen%20species%2C%20rendering%20cells%20sensitive%20to%20co-treatment%20with%20an%20SFK%20inhibitor%20in%5Cu00a0vitro%20and%20in%5Cu00a0vivo%2C%20underscoring%20the%20translational%20potential%20for%20assessing%20early%20drug-induced%20adaptive%20signaling.%20A%20record%20of%20this%20paper%5Cu2019s%20transparent%20peer%20review%20process%20is%20included%20in%20the%20supplemental%20information.%22%2C%22date%22%3A%222025%22%2C%22section%22%3A%22%22%2C%22partNumber%22%3A%22%22%2C%22partTitle%22%3A%22%22%2C%22DOI%22%3A%2210.1016%5C%2Fj.cels.2025.101239%22%2C%22citationKey%22%3A%22%22%2C%22url%22%3A%22https%3A%5C%2F%5C%2Fwww.sciencedirect.com%5C%2Fscience%5C%2Farticle%5C%2Fpii%5C%2FS2405471225000729%22%2C%22PMID%22%3A%22%22%2C%22PMCID%22%3A%22%22%2C%22ISSN%22%3A%222405-4712%22%2C%22language%22%3A%22%22%2C%22collections%22%3A%5B%222RQKSFR5%22%5D%2C%22dateModified%22%3A%222025-03-24T18%3A45%3A40Z%22%7D%7D%2C%7B%22key%22%3A%22WEQXDYM9%22%2C%22library%22%3A%7B%22id%22%3A2323737%7D%2C%22meta%22%3A%7B%22creatorSummary%22%3A%22Kim%20et%20al.%22%2C%22parsedDate%22%3A%222024%22%2C%22numChildren%22%3A1%7D%2C%22bib%22%3A%22%26lt%3Bdiv%20class%3D%26quot%3Bcsl-bib-body%26quot%3B%20style%3D%26quot%3Bline-height%3A%201.35%3B%20padding-left%3A%201em%3B%20text-indent%3A-1em%3B%26quot%3B%26gt%3B%5Cn%20%20%26lt%3Bdiv%20class%3D%26quot%3Bcsl-entry%26quot%3B%26gt%3BKim%2C%20Jungwoo%2C%20Rachel%20H.%20Ng%2C%20JingXin%20Liang%2C%20Dazy%20Johnson%2C%20Young%20Shik%20Shin%2C%20Arion%20F.%20Chatziioannou%2C%20Michael%20E.%20Phelps%2C%20Wei%20Wei%2C%20Raphael%20D.%20Levine%2C%20and%20James%20R.%20Heath.%202024.%20%26%23x201C%3BKinetic%20Trajectories%20of%20Glucose%20Uptake%20in%20Single%20Cancer%20Cells%20Reveal%20a%20Drug-Induced%20Cell-State%20Change%20Within%20Hours%20of%20Drug%20Treatment.%26%23x201D%3B%20%26lt%3Bi%26gt%3BThe%20Journal%20of%20Physical%20Chemistry.%20B%26lt%3B%5C%2Fi%26gt%3B.%20%26lt%3Ba%20class%3D%26%23039%3Bzp-DOIURL%26%23039%3B%20href%3D%26%23039%3Bhttp%3A%5C%2F%5C%2Fdoi.org%5C%2F10.1021%5C%2Facs.jpcb.4c03663%26%23039%3B%26gt%3Bhttp%3A%5C%2F%5C%2Fdoi.org%5C%2F10.1021%5C%2Facs.jpcb.4c03663%26lt%3B%5C%2Fa%26gt%3B.%20%26lt%3Ba%20title%3D%26%23039%3BCite%20in%20RIS%20Format%26%23039%3B%20class%3D%26%23039%3Bzp-CiteRIS%26%23039%3B%20data-zp-cite%3D%26%23039%3Bapi_user_id%3D2323737%26amp%3Bitem_key%3DWEQXDYM9%26%23039%3B%20href%3D%26%23039%3Bjavascript%3Avoid%280%29%3B%26%23039%3B%26gt%3BCite%26lt%3B%5C%2Fa%26gt%3B%20%26lt%3B%5C%2Fdiv%26gt%3B%5Cn%26lt%3B%5C%2Fdiv%26gt%3B%22%2C%22data%22%3A%7B%22itemType%22%3A%22journalArticle%22%2C%22title%22%3A%22Kinetic%20Trajectories%20of%20Glucose%20Uptake%20in%20Single%20Cancer%20Cells%20Reveal%20a%20Drug-Induced%20Cell-State%20Change%20Within%20Hours%20of%20Drug%20Treatment%22%2C%22creators%22%3A%5B%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Jungwoo%22%2C%22lastName%22%3A%22Kim%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Rachel%20H.