Dr. Yaqiang Cao (曹亚强), Ph.D.

Systems Biology Center, NHLBI, National Institutes of Health (NIH), Bethesda, Maryland, USA.

Introduction and Research Overview

I am a Research Fellow at the National Heart, Lung, and Blood Institute (NHLBI), NIH. My research in computational biology focuses on chromatin regulation in immunity, leukemia, and aging.

I develop computational and experimental methods for high-resolution enhancer–promoter and single-cell nucleosome mapping. My work examines how chromatin loops, histone modifications, and transcription factors shape T-cell differentiation, acute myeloid leukemia, and B-cell aging.

Through collaborations with biologists, physicians, and data scientists, I connect basic research with clinical applications and develop user-friendly software for epigenomic and 3D genome research.

Academic Journey

2024–Present	Research Fellow Systems Biology Center, NHLBI, NIH, Bethesda, MD, USA. Mentor: Dr. Keji Zhao
2019–2024	Visiting Fellow NHLBI/NIH, Bethesda, MD, USA. Mentor: Dr. Keji Zhao
2019	Ph.D. in Computational Biology Chinese Academy of Sciences (CAS)–Max Planck Society (MPG) Partner Institute for Computational Biology, University of Chinese Academy of Sciences (UCAS), Shanghai, China. Mentor: Prof. Jing-Dong Jackie Han
2011–2018	Graduate Research Assistant CAS–MPG Partner Institute for Computational Biology, Shanghai, China. Mentor: Prof. Jing-Dong Jackie Han
2012	B.S. in Bioengineering East China University of Science and Technology, Shanghai, China.

Technical & Computational Expertise

✓ Epigenomic & 3D Genome Analysis: Hi-C, HiChIP, Micro-C, Hi-TrAC, ATAC-seq, ChIP-seq, MNase-seq, STARR-seq, RRBS, EM-seq, and whole-exome sequencing (WES); custom computational methods and complex data mining.
✓ Transcriptomics & Single-Cell Multiomics: RNA-seq, 10x single-cell RNA-seq, and integrated 10x ATAC + gene expression analysis.
✓ Programming & Software Development: Python programming and package development, including Ryder, cLoops2, cLoops, and cLoops3 (in development).
✓ Bioinformatics Infrastructure: CPU/GPU server setup and maintenance; web application development, including astroBoy and glitter.
✓ Machine Learning: Application and development of deep learning and machine learning algorithms.

Publications

34 journal articles and 2 preprints; 16 first- or co-first-author articles.
^* Equal contribution; ^# Corresponding author. | Google Scholar

