Dr. Yaqiang Cao (曹亚强), Ph.D.

System Biology Center, NHLBI, National Institutes of Health (NIH), Bethesda, Maryland, US.

Introduction and Research Overview

I am a Research Fellow at the National Heart, Lung, and Blood Institute (NHLBI) at NIH, specializing in Computational Biology. My work is at the vanguard of epigenomics and 3D genomics, focusing on the intricate chromatin regulatory landscape that governs immunity, leukemia, and aging.

Trained in both bioengineering and computational biology, my research seamlessly integrates cutting-edge computational methods with innovative experimental techniques. I develop robust tools and pioneering protocols—such as high-resolution enhancer-promoter interaction mapping and single-cell nucleosome analysis—to decipher complex biological mechanisms.

My translational approach fosters cross-disciplinary partnerships with biologists, physicians, and data scientists to bridge fundamental science with clinical applications, delivering both mechanistic understanding and user-friendly software for the scientific community.

Academic Journey

2024–Curr.	Research Fellow System Biology Center, NHLBI, NIH, Bethesda, MD, USA. Mentor: Dr. Keji Zhao
2019–2024	Visiting Fellow NHLBI/NIH, Bethesda, MD, USA. Mentor: Dr. Keji Zhao
2012–2018	Ph.D. in Computational Biology Chinese Academy of Sciences (CAS)-Max Planck Society (MPG) Partner Institute for Computational Biology. Mentor: Prof. Jing-Dong Jackie Han
2008–2012	B.S. in Bioengineering East China University of Science and Technology, Shanghai, China.

Technical & Computational Expertise

✓ Epigenomic & 3D Genome Analysis: Expertise in Hi-C, HiChIP, ATAC-seq, ChIP-seq, MNase-seq, Hi-TrAC, RNA-seq, Micro-C, RRBS, EM-seq, and WES.
✓ Single-Cell Technologies: Proficient in 10x single-cell RNA-seq, 10x single-cell multiomics, and scPCOR-seq analysis.
✓ Programming & Software Development: Highly proficient in Python programming and package development (cLoops2, cLoops).
✓ Bioinformatics Infrastructure: Experienced in CPU/GPU server setup and maintenance, and web-application development (astroBoy, glitter).
✓ Machine Learning: Application and development of deep-learning and machine-learning algorithms.

Selected Publications

(* co-first author; # corresponding author) | Full List on Google Scholar

High-Impact First/Co-First Author Papers

Zhen, T. *, Cao, Y. *, et al. (2025). CBFB-SMMHC-driven leukemogenesis requires enhanced RUNX1-DNA binding affinity in mice. J Clin Invest. 10.1172/jci192923. LINK
Ma, F. *, Cao, Y. *, et al. (2024) Three-dimensional chromatin reorganization regulates B cell development during ageing. Nat Cell Biol. 1-12. LINK
Liu, S. *, Cao, Y. *, Cui, K*., et al. (2024) Regulation of T helper cell differentiation by the interplay between histone modification and chromatin interaction. Immunity. 57(5), 987-1004. LINK
Cao, Y. *, Liu, S. *, Cui, K. *, et al. (2023). Hi-TrAC detects active sub-TADs and reveals internal organizations of super-enhancers. Nucleic Acids Research, 51(12), 6172-6189. LINK
Cui, K. *, Chen, Z. *, Cao, Y. *, Liu, S. *, et al. (2023). Restraint of IFN-y expression through a distal silencer CNS-28 for tissue homeostasis. Immunity, 56(5), 944-958. ( Cover Story & Preview). LINK
Cao, Y., Liu, S. *, Ren, G. *, et al. (2022). cLoops2: a full-stack comprehensive analytical tool for chromatin interactions. Nucleic Acids Research, 50(1), 57-71. LINK
Liu, S. *, Cao, Y. *, Cui, K., et al. (2022). Hi-TrAC reveals division of labor of transcription factors in organizing chromatin loops. Nature communications, 13(1), 1-17. LINK
Cao, Y. *, Chen, Z. *, Chen, X. *, Ai, D. *, et al. (2020). Accurate loop calling for 3D genomic data with cLoops. Bioinformatics, 36(3), 666-675. LINK
Zhen, T. *, Cao, Y. *, et al. (2020). RUNX1 and CBFB-SMMHC transactivate target genes together in abnormal myeloid progenitors for leukemia development. Blood, 136(21), 2373-2385. (Plenary Paper). LINK
Han, M. *, Li, J. *, Cao, Y. *, et al. (2020). A role for LSH in facilitating DNA methylation by DNMT1 through enhancing UHRF1 chromatin association. Nucleic Acids Research, 48(21), 12116-12134. LINK
Zeng, Y. *, Cao, Y. *, Halevy, R. S. *, et al. (2020). Characterization of functional transposable element enhancers in acute myeloid leukemia. Science China Life Sciences, 1-13. LINK
Huang, F. *, Cao, Y. *, et al. (2020). BMP2 signaling activation enhances bone metastases of non-small cell lung cancer. Journal of Cellular and Molecular Medicine, 24(18), 10768-10784. LINK
Cao, Y. *, Chen, G. *, Wu, G. *, et al. (2019). Widespread roles of enhancer-like transposable elements in cell identity and long-range genomic interactions. Genome research, 29(1), 40-52. LINK
Wang, L. *, Xu, X. *, Cao, Y. *, et al. (2016). Activin/Smad2-induced H3K27me3 reduction is crucial to initiate mesendoderm differentiation of human embryonic stem cells. Journal of Biological Chemistry, jbc-M116. LINK