%22%2C%22lastName%22%3A%22Ng%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22JingXin%22%2C%22lastName%22%3A%22Liang%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Dazy%22%2C%22lastName%22%3A%22Johnson%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Young%20Shik%22%2C%22lastName%22%3A%22Shin%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Arion%20F.%22%2C%22lastName%22%3A%22Chatziioannou%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Michael%20E.%22%2C%22lastName%22%3A%22Phelps%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Wei%22%2C%22lastName%22%3A%22Wei%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Raphael%20D.%22%2C%22lastName%22%3A%22Levine%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22James%20R.%22%2C%22lastName%22%3A%22Heath%22%7D%5D%2C%22abstractNote%22%3A%22The%20development%20of%20drug%20resistance%20is%20a%20nearly%20universal%20phenomenon%20in%20patients%20with%20glioblastoma%20multiforme%20%28GBM%29%20brain%20tumors.%20Upon%20treatment%2C%20GBM%20cancer%20cells%20may%20initially%20undergo%20a%20drug-induced%20cell-state%20change%20to%20a%20drug-tolerant%2C%20slow-cycling%20state.%20The%20kinetics%20of%20that%20process%20are%20not%20well%20understood%2C%20in%20part%20due%20to%20the%20heterogeneity%20of%20GBM%20tumors%20and%20tumor%20models%2C%20which%20can%20confound%20the%20interpretation%20of%20kinetic%20data.%20Here%2C%20we%20resolve%20drug-adaptation%20kinetics%20in%20a%20patient-derived%20in%20vitro%20GBM%20tumor%20model%20characterized%20by%20the%20epithelial%20growth%20factor%20receptor%20%28EGFR%29%20variant%28v%29III%20oncogene%20treated%20with%20an%20EGFR%20inhibitor.%20We%20use%20radiolabeled%2018F-fluorodeoxyglucose%20%28FDG%29%20to%20monitor%20the%20glucose%20uptake%20trajectories%20of%20single%20GBM%20cancer%20cells%20over%20a%2012%20h%20period%20of%20drug%20treatment.%20Autocorrelation%20analysis%20of%20the%20single-cell%20glucose%20uptake%20trajectories%20reveals%20evidence%20of%20a%20drug-induced%20cell-state%20change%20from%20a%20high-%20to%20low-glycolytic%20phenotype%20after%205-7%20h%20of%20drug%20treatment.%20Information%20theoretic%20analysis%20of%20a%20bulk%20transcriptome%20kinetic%20series%20of%20the%20GBM%20tumor%20model%20delineated%20the%20underlying%20molecular%20mechanisms%20driving%20the%20cellular%20state%20change%2C%20including%20a%20shift%20from%20a%20stem-like%20mesenchymal%20state%20to%20a%20more%20differentiated%2C%20slow-cycling%20astrocyte-like%20state.