探究肿瘤细胞的起源及演化对理解癌症的发生、复发以及对后续肿瘤的预防和治疗至关重要。肿瘤细胞起源于正常细胞内突变的积累，然后在微环境、手术、放化疗等不同的选择压力下，经历多个阶段的演化。对演化过程的研究能够揭示癌症的发生、发展规律，鉴定癌细胞起源及演化相关的基因组事件，进而为治疗肿瘤提供新的药物靶点。研究组前期通过开发高通量单细胞DNA测序技术（Arc-well）、单细胞进行空间位置（或样本信息）标记的方法SNuBar以及多种基于高通量测序的低频突变检测方法（o2n-seq, Droplet-CirSeq, Oseq和EasyMF）系统研究了乳腺癌原发到复发的克隆演化关系，揭示了原发到复发癌的克隆演化模型，鉴定了与乳腺癌复发相关的基因组变异事件，为后续乳腺癌的治疗提供了目标靶点。课题组将继续通过开发高通量单细胞多组学测序技术、空间组学测序技术等来回答关于肿瘤细胞起源和演化的问题：如体细胞突变如何导致肿瘤的发生，导致肿瘤起源的上皮细胞亚型，肿瘤起始细胞空间定位、多组学表征及其与微环境互作关系，衰老与肿瘤的关系等。

1. Wang K*, Kumar T*, Wang J, Minussi, D, Sei E, Li J, Tran T, Thennavan A, Hu M, Casasent A, Xiao Z, Bai S, King L, Shah V, Kristel P, Borden C, Marks J, Zhao Y, Zurita A, Aparicio A, Chapin B, Ye J, Zhang J, Gibbons D, Grand Challenge PRECISION Consortium, Sawyer E, Thompson A, Futreal A, Hwang ES, Wesseling J, Lips E, Navin N#. Archival single cell genome sequencing reveals persistent subclones over years to decades of DCIS progression. Cell. 2023; 186(18):3968-3982.e15. doi: 10.1016/j.cell.2023.07.024
2. Wang K^#. Revealing genomic secrets of archival FFPE samples. Nature Reviews Cancer. 2024. https://doi.org/10.1038/s41568-024-00686-7.
3. Wang K*, Xiao Z*, Yan Y*, Ye R, Hu M, Bai S, Sei E, Qiao Y, Chen H, Lim B, Lin S, Navin N#. Highly-multiplexed sample and spatial barcoding of single cell chromatin accessibility using a single oligonucleotide. Molecular Cell. 2021; 81, 4319-4332: doi:10.1016/j.molcel.2021.09.026.
4. Wang K, Lai S, Chang Y, Lu X, Wu C#, Ruan J#. Ultra-precisely and low bias screen low frequency mutations by o2n-seq. Nature communications. 2017; 8:15335: doi: 10.1038/ncomms15335.
5. Wang K*, Ma X*, Zhang X, Wu D, Sun C, Sun Y, Lu X, Wu C#, Guo C#, Ruan J#. Using ultra-sensitive next generation sequencing to dissect DNA damage-induced mutagenesis. Scientific Reports. 2016; 6:25310: doi: 10.1038/srep25310.
6. Wang K, Ma Q, Jiang L, Lai S, Lu X, Hou Y#, Wu C#, Ruan J#. Ultra-precise detection of mutations by droplet-based amplification of circularized DNA. BMC Genomics. 2016; 17:214: doi: 10.1186/s12864-016-2480-1.
7. Minussi D*, Nicholson M*, Ye H*, Davis A, Wang K, Baker T, Sei E, Du H, Rabbani M, Peng C, Hu M, Bai S, Lin Y, Schalck A, Multani A, Ma J, McDonald T, Tarabichi M, Casasent A, Barrera A, Chen H, Lim B, Arun B, Meric-Bernstam F, Loo P, Michor F#, Navin N#. Breast Tumors Maintain a Reservoir of Subclonal Diversity During Primary Expansion. Nature. 2021: doi: 10.1038/s41586-021-03357-x.
8. Yu L*#, Wang G*, Ruan J*, Chen Y*, Yang C*, Cao X*, Wu H*, Liu Y*, Du Z*, Wang X*, Yang J*, Cheng S*, Zhong L, Wang L, Wang X, Hu J, Fang L, Bai B, Wang K, Yuan N, Wu S, Li B, Zhang J, Yang Y, Zhang C, Long Y, Li H, Yang J, Irwin D, Ryder O, Li Y, Wu C#, Zhang Y#. Genomic analysis of snub-nosed monkeys (Rhinopithecus) identifies genes and processes related to high-altitude adaptation. Nature Genetics. 2016; 48, 947–952: doi: 10.1038/ng.3615.