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About Me

As a physician–scientist at the crossroads of immuno-oncology and computational biology, my research seeks to define the next generation of precision immunotherapies. I combine AI-driven multi-omics, single-cell, and spatial technologies with experimental models to uncover how cancer cells evade both standard-of-care and experimental treatments.

My work has revealed novel biomarkers and therapeutic targets in bladder and other solid tumors, leading to the discovery of loss of the Y chromosome (LOY) as a fundamental, pan-cancer mechanism of immune escape. As co-first author (Nature, 2023), my team showed that LOY in cancer cells promotes immune evasion and tumor aggressiveness. As first author (Nature, 2025), I demonstrated that LOY in patients’ T cells disrupts anti-tumor immunity, creating a “two-hit” mechanism that accelerates disease progression. These findings uncover new therapeutic vulnerabilities and inform the design of next-generation cellular immunotherapies.

Looking ahead, my laboratory will pioneer the use of genomic large language models (LLMs) and DNA sequence-to-function architectures for in silico functional genomics. By integrating predictive AI with high-resolution single-cell and spatial profiling, we aim to: (1) develop novel therapies to reverse LOY-driven immune escape, and (2) build AI-powered biomarkers for early cancer detection and therapeutic response prediction.

Grounded in clinical oncology and computational science, my vision is to bridge computational discovery with patient impact—transforming how we understand, detect, and treat cancer.

Research Interests

  • Bioinformatics and Computational Biology
  • Large Language Models & Foundation AI for Genomics
  • Single-Cell & Spatial Multi-Omics Integration
  • AI-Powered Predictive Modeling, Radiogenomics & Digital Pathology
  • Cancer Immunotherapy & Tumor Microenvironment Systems Biology

Research Projects

(1) The Role of Y-Chromosome Loss in Immune Modulation and Tumorigenesis

Selected Publications
Concurrent loss of the Y chromosome in cancer and T cells impacts outcome

Chen, X., Shen, Y., Choi, S. et al. Nature 642, 1041–1050 (2025). First author. https://doi.org/10.1038/s41586-025-09071-2 a>

In our 2025 Nature study (first authored by me), we demonstrated that age-related loss of the Y chromosome (LOY)—which affects up to 40% of elderly men—occurs not only in tumour cells but also spreads to infiltrating T cells; this “double-LOY” condition cripples anti-tumour immunity and predicts the worst survival across 4,000 male cancer samples and more than one million single-cell profiles. Mechanistically, losing key Y-linked genes (KDM5D, UTY, DDX3Y) weakens tumour antigen presentation, while LOY T cells become exhausted (↓ GZMB/PRF1, ↑ PD-1/CTLA-4), offering an explanation for men’s higher cancer burden. These findings argue for routine LOY testing in male-predominant cancers, careful exclusion of LOY T cells from cell therapies, and development of treatments that restore or block LOY-driven immune collapse.

Nature News & Views (4 June 2025) spotlighted our Nature paper revealing Y-chromosome loss (LOY) in both tumour cells and infiltrating T cells. Commentators Nicholas McGranahan (University College London) and Rahul Roychoudhuri (University of Cambridge) contend that this coordinated LOY weakens antitumour immunity, enables escape, and predicts poorer survival. They urge clinicians to assess LOY in both compartments for prognosis, use Y-status to guide immuno- and cell-therapy choices, and investigate how Y-deficient tumours trigger LOY in nearby immune cells to discover new therapeutic targets.

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Nature Journal Headline
Y chromosome loss in cancer drives growth by evasion of adaptive immunity

Abdel-Hafiz, H.A., Schafer, J.M., Chen, X. et al. Nature 619, 624-631 (2023). Co-first author. https://doi.org/10.1038/s41586-023-06234-x a>

Our 2023 Nature paper (co-first authored by me) delivered the first direct evidence that loss of the Y chromosome (LOY) in cancer cells reshapes anti-tumor immunity. Using mouse models and large human cohorts of bladder cancer, we showed that Y-negative tumors up-regulate PD-L1, drive T-cell exhaustion, and proliferate twice as fast as Y-positive tumors. Paradoxically, the same immune-evasive state renders LOY tumors markedly more responsive to immune-checkpoint blockade (e.g., atezolizumab). These findings uncover a causal link between sex-chromosome loss and immune escape, offer a mechanistic explanation for the higher incidence and poorer prognosis of many cancers in men, and position LOY as a predictive biomarker for immunotherapy benefit.