%20Our%20results%20demonstrate%20that%20complex%20drug-induced%20cancer%20cell-state%20changes%20of%20cancer%20cells%20can%20be%20captured%20via%20measurements%20of%20single%20cell%20metabolic%20trajectories%20and%20reveal%20the%20extremely%20facile%20nature%20of%20drug%20adaptation.%22%2C%22date%22%3A%222024%22%2C%22section%22%3A%22%22%2C%22partNumber%22%3A%22%22%2C%22partTitle%22%3A%22%22%2C%22DOI%22%3A%2210.1021%5C%2Facs.jpcb.4c03663%22%2C%22citationKey%22%3A%22%22%2C%22url%22%3A%22%22%2C%22PMID%22%3A%2239115241%22%2C%22PMCID%22%3A%22%22%2C%22ISSN%22%3A%221520-5207%22%2C%22language%22%3A%22eng%22%2C%22collections%22%3A%5B%222RQKSFR5%22%5D%2C%22dateModified%22%3A%222024-08-08T19%3A44%3A30Z%22%7D%7D%2C%7B%22key%22%3A%22DGUNZAY3%22%2C%22library%22%3A%7B%22id%22%3A2323737%7D%2C%22meta%22%3A%7B%22creatorSummary%22%3A%22Yang%20et%20al.%22%2C%22parsedDate%22%3A%222024%22%2C%22numChildren%22%3A0%7D%2C%22bib%22%3A%22%26lt%3Bdiv%20class%3D%26quot%3Bcsl-bib-body%26quot%3B%20style%3D%26quot%3Bline-height%3A%201.35%3B%20padding-left%3A%201em%3B%20text-indent%3A-1em%3B%26quot%3B%26gt%3B%5Cn%20%20%26lt%3Bdiv%20class%3D%26quot%3Bcsl-entry%26quot%3B%26gt%3BYang%2C%20Liwei%2C%20Juho%20Kim%2C%20Long%20Chen%2C%20Wei%20Wei%2C%20and%20Jun%20Wang.%202024.%20%26%23x201C%3BDetection%20of%20%26gt%3B400%20Cluster%20of%20Differentiation%20Biomarkers%20and%20Pathway%20Proteins%20in%20Single%20Immune%20Cells%20by%20Cyclic%20Multiplex%20In%20Situ%20Tagging%20for%20Single-Cell%20Proteomic%20Studies.%26%23x201D%3B%20%26lt%3Bi%26gt%3BAnalytical%20Chemistry%26lt%3B%5C%2Fi%26gt%3B%2096%20%2843%29.%20American%20Chemical%20Society%3A%2017387%26%23×2013%3B95.%20%26lt%3Ba%20class%3D%26%23039%3Bzp-DOIURL%26%23039%3B%20href%3D%26%23039%3Bhttp%3A%5C%2F%5C%2Fdoi.org%5C%2F10.1021%5C%2Facs.analchem.4c04239%26%23039%3B%26gt%3Bhttp%3A%5C%2F%5C%2Fdoi.org%5C%2F10.1021%5C%2Facs.analchem.4c04239%26lt%3B%5C%2Fa%26gt%3B.%20%26lt%3Ba%20title%3D%26%23039%3BCite%20in%20RIS%20Format%26%23039%3B%20class%3D%26%23039%3Bzp-CiteRIS%26%23039%3B%20data-zp-cite%3D%26%23039%3Bapi_user_id%3D2323737%26amp%3Bitem_key%3DDGUNZAY3%26%23039%3B%20href%3D%26%23039%3Bjavascript%3Avoid%280%29%3B%26%23039%3B%26gt%3BCite%26lt%3B%5C%2Fa%26gt%3B%20%26lt%3B%5C%2Fdiv%26gt%3B%5Cn%26lt%3B%5C%2Fdiv%26gt%3B%22%2C%22data%22%3A%7B%22itemType%22%3A%22journalArticle%22%2C%22title%22%3A%22Detection%20of%20%3E400%20Cluster%20of%20Differentiation%20Biomarkers%20and%20Pathway%20Proteins%20in%20Single%20Immune%20Cells%20by%20Cyclic%20Multiplex%20In%20Situ%20Tagging%20for%20Single-Cell%20Proteomic%20Studies%22%2C%22creators%22%3A%5B%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Liwei%22%2C%22lastName%22%3A%22Yang%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Juho%22%2C%22lastName%22%3A%22Kim%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Long%22%2C%22lastName%22%3A%22Chen%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Wei%22%2C%22lastName%22%3A%22Wei%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Jun%22%2C%22lastName%22%3A%22Wang%22%7D%5D%2C%22abstractNote%22%3A%22The%20identification%20and%20characterization%20of%20immune%20cell%20subpopulations%20are%20critical%20to%20reveal%20cell%20development%20throughout%20life%20and%20immune%20responses%20to%20environmental%20factors.