Vision statement:

Our research group focuses on developing and applying cutting-edge, spatially resolved, high-throughput single-cell DNA and multi-omics sequencing technologies (genome/transcriptome/epigenomics/proteomics et.al) to map and characterize disease initiating cells, treatment resistant cells in human disease and cancer. By integrating somatic mutations, copy number alterations, gene expression, chromatin accessibility, DNA methylation, proteomic and other measurements from the same single cells and their surrounding microenvironment, we’re aiming to pinpoint the key driver events that initiate and propel disease and tumor progression.

Beyond cancer biology, our team is deeply interested in combining the unique single-cell multi-omics datasets we generate with advanced artificial intelligence (AI) approaches to create “digital cells” and decipher the fundamental principles of cellular behavior. Ultimately, we aspire to build AI models capable of predicting cellular states and behaviors from limited molecular information, with the long-term vision of transforming our ability to diagnose, treat, and cure cancer and other diseases.

Previous research accomplishment:

Our research has centered on developing transformative high-throughput single-cell multi-omics sequencing and spatial sequencing technologies to decode the earliest events in human breast cancer. These technologies have enabled direct linkage of copy number alterations, gene expression programs, and chromatin states within individual cells, providing unprecedented insights into tumor-initiating cell populations, clonal persistence, and microenvironmental reprogramming.

   

#: corresponding author; * first author

1. Wang K ^# *, Ye R*, Bai S, Xiao Z, Yang L, Li J, Tang C, Sei E, Peng J, Casasent AK, Lin SH, Nagi C, Thompson AM, Krishnamurthy S, Navin N^#. Coalescing single-cell genomes and transcriptomes to decode breast cancer progression. Cell. 2025 Oct 30;188(22):6355-6369.e16. doi: 10.1016/j.cell.2025.08.012. PMID: 40912251

2. 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 genomics reveals persistent subclones during DCIS progression. Cell. 2023 Aug 31;186(18):3968-3982.e15. doi: 10.1016/j.cell.2023.07.024. Epub 2023 Aug 15. PMID: 37586362 

3. Wang K*, Yan Y*, Elgamal H*, Li J, Tang C, Bai S, Xiao Z, Sei E, Lin Y, Wang J, Montalvan J, Nagi C, Thompson AM, Navin N#. Single cell genome and epigenome co-profiling reveals hardwiring and plasticity in breast cancer. bioRxiv. 2024 Sep 10:2024.09.06.611519. doi: 10.1101/2024.09.06.611519. PMID: 39314325

4. Wang K*, Xiao Z*, Yan Y*, Ye R, Hu M, Bai S, Sei E, Qiao Y, Chen H, Lim B, Lin S, Navin N^#. Simple oligonucleotide-based multiplexing of single-cell chromatin accessibility. Molecular Cell. 2021 Oct 21;81(20):4319-4332.e10. doi: 10.1016/j.molcel.2021.09.026. PMID: 34686316 

5. Wang K^#. Revealing genomic secrets of archival FFPE samples. Nature Reviews Cancer. 2024 Jun;24(6):359. doi: 10.1038/s41568-024-00686-7. PMID: 38589556

6. Wang K, Lai S, Yang X, Zhu T, Lu X, Wu CI^#, Ruan J^#. Ultrasensitive and high-efficiency screen of de novo low-frequency mutations by o2n-seq.  Nature communications. 2017 May 22;8:15335. doi: 10.1038/ncomms15335. PMID: 28530222

1. Nicholas Navin, Kaile Wang, Rui Ye. Methods for simultaneous amplification of DNA and RNA. PCT/US2023/074051; filed.

2. Kaile Wang, Nicholas Navin, Yun Yan, Heba Elgamal, Yiyun Lin, and Junke Wang.  Methods and compositions for amplification and sequencing of genome and epigenome. PCT/US2024/018634; filed.

3. Nicholas Navin, Kaile Wang. Methods and applications for cell barcoding. United States, UTSC.P1153US.P1, 4/1/2019, filed.

4. Jue Ruan, Kaile Wang. Next-generation sequencing library preparation and application. International, WO2017054302A1, issued.

5. Jue Ruan, Kaile Wang, Xu Shen, Xuemei Lu, Chung-I Wu. A DNA amplification method. China. CN105463066A, 9/4/2014, issued.

6. Kaile Wang, Jue Ruan, Xuemei Lu, Chung-I Wu. Improved Next-generation Library preparation and application. China, CN105420348A, 9/4/2014, issued.

7. Zuyu Yang, Kaile Wang, Dafei Wu, Xuemei lu, Chung-I Wu. Trace DNA-based next-generation sequencing library construction method. China, CN103938277A, 04/18/2014. issued.

8. Jue Ruan, Kaile Wang, Xuemei Lu, Chung-I Wu. Next-generation Library preparation and application. International, WO2015081890A1, 12/06/2013, issued.

* Development of single cell multi-omics and spatial genomics technologies.

* Tumor origin, progression, recurrence and therapeutic resistance.

* Somatic mosaicism during aging.

* AI modeling and single cell digitization.

1. “Simultaneously single cell genome and transcriptome sequencing uncovers the origin and evolution of cancer”, The 4th International Conference on Single-cell and Spatial Omics. China, Shanghai. Mar 28-29, 2026.

2. “Single-Cell DNA and Multi-Omics Sequencing to Investigate Breast Cancer Initiation and Recurrence”, 2025 Frontiers in Life Omics Technologies and Translational Conference. China, Jiangsu. Nov 11-13, 2025.

3. “High-throughput scDNA and multiomics sequencing reveal the origin and recurrence of breast cancer”, The 3rd International Conference on Single-cell and Spatial Omics. China, Shanghai. Mar 29-31, 2025.

4. “Detection of rare, yet crucial tumor subclones”, Shanghai Bioinformatics Society 2024 Annual Conference. China, Shanghai. Oct 19-20, 2024.

5. “High throughput scDNA-seq of FFPE tissues reveals persistent subclones over years to decades of DCIS progression”, Gordon Research Conference (Single-Cell Cancer Biology). Boston, US. June12-17, 2022.

6. “Multiplexing scATAC and scATAC&RNA Sequencing With Unmodified Oligonucleotides” CSHL (Cold Spring Harbor Laboratory Conference), single cell analyses (Virtual). Houston, US. Nov 11, 2021.

7. “Single nucleus sequencing identifies spatial reprogramming of the microenvironment in premalignant breast cancer”, 21th Advances genome biology technology (AGBT). Houston, US (virtual). Mar 2, 2021.