Software Development

astroBoy (2022–Curr.): An automated, AI-assisted platform for large-scale NGS data analysis, supporting over 8,000 samples and 370 billion reads. Deployed at NHLBI/NIH.
cLoops2 (2021): A full-stack comprehensive analytical Python package for chromatin interaction data (e.g., Hi-TrAC, HiChIP, Hi-C). Nucleic Acids Research, 2022. GitHub
cLoops (2017): A Python package for accurate and flexible loop calling in 3D genomic data. Bioinformatics, 2020. GitHub
VINCE (2023–Curr.): A de novo Python package for single-cell MNase-seq nucleosome data analysis (Active Development).
Ryder (2025): Python package for epigenome data normalization with internal reference and variable feature detection (Manuscript Submitting).
glitter (2023–Curr.): A custom-built, in-house web application for the analysis and visualization of single-cell RNA-seq data.
TOWN (2019): A Python package for high-throughput, deep learning-augmented bright-field microscopy to automatically count live C. elegans worms.

Contributing Publications (Full List)

Zhu, X., Chen, X., Cao, Y., et al. (2025). Optimal CXCR5 expression during Tfh maturation involves the Bhlhe40-Pou2af1 axis. Cell Reports, 44(11), 116470.
Roy, S., Ren, M., Li, P., Cui, K., Cao, Y., et al. (2025). BLIMP1 negatively regulates IL-2 signaling in T cells. Science Advances, 11(29), eadx8105.
Khateb, M., Jung, R., Leibou, S., Hadley, P., Yu, Z., Dinerman, A. J., Dulemba, V., Gasmi, B., Levin, N., Kim, P., Bhasin, A., Bhat, D., Sindiri, S., Gartner, J. J., Prickett, T. D., Benzine, T., Farid, S. S., Parkhurst, M. R., Halas, H., Cao, Y., et al. (2025). Rapid enrichment of progenitor exhausted neoantigen-specific CD8 T cells from peripheral blood. bioRxiv, 2025-05.
Zhang, X., Jiang, Q., Li, J., Zhang, S., Cao, Y., et al. (2022). KCNQ1OT1 promotes genome-wide transposon repression by guiding RNA–DNA triplexes and HP1 binding. Nature Cell Biology, 1-13.
Lin, X., Liu, Y., Liu, S., Zhu, X., Wu, L., Zhu, Y., Zhao, D., Xu, X., Chemparathy, A., Wang, H., Cao, Y., et al. (2022). Nested epistasis enhancer networks for robust genome regulation. Science, 377(6610), 1077-1085.
Ren, G., Lai, B., Harly, C., Baek, S., Ding, Y., Zheng, M., Cao, Y., et al. (2022). Transcription factors TCF-1 and GATA3 are key factors for the epigenetic priming of early innate lymphoid progenitors toward distinct cell fates. Immunity, 55(8), 1402-1413.
Pan, L., Ku, W. L., Tang, Q., Cao, Y., et al. (2022). scPCOR-seq enables co-profiling of chromatin occupancy and RNAs in single cells. Communications Biology, 5(1), 1-9.
Fang, D., Cui, K., Cao, Y., et al. (2022). Differential regulation of transcription factor T-bet induction during NK cell development and T helper-1 cell differentiation. Immunity, 55(4), 639-655.
Ku, W. L., Pan, L., Cao, Y., et al. (2021). Profiling single-cell histone modifications using indexing chromatin immunocleavage sequencing. Genome Research, 31(10), 1831-1842.
Huang, F., Cao, Y., et al. (2021). PNMA5 promotes bone metastasis of non-small-cell lung cancer as a target of BMP2 signaling. Frontiers in Cell and Developmental Biology, 1400.
Qiu, X., Ma, F., Zhao, M., Cao, Y., et al. (2020). Altered 3D chromatin structure permits inversional recombination at the IgH locus. Science Advances, 6(33), eaaz8850.
Xia, X., Chen, X., Wu, G., Li, F., Wang, Y., Chen, Y., Chen, M., Wang, X., Chen, W., Xian, B., Chen, W., Cao, Y., et al. (2020). Three-dimensional facial-image analysis to predict heterogeneity of the human ageing rate and the impact of lifestyle. Nature Metabolism, 2(9), 946-957.
Chen, X., Xu, C., Hong, S., Xia, X., Cao, Y., et al. (2019). Immune cell types and secreted factors contributing to inflammation-to-cancer transition and immune therapy response. Cell Reports, 26(7), 1965-1977.
Xu, C., Ai, D., Shi, D., Suo, S., Chen, X., Yan, Y., Cao, Y., et al. (2018). Accurate drug repositioning through non-tissue-specific core signatures from cancer transcriptomes. Cell Reports, 25(2), 523-535.
Chen, W., Qian, W., Wu, G., Chen, W., Xian, B., Chen, X., Cao, Y., et al. (2015). Three-dimensional human facial morphologies as robust aging markers. Cell Research, 25(5), 574-587.
Huang, Y., Yu, X., Sun, N., Qiao, N., Cao, Y., et al. (2015). Single-cell-level spatial gene expression in the embryonic neural differentiation niche. Genome Research, 25(4), 570-581.
Hong, S., Huang, Y., Cao, Y., et al. (2014). Approaches to uncovering cancer diagnostic and prognostic molecular signatures. Molecular & Cellular Oncology, 1(2), e957981.

Awards & Honors

2024 NHLBI Director's Award for Innovation
For the discovery of a novel regulatory element for IFN-y expression (Immunity, 2023).

Professional Service

Editorial Board: Frontiers in Immunology Frontiers in Medicine.
Peer Reviewer for Prestigious Journals: Nature Communications, Bioinformatics, Communications Biology, BMC Genomics, BMC Bioinformatics, Frontiers in Immunology, Genes, Cells, etc..