%20Next-generation%20sequencing%20technologies%20have%20dramatically%20advanced%20single-cell%20genomics%20and%20transcriptomics%20for%20immune%20cell%20classification.%20However%2C%20gene%20expression%20is%20often%20not%20correlated%20with%20protein%20expression%2C%20and%20immunotyping%20is%20mostly%20accepted%20in%20protein%20format.%20Current%20single-cell%20proteomic%20technologies%20are%20either%20limited%20in%20multiplex%20capacity%20or%20not%20sensitive%20enough%20to%20detect%20the%20critical%20functional%20proteins.%20Herein%2C%20we%20present%20a%20single-cell%20cyclic%20multiplex%20in%20situ%20tagging%20%28CycMIST%29%20technology%20to%20simultaneously%20measure%20%26gt%3B400%20proteins%2C%20a%20scale%20of%20%26gt%3B10%20times%20than%20similar%20technologies.%20Such%20an%20ultrahigh%20multiplexity%20is%20achieved%20by%20reiterative%20staining%20of%20the%20single%20cells%20coupled%20with%20a%20MIST%20array%20for%20detection.%20This%20technology%20has%20been%20thoroughly%20validated%20through%20comparison%20with%20flow%20cytometry%20and%20fluorescence%20immunostaining%20techniques.%20Both%20peripheral%20blood%20mononuclear%20cells%20%28PBMCs%29%20and%20T%20cells%20are%20analyzed%20by%20the%20CycMIST%20technology%2C%20and%20almost%20the%20entire%20spectrum%20of%20cluster%20of%20differentiation%20%28CD%29%20surface%20markers%20has%20been%20measured.%20The%20landscape%20of%20fluctuation%20of%20CD%20protein%20expression%20in%20single%20cells%20has%20been%20uncovered%20by%20our%20technology.%20Further%20study%20found%20T%20cell%20activation%20signatures%20and%20protein%5Cu2013protein%20networks.%20This%20study%20represents%20the%20highest%20multiplexity%20of%20single%20immune%20cell%20marker%20measurement%20targeting%20functional%20proteins.%20With%20additional%20information%20from%20intracellular%20proteins%20of%20the%20same%20single%20cells%2C%20our%20technology%20can%20potentially%20facilitate%20mechanistic%20studies%20of%20immune%20responses%20under%20various%20disease%20conditions.%22%2C%22date%22%3A%222024%22%2C%22section%22%3A%22%22%2C%22partNumber%22%3A%22%22%2C%22partTitle%22%3A%22%22%2C%22DOI%22%3A%2210.1021%5C%2Facs.analchem.4c04239%22%2C%22citationKey%22%3A%22%22%2C%22url%22%3A%22https%3A%5C%2F%5C%2Fdoi.org%5C%2F10.1021%5C%2Facs.analchem.4c04239%22%2C%22PMID%22%3A%22%22%2C%22PMCID%22%3A%22%22%2C%22ISSN%22%3A%220003-2700%22%2C%22language%22%3A%22%22%2C%22collections%22%3A%5B%222RQKSFR5%22%5D%2C%22dateModified%22%3A%222025-04-20T21%3A49%3A37Z%22%7D%7D%2C%7B%22key%22%3A%22HX89NNCK%22%2C%22library%22%3A%7B%22id%22%3A2323737%7D%2C%22meta%22%3A%7B%22creatorSummary%22%3A%22Yang%20et%20al.