First- and Co-First-Author Publications

Cao, Y.^*, Ge, G.^*, & Zhao, K.^# (2026). Ryder: Epigenome normalization using a two-tier model and internal reference regions. Bioinformatics, btag753. Advance online publication. https://doi.org/10.1093/bioinformatics/btag753
Cao, Y., Tang, Q., & Zhao, K.^# (2026). Elucidation of chromatin loops among regulatory regions using Hi-TrAC. Frontiers in Epigenetics and Epigenomics, 4, 1858923. https://doi.org/10.3389/freae.2026.1858923
Zhen, T.^*, Cao, Y.^*, Dou, T., Chen, Y., Lopez, G., Menezes, A. C., Wu, X., Hammer, J. A., Cheng, J., Garrett, L., Anderson, S., Kirby, M., Wincovitch, S., Sisay, B., Elkahloun, A. G., Wu, D., Castilla, L. H., Yang, W., Jiang, J., Zhao, K., & Liu, P. P.^# (2025). CBFβ-SMMHC–driven leukemogenesis requires enhanced RUNX1-DNA binding affinity in mice. The Journal of Clinical Investigation, 135(19), e192923. https://doi.org/10.1172/JCI192923
Ma, F.^*, Cao, Y.^*, Du, H., Braikia, F. Z., Zong, L., Ollikainen, N., Bayer, M., Qiu, X., Park, B., Roy, R., Nandi, S., Sarantopoulou, D., Ziman, A., Bianchi, A. H., Beerman, I., Zhao, K., Grosschedl, R., & Sen, R.^# (2024). Three-dimensional chromatin reorganization regulates B cell development during ageing. Nature Cell Biology, 26(6), 991–1002. https://doi.org/10.1038/s41556-024-01424-9
Liu, S.^*, Cao, Y.^*, Cui, K.^*, Ren, G., Zhao, T., Wang, X., Wei, D., Chen, Z., Gurram, R. K., Liu, C., Wu, C., Zhu, J., & Zhao, K.^# (2024). Regulation of T helper cell differentiation by the interplay between histone modification and chromatin interaction. Immunity, 57(5), 987–1004.e5. https://doi.org/10.1016/j.immuni.2024.03.018
Cao, Y.^*, Liu, S.^*, Cui, K.^*, Tang, Q., & Zhao, K.^# (2023). Hi-TrAC detects active sub-TADs and reveals internal organizations of super-enhancers. Nucleic Acids Research, 51(12), 6172–6189. https://doi.org/10.1093/nar/gkad378
Cui, K.^*, Chen, Z.^*, Cao, Y.^*, Liu, S.^*, Ren, G., Hu, G., Fang, D., Wei, D., Liu, C., Zhu, J., Wu, C.^#, & Zhao, K.^# (2023). Restraint of IFN-γ expression through a distal silencer CNS–28 for tissue homeostasis. Immunity, 56(5), 944–958.e6. (Cover article; highlighted in an Immunity Preview.) https://doi.org/10.1016/j.immuni.2023.03.006
Cao, Y.^*, Liu, S.^*, Ren, G.^*, Tang, Q., & Zhao, K.^# (2022). cLoops2: a full-stack comprehensive analytical tool for chromatin interactions. Nucleic Acids Research, 50(1), 57–71. https://doi.org/10.1093/nar/gkab1233
Liu, S.^*, Cao, Y.^*, Cui, K., Tang, Q., & Zhao, K.^# (2022). Hi-TrAC reveals division of labor of transcription factors in organizing chromatin loops. Nature Communications, 13(1), 6679. https://doi.org/10.1038/s41467-022-34276-8
Cao, Y.^*, Chen, Z.^*, Chen, X.^*, Ai, D.^*, Chen, G., McDermott, J., Huang, Y., Guo, X., & Han, J.-D. J.^# (2020). Accurate loop calling for 3D genomic data with cLoops. Bioinformatics, 36(3), 666–675. https://doi.org/10.1093/bioinformatics/btz651
Zhen, T.^*, Cao, Y.^*, Ren, G., Zhao, L., Hyde, R. K., Lopez, G., Feng, D., Alemu, L., Zhao, K., & Liu, P. P.^# (2020). RUNX1 and CBFβ-SMMHC transactivate target genes together in abnormal myeloid progenitors for leukemia development. Blood, 136(21), 2373–2385. (Plenary Paper.) https://doi.org/10.1182/blood.2020007747
Han, M.^*, Li, J.^*, Cao, Y.^*, Huang, Y., Li, W., Zhu, H., Zhao, Q., Han, J.-D. J., Wu, Q., Li, J., Feng, J.^#, & Wong, J.^# (2020). A role for LSH in facilitating DNA methylation by DNMT1 through enhancing UHRF1 chromatin association. Nucleic Acids Research, 48(21), 12116–12134. https://doi.org/10.1093/nar/gkaa1003
Zeng, Y.^*, Cao, Y.^*, Halevy, R. S.^*, Nguyen, P., Liu, D., Zhang, X., Ahituv, N.^#, & Han, J.-D. J.^# (2020). Characterization of functional transposable element enhancers in acute myeloid leukemia. Science China Life Sciences, 63(5), 675–687. https://doi.org/10.1007/s11427-019-1574-x
Huang, F.^*#, Cao, Y.^*, Wu, G., Chen, J., Wang, C., Lin, W., Lan, R., Wu, B., Xie, X., Hong, J., & Fu, L. (2020). BMP2 signalling activation enhances bone metastases of non-small cell lung cancer. Journal of Cellular and Molecular Medicine, 24(18), 10768–10784. https://doi.org/10.1111/jcmm.15702
Cao, Y.^*, Chen, G.^*, Wu, G.^*, Zhang, X.^*, McDermott, J., Chen, X., Xu, C., Jiang, Q., Chen, Z., Zeng, Y., Ai, D., Huang, Y., & Han, J.-D. J.^# (2019). Widespread roles of enhancer-like transposable elements in cell identity and long-range genomic interactions. Genome Research, 29(1), 40–52. https://doi.org/10.1101/gr.235747.118
Wang, L.^*, Xu, X.^*, Cao, Y.^*, Li, Z., Cheng, H., Zhu, G., Duan, F., Na, J., Han, J.-D. J., & Chen, Y.-G.^# (2017). Activin/Smad2-induced histone H3 Lys-27 trimethylation (H3K27me3) reduction is crucial to initiate mesendoderm differentiation of human embryonic stem cells. Journal of Biological Chemistry, 292(4), 1339–1350. https://doi.org/10.1074/jbc.M116.766949