%22%2C%22parsedDate%22%3A%222024%22%2C%22numChildren%22%3A2%7D%2C%22bib%22%3A%22%26lt%3Bdiv%20class%3D%26quot%3Bcsl-bib-body%26quot%3B%20style%3D%26quot%3Bline-height%3A%201.35%3B%20padding-left%3A%201em%3B%20text-indent%3A-1em%3B%26quot%3B%26gt%3B%5Cn%20%20%26lt%3Bdiv%20class%3D%26quot%3Bcsl-entry%26quot%3B%26gt%3BYang%2C%20Liwei%2C%20Juho%20Kim%2C%20Long%20Chen%2C%20Wei%20Wei%2C%20and%20Jun%20Wang.%202024.%20%26%23x201C%3BDetection%20of%20%26gt%3B400%20CD%20Biomarkers%20and%20Pathway%20Proteins%20in%20Single%20Immune%20Cells%20by%20Cyclic%20MIST%20for%20Single-Cell%20Proteomic%20Studies.%26%23x201D%3B%20%26lt%3Bi%26gt%3BAnalytical%20Chemistry%26lt%3B%5C%2Fi%26gt%3B%2096%20%2843%29%3A%2017387%26%23×2013%3B95.%20%26lt%3Ba%20class%3D%26%23039%3Bzp-DOIURL%26%23039%3B%20href%3D%26%23039%3Bhttp%3A%5C%2F%5C%2Fdoi.org%5C%2F10.1021%5C%2Facs.analchem.4c04239%26%23039%3B%26gt%3Bhttp%3A%5C%2F%5C%2Fdoi.org%5C%2F10.1021%5C%2Facs.analchem.4c04239%26lt%3B%5C%2Fa%26gt%3B.%20%26lt%3Ba%20title%3D%26%23039%3BCite%20in%20RIS%20Format%26%23039%3B%20class%3D%26%23039%3Bzp-CiteRIS%26%23039%3B%20data-zp-cite%3D%26%23039%3Bapi_user_id%3D2323737%26amp%3Bitem_key%3DHX89NNCK%26%23039%3B%20href%3D%26%23039%3Bjavascript%3Avoid%280%29%3B%26%23039%3B%26gt%3BCite%26lt%3B%5C%2Fa%26gt%3B%20%26lt%3B%5C%2Fdiv%26gt%3B%5Cn%26lt%3B%5C%2Fdiv%26gt%3B%22%2C%22data%22%3A%7B%22itemType%22%3A%22journalArticle%22%2C%22title%22%3A%22Detection%20of%20%3E400%20CD%20Biomarkers%20and%20Pathway%20Proteins%20in%20Single%20Immune%20Cells%20by%20Cyclic%20MIST%20for%20Single-Cell%20Proteomic%20Studies%22%2C%22creators%22%3A%5B%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Liwei%22%2C%22lastName%22%3A%22Yang%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Juho%22%2C%22lastName%22%3A%22Kim%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Long%22%2C%22lastName%22%3A%22Chen%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Wei%22%2C%22lastName%22%3A%22Wei%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Jun%22%2C%22lastName%22%3A%22Wang%22%7D%5D%2C%22abstractNote%22%3A%22The%20identification%20and%20characterization%20of%20immune%20cell%20subpopulations%20is%20critical%20to%20reveal%20cell%20development%20throughout%20life%20and%20immune%20responses%20to%20environmental%20factors.%20Next-generation%20sequencing%20technologies%20have%20dramatically%20advanced%20single-cell%20genomics%20and%20transcriptomics%20for%20immune%20cell%20classification.%20However%2C%20gene%20expression%20is%20often%20not%20correlated%20with%20protein%20expression%2C%20and%20immunotyping%20is%20mostly%20accepted%20in%20the%20protein%20format.%20Current%20single-cell%20proteomic%20technologies%20are%20either%20limited%20in%20multiplex%20capacity%20or%20not%20sensitive%20enough%20to%20detect%20the%20critical%20functional%20proteins.%20Herein%20we%20present%20a%20single%20cells%20cyclic%20multiplex%20in%20situ%20tagging%20%28CycMIST%29%20technology%20to%20simultaneously%20measure%20%26gt%3B400%20proteins%2C%20a%20scale%20of%20%26gt%3B10%20times%20than%20similar%20technologies.%20Such%20an%20ultra-high%20multiplexity%20is%20achieved%20by%20reiterative%20staining%20of%20the%20single%20cells%20coupled%20with%20a%20MIST%20array%20for%20detection.%20This%20technology%20has%20been%20thoroughly%20validated%20through%20comparison%20with%20flow%20cytometry%20and%20fluorescence%20immunostaining%20techniques.%20Both%20peripheral%20blood%20mononuclear%20cells%20%28PBMCs%29%20and%20T%20cells%20are%20analyzed%20by%20the%20CycMIST%20technology%2C%20and%20almost%20the%20entire%20spectrum%20of%20cluster%20of%20differentiation%20%28CD%29%20surface%20markers%20have%20been%20measured.%20The%20landscape%20of%20fluctuation%20of%20CD%20protein%20expression%20in%20single%20cells%20has%20been%20uncovered%20by%20our%20technology.%20Further%20study%20found%20T%20cell%20activation%20signatures%20and%20the%20protein-protein%20networks.%20This%20study%20represents%20the%20highest%20multiplexity%20of%20single%20immune%20cell%20marker%20measurement%20targeting%20functional%20proteins.%20With%20additional%20information%20from%20intracellular%20proteins%20of%20the%20same%20single%20cells%2C%20our%20technology%20can%20potentially%20facilitate%20mechanistic%20studies%20of%20immune%20responses%20under%20various%20disease%20conditions.%22%2C%22date%22%3A%222024%22%2C%22section%22%3A%22%22%2C%22partNumber%22%3A%22%22%2C%22partTitle%22%3A%22%22%2C%22DOI%22%3A%2210.1021%5C%2Facs.analchem.4c04239%22%2C%22citationKey%22%3A%22%22%2C%22url%22%3A%22https%3A%5C%2F%5C%2Fwww.ncbi.nlm.nih.gov%5C%2Fpmc%5C%2Farticles%5C%2FPMC11648578%5C%2F%22%2C%22PMID%22%3A%2239422499%22%2C%22PMCID%22%3A%22PMC11648578%22%2C%22ISSN%22%3A%220003-2700%22%2C%22language%22%3A%22%22%2C%22collections%22%3A%5B%222RQKSFR5%22%5D%2C%22dateModified%22%3A%222024-12-23T21%3A41%3A57Z%22%7D%7D%2C%7B%22key%22%3A%22RCB4GPF9%22%2C%22library%22%3A%7B%22id%22%3A2323737%7D%2C%22meta%22%3A%7B%22creatorSummary%22%3A%22Flower%20et%20al.%22%2C%22parsedDate%22%3A%222024%22%2C%22numChildren%22%3A1%7D%2C%22bib%22%3A%22%26lt%3Bdiv%20class%3D%26quot%3Bcsl-bib-body%26quot%3B%20style%3D%26quot%3Bline-height%3A%201.35%3B%20padding-left%3A%201em%3B%20text-indent%3A-1em%3B%26quot%3B%26gt%3B%5Cn%20%20%26lt%3Bdiv%20class%3D%26quot%3Bcsl-entry%26quot%3B%26gt%3BFlower%2C%20Cameron%20T.