Software Development

astroBoy (2022–Present): An automated, AI-assisted next-generation sequencing analysis platform for in-house and public datasets on a single-node server. Deployed at NHLBI/NIH; processed over 530 billion reads from more than 10,000 samples across 900 analysis jobs since December 2022.
glitter (2023–Present): An in-house web application for analyzing and visualizing single-cell RNA-seq data to support collaborative research.
VINCE (2023–Present): A Python package for nucleosome analysis using single-cell MNase-seq data, currently under active development and optimization. GitHub
cLoops3 (2026–Present): Chromatin interaction analysis software under development since 2026, with assistance from Codex for code enhancements.
Ryder (2026): A Python package for epigenomic normalization using internal reference regions and variable-feature detection. Accepted and published in Bioinformatics (2026). GitHub Paper
cLoops2 (2021): A Python package for comprehensive analysis of chromatin interaction data, including Hi-TrAC, HiChIP, and Hi-C (Nucleic Acids Research, 2022). GitHub
TOWN (2019): A Keras-based Python package for automated counting of live C. elegans in high-throughput bright-field microscopy images using deep learning. Developed for in-house drug screening to identify compounds that improve worm survival.
cLoops (2017): A Python package for accurate and flexible loop calling from 3D genomic data (Bioinformatics, 2020). GitHub