%2C%20Chunmei%20Liu%2C%20Hui-Yu%20Chuang%2C%20Xiaoyang%20Ye%2C%20Hanjun%20Cheng%2C%20James%20R.%20Heath%2C%20Wei%20Wei%2C%20and%20Forest%20M.%20White.%202024.%20%26%23x201C%3BSignaling%20and%20Transcriptional%20Dynamics%20Underlying%20Early%20Adaptation%20to%20Oncogenic%20BRAF%20Inhibition.%26%23x201D%3B%20%26lt%3Bi%26gt%3BbioRxiv%26lt%3B%5C%2Fi%26gt%3B.%20Cold%20Spring%20Harbor%20Laboratory%2C%202024%26%23×2013%3B02.%20%26lt%3Ba%20class%3D%26%23039%3Bzp-ItemURL%26%23039%3B%20href%3D%26%23039%3Bhttps%3A%5C%2F%5C%2Fwww.biorxiv.org%5C%2Fcontent%5C%2F10.1101%5C%2F2024.02.19.581004.abstract%26%23039%3B%26gt%3Bhttps%3A%5C%2F%5C%2Fwww.biorxiv.org%5C%2Fcontent%5C%2F10.1101%5C%2F2024.02.19.581004.abstract%26lt%3B%5C%2Fa%26gt%3B.%20%26lt%3Ba%20title%3D%26%23039%3BCite%20in%20RIS%20Format%26%23039%3B%20class%3D%26%23039%3Bzp-CiteRIS%26%23039%3B%20data-zp-cite%3D%26%23039%3Bapi_user_id%3D2323737%26amp%3Bitem_key%3DRCB4GPF9%26%23039%3B%20href%3D%26%23039%3Bjavascript%3Avoid%280%29%3B%26%23039%3B%26gt%3BCite%26lt%3B%5C%2Fa%26gt%3B%20%26lt%3B%5C%2Fdiv%26gt%3B%5Cn%26lt%3B%5C%2Fdiv%26gt%3B%22%2C%22data%22%3A%7B%22itemType%22%3A%22journalArticle%22%2C%22title%22%3A%22Signaling%20and%20transcriptional%20dynamics%20underlying%20early%20adaptation%20to%20oncogenic%20BRAF%20inhibition%22%2C%22creators%22%3A%5B%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Cameron%20T.%22%2C%22lastName%22%3A%22Flower%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Chunmei%22%2C%22lastName%22%3A%22Liu%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Hui-Yu%22%2C%22lastName%22%3A%22Chuang%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Xiaoyang%22%2C%22lastName%22%3A%22Ye%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Hanjun%22%2C%22lastName%22%3A%22Cheng%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22James%20R.%22%2C%22lastName%22%3A%22Heath%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Wei%22%2C%22lastName%22%3A%22Wei%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Forest%20M.%22%2C%22lastName%22%3A%22White%22%7D%5D%2C%22abstractNote%22%3A%22%22%2C%22date%22%3A%222024%22%2C%22section%22%3A%22%22%2C%22partNumber%22%3A%22%22%2C%22partTitle%22%3A%22%22%2C%22DOI%22%3A%22%22%2C%22citationKey%22%3A%22%22%2C%22url%22%3A%22https%3A%5C%2F%5C%2Fwww.biorxiv.org%5C%2Fcontent%5C%2F10.1101%5C%2F2024.02.19.581004.abstract%22%2C%22PMID%22%3A%22%22%2C%22PMCID%22%3A%22%22%2C%22ISSN%22%3A%22%22%2C%22language%22%3A%22%22%2C%22collections%22%3A%5B%222RQKSFR5%22%5D%2C%22dateModified%22%3A%222025-01-29T00%3A02%3A07Z%22%7D%7D%5D%7D

Su, Yapeng, Chunmei Liu, Xiang Lu, Hui-Yu Chuang, Guideng Li, Shiqun Shao, Yan Kong, et al. 2026. “Sequential Transcriptional Waves and NF-κB-Driven Chromatin Remodeling Direct Drug-Induced Dedifferentiation in Cancer.” Nature Communications 17 (1). Nature Publishing Group: 3228. http://doi.org/10.1038/s41467-026-71349-4. Cite