Additional Journal Articles

Khateb, M., Jung, R., Hadley, P., Leibou, S., Yu, Z., Dinerman, A. J., Dulemba, V., Gasmi, B., Levin, N., Kim, S. P., Bhasin, A., Bhat, D., Sindiri, S., Gartner, J. J., Prickett, T. D., Benzine, T., Farid, S., Parkhurst, M., Halas, H., Ge, G., Cao, Y., Zhao, K., Yang, J. C., Robbins, P., Lowery, F. J., Krishna, S., Heller, T., McVicar, D., Rosenberg, S. A., & Klemen, N. D. (2026). Selective expansion of neoantigen-specific peripheral blood lymphocytes through antigen-presenting cell-T cell conjugate isolation. Journal for ImmunoTherapy of Cancer, 14(10), e014996. https://doi.org/10.1136/jitc-2026-014996
Zong, L., Park, B., Cao, Y., Ma, F., Tekin-Turhan, F., Kuribayashi, W., Zhao, K., & Beerman, I. (2026). Chromatin reorganization drives overexpression of a Btaf1 variant underpinning hematopoietic aging. Nature Communications, 17(1), 4129. https://doi.org/10.1038/s41467-026-70787-4
Zhu, X., Chen, X., Cao, Y., Liu, C., Kline, Z. J., Hu, G., Ganesan, S., Veres, T. Z., Fang, D., Liu, S., Wei, D., Shibata, H., Golec, D. P., Chung, H., Germain, R. N., Schwartzberg, P. L., Zhao, K., & Zhu, J. (2025). Optimal CXCR5 expression during Tfh maturation involves the Bhlhe40-Pou2af1 axis. Cell Reports, 44(11), 116470. https://doi.org/10.1016/j.celrep.2025.116470
Roy, S., Ren, M., Li, P., Cui, K., Cao, Y., Fisk, B., Markowitz, T. E., Redekar, N., Sakamoto, K., Nagao, K., Oh, J., Spolski, R., Liao, W., Dubois, S. P., Kelsall, B. L., Zhao, K., Phelan, J. D., & Leonard, W. J. (2025). BLIMP1 negatively regulates IL-2 signaling in T cells. Science Advances, 11(29), eadx8105. https://doi.org/10.1126/sciadv.adx8105
Zhang, X., Jiang, Q., Li, J., Zhang, S., Cao, Y., Xia, X., Cai, D., Tan, J., Chen, J., & Han, J.-D. J. (2022). KCNQ1OT1 promotes genome-wide transposon repression by guiding RNA–DNA triplexes and HP1 binding. Nature Cell Biology, 24(11), 1617–1629. https://doi.org/10.1038/s41556-022-01008-5
Lin, X., Liu, Y., Liu, S., Zhu, X., Wu, L., Zhu, Y., Zhao, D., Xu, X., Chemparathy, A., Wang, H., Cao, Y., Nakamura, M., Noordermeer, J. N., La Russa, M., Wong, W. H., Zhao, K., & Qi, L. S. (2022). Nested epistasis enhancer networks for robust genome regulation. Science, 377(6610), 1077–1085. https://doi.org/10.1126/science.abk3512
Ren, G., Lai, B., Harly, C., Baek, S., Ding, Y., Zheng, M., Cao, Y., Cui, K., Yang, Y., Zhu, J., Hager, G. L., Bhandoola, A., & Zhao, K. (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.e4. https://doi.org/10.1016/j.immuni.2022.06.019
Pan, L., Ku, W. L., Tang, Q., Cao, Y., & Zhao, K. (2022). scPCOR-seq enables co-profiling of chromatin occupancy and RNAs in single cells. Communications Biology, 5(1), 678. https://doi.org/10.1038/s42003-022-03584-6
Fang, D., Cui, K., Cao, Y., Zheng, M., Kawabe, T., Hu, G., Khillan, J. S., Li, D., Zhong, C., Jankovic, D., Sher, A., Zhao, K., & Zhu, J. (2022). Differential regulation of transcription factor T-bet induction during NK cell development and T helper-1 cell differentiation. Immunity, 55(4), 639–655.e7. https://doi.org/10.1016/j.immuni.2022.03.005
Ku, W. L., Pan, L., Cao, Y., Gao, W., & Zhao, K. (2021). Profiling single-cell histone modifications using indexing chromatin immunocleavage sequencing. Genome Research, 31(10), 1831–1842. https://doi.org/10.1101/gr.260893.120
Huang, F., Cao, Y., Wang, C., Lan, R., Wu, B., Xie, X., Hong, J., Fu, L., & Wu, G. (2021). PNMA5 promotes bone metastasis of non-small-cell lung cancer as a target of BMP2 signaling. Frontiers in Cell and Developmental Biology, 9, 678931. https://doi.org/10.3389/fcell.2021.678931
Qiu, X., Ma, F., Zhao, M., Cao, Y., Shipp, L., Liu, A., Dutta, A., Singh, A., Braikia, F. Z., De, S., Wood, W. H., III, Becker, K. G., Zhou, W., Ji, H., Zhao, K., Atchison, M. L., & Sen, R. (2020). Altered 3D chromatin structure permits inversional recombination at the IgH locus. Science Advances, 6(33), eaaz8850. https://doi.org/10.1126/sciadv.aaz8850
Xia, X., Chen, X., Wu, G., Li, F., Wang, Y., Chen, Y., Chen, M., Wang, X., Chen, W., Xian, B., Chen, W., Cao, Y., Xu, C., Gong, W., Chen, G., Cai, D., Wei, W., Yan, Y., Liu, K., Qiao, N., Zhao, X., Jia, J., Wang, W., Kennedy, B. K., Zhang, K., Cannistraci, C. V., Zhou, Y., & Han, J.-D. J. (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. https://doi.org/10.1038/s42255-020-00270-x
Chen, X., Xu, C., Hong, S., Xia, X., Cao, Y., McDermott, J., Mu, Y., & Han, J.-D. J. (2019). Immune cell types and secreted factors contributing to inflammation-to-cancer transition and immune therapy response. Cell Reports, 26(7), 1965–1977.e4. https://doi.org/10.1016/j.celrep.2019.01.080
Xu, C., Ai, D., Shi, D., Suo, S., Chen, X., Yan, Y., Cao, Y., Zhang, R., Sun, N., Chen, W., McDermott, J., Zhang, S., Zeng, Y., & Han, J.-D. J. (2018). Accurate drug repositioning through non-tissue-specific core signatures from cancer transcriptomes. Cell Reports, 25(2), 523–535.e5. https://doi.org/10.1016/j.celrep.2018.09.031
Chen, W., Qian, W., Wu, G., Chen, W., Xian, B., Chen, X., Cao, Y., Green, C. D., Zhao, F., Tang, K., & Han, J.-D. J. (2015). Three-dimensional human facial morphologies as robust aging markers. Cell Research, 25(5), 574–587. https://doi.org/10.1038/cr.2015.36
Huang, Y., Yu, X., Sun, N., Qiao, N., Cao, Y., Boyd-Kirkup, J. D., Shen, Q., & Han, J.-D. J. (2015). Single-cell-level spatial gene expression in the embryonic neural differentiation niche. Genome Research, 25(4), 570–581. https://doi.org/10.1101/gr.181966.114
Hong, S., Huang, Y., Cao, Y., Chen, X., & Han, J.-D. J. (2014). Approaches to uncovering cancer diagnostic and prognostic molecular signatures. Molecular & Cellular Oncology, 1(2), e957981. https://doi.org/10.4161/23723548.2014.957981