Wang, Zhuo, Qing Luo, Jie Wu, Li Lu, Wenjie Ding, Yichun Zhao, Yongfeng Yu, et al. 2026. “Spatial Multi-Omics Unveils the Monoclonal Origin, Neuroendocrine Plasticity, and Microenvironment Niches in Combined Small-Cell Lung Cancer.” Cell Reports Medicine 0 (0). Elsevier. http://doi.org/10.1016/j.xcrm.2026.102741. Cite

Wang, Zhuo, Qing Luo, Jie Wu, Wei Wei, Li Lu, Wenjie Ding, Yichun Zhao, et al. 2026. “Spatial Multi-Omics Unveils the Monoclonal Origin, Neuroendocrine Plasticity, and Microenvironment Niches in Combined Small Cell Lung Cancer.” bioRxiv. http://doi.org/10.64898/2026.01.31.702982. Cite

Yan, Xiaowei, Zhuo Wang, Ziming Li, Yichun Zhao, Shun Lu, Qihui Shi, and Wei Wei. 2025. “DTCFinder: A Bench-to-Bits Toolkit for Label-Free, Whole-Spectrum Analysis of Disseminated and Circulating Tumor Cells in Liquid Biopsies.” bioRxiv. http://doi.org/10.1101/2025.11.27.690914. Cite

Flower, Cameron T., Chunmei Liu, Hui-Yu Chuang, Xiaoyang Ye, Hanjun Cheng, James R. Heath, Wei Wei, and Forest M. White. 2025. “Signaling and Transcriptional Dynamics Underlying Early Adaptation to Oncogenic BRAF Inhibition.” Cell Systems, 101239. http://doi.org/10.1016/j.cels.2025.101239. Cite

Kim, Jungwoo, Rachel H. Ng, JingXin Liang, Dazy Johnson, Young Shik Shin, Arion F. Chatziioannou, Michael E. Phelps, Wei Wei, Raphael D. Levine, and James R. Heath. 2024. “Kinetic Trajectories of Glucose Uptake in Single Cancer Cells Reveal a Drug-Induced Cell-State Change Within Hours of Drug Treatment.” The Journal of Physical Chemistry. B. http://doi.org/10.1021/acs.jpcb.4c03663. Cite

Yang, Liwei, Juho Kim, Long Chen, Wei Wei, and Jun Wang. 2024. “Detection of >400 Cluster of Differentiation Biomarkers and Pathway Proteins in Single Immune Cells by Cyclic Multiplex In Situ Tagging for Single-Cell Proteomic Studies.” Analytical Chemistry 96 (43). American Chemical Society: 17387–95. http://doi.org/10.1021/acs.analchem.4c04239. Cite

Yang, Liwei, Juho Kim, Long Chen, Wei Wei, and Jun Wang. 2024. “Detection of >400 CD Biomarkers and Pathway Proteins in Single Immune Cells by Cyclic MIST for Single-Cell Proteomic Studies.” Analytical Chemistry 96 (43): 17387–95. http://doi.org/10.1021/acs.analchem.4c04239. Cite

Flower, Cameron T., Chunmei Liu, Hui-Yu Chuang, Xiaoyang Ye, Hanjun Cheng, James R. Heath, Wei Wei, and Forest M. White. 2024. “Signaling and Transcriptional Dynamics Underlying Early Adaptation to Oncogenic BRAF Inhibition.” bioRxiv. Cold Spring Harbor Laboratory, 2024–02. https://www.biorxiv.org/content/10.1101/2024.02.19.581004.abstract. Cite

Wei Lab
Institute for Systems Biology
401 Terry Ave N
Seattle WA 98109

Email: wei.wei@isbscience.org