Preprints

Zhu, X., Song, J., Nie, J., Chen, X., Cao, Y., Wei, D., Gurram, R. K., Peng, D., Zhao, K., Bosselut, R., & Zhu, J. (2026). The transcription factor Bhlhe40 promotes inflammatory functions of ILC2s through inducing GM-CSF while inhibiting IL-10 expression. bioRxiv [Preprint]. https://doi.org/10.64898/2026.08.23.746557
Liu, N., Xu, J., Ku, W. L., Chen, W., Cao, Y., Kazmi, R., Jin, W., Gauthier, T., Luo, S., Shen, S., Patimo Molano, L., Lim, Y.-J., Ottaviani, V., Naylor, E., Zhao, K., & Chen, W. (2026). Destabilization of intratumor Tregs by CTLA-4 engagement confers anti-CTLA-4-driven immunotherapy. bioRxiv [Preprint]. https://doi.org/10.64898/2026.07.28.741328

Awards & Honors

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

Professional Service

Editorial Board: Frontiers in Immunology; Frontiers in Medicine; Frontiers in Epigenetics and Epigenomics.
Journal Peer Review: Nature Communications; Genome Biology; Bioinformatics; Communications Biology; BMC Bioinformatics; BMC Genomics; F1000Research; Frontiers in Immunology; Frontiers in Bioinformatics; Genes; Cells.