(2) Multi-Omics Biomarker Toolkit Driving Precision Oncology in Urologic Cancers

My biomarker work spans several studies that converge on three advances: (1) AI-powered radiogenomics that pairs MRI with RNA-seq to stage muscle-invasive bladder cancer more accurately than imaging alone; (2) multi-omics immune signatures—covering pyroptosis, hypoxia, autophagy, ferroptosis, m6A and CD8-T-effector checkpoints—that stratify patients and predict checkpoint-inhibitor benefit across bladder, ovarian and other cancers; and (3) mechanistic discoveries (e.g., KDM5D/UTY loss, SRSF10-CDC25A splicing, lncRNA FOXD1-AS1) that reveal druggable pathways driving tumour metabolism and immune escape, together forming a toolkit for precision oncology.

  1. Qureshi TA*, Chen X*, Xie Y, Murakami K, Sakatani T, Kita Y, Kobayashi T, Miyake M, Knott SRV, Li D et al: MRI/RNA-Seq-Based Radiogenomics and Artificial Intelligence for More Accurate Staging of Muscle-Invasive Bladder Cancer. Int J Mol Sci 2023, 25(1). (Co-first author)
  2. Chen X, Xu R, He D, Zhang Y, Chen H, Zhu Y, Cheng Y, Liu R, Zhu R, Gong L et al: CD8(+) T effector and immune checkpoint signatures predict prognosis and responsiveness to immunotherapy in bladder cancer. Oncogene 2021, 40(43):6223-6234. (First author)
  3. Chen X*, Chen H*, Yao H, Zhao K, Zhang Y, He D, Zhu Y, Cheng Y, Liu R, Zhu R, Gong L et al: Turning up the heat on non-immunoreactive tumors: pyroptosis influences the tumor immune microenvironment in bladder cancer. Oncogene 2021, 40(45):6381-6393. (Co-first author)
  4. Chen X*, Lan H*, He D, Zhu Y, Xiao M, Lan H, Wang Z, Cao K: Analysis of Tumor Microenvironment Characteristics in Bladder Cancer: Implications for Immune Checkpoint Inhibitor Therapy. Front Immunol 2021, 12:672158. (Co-first author)
  5. Chen X*, Lan H*, He D, Xu R, Zhang Y, Cheng Y, Chen H, Xiao S, Cao K: Multi-Omics Profiling Identifies Risk Hypoxia-Related Signatures for Ovarian Cancer Prognosis. Front Immunol 2021, 12:645839. (Co-first author)
  6. Chen X*, Lan H*, He D, Wang Z, Xu R, Yuan J, Xiao M, Zhang Y, Gong L, Xiao S et al: Analysis of Autophagy-Related Signatures Identified Two Distinct Subtypes for Evaluating the Tumor Immune Microenvironment and Predicting Prognosis in Ovarian Cancer. Front Oncol 2021, 11:616133. (Co-first author)
  7. Chen X, Jin Y, Gong L, He D, Cheng Y, Xiao M, Zhu Y, Wang Z, Cao K: Bioinformatics Analysis Finds Immune Gene Markers Related to the Prognosis of Bladder Cancer. Front Genet 2020, 11:607. (First author)
  8. Deng H, Tang F, Zhou M, Shan D, Chen X*, Cao K*: Identification and Validation of N6-Methyladenosine-Related Biomarkers for Bladder Cancer: Implications for Immunotherapy. Front Oncol 2022, 12:820242. (Co-corresponding author)

*These authors contributed equally

Research Experience

Research Bioinformatician I — Cedars-Sinai Medical Center (2022–2024)

  • Led four independent bioinformatics projects on tumor evolution, immunotherapy biomarkers, and spatial proteomics.
  • Supervised two junior scientists, collaborated across six labs, and delivered analyses supporting NIH-funded grants.
  • Published high-impact findings, including a Nature paper on Y-chromosome loss and immune evasion in bladder cancer.

Research Associate I & Visiting Graduate Student — Cedars-Sinai Medical Center (2021–2022)

  • Integrated RNA-seq, ATAC-seq, and single-cell data to explore tumor microenvironment landscapes.
  • Contributed to radiogenomics and multi-modal cancer staging using AI-enhanced MRI and RNA-seq datasets.
  • Co-first author on three peer-reviewed publications during this period.

Early Researcher — Third Xiangya Hospital, Central South University (2020–2021)

  • Conducted immunogenomic analyses on clinical samples from bladder and ovarian cancer patients.
  • Initiated development of PyroScore and IMS scoring systems, which became key predictive models in later publications.

Academic CV

Previous Roles

  • Research Bioinformatician I, Cedars-Sinai Medical Center, 2022.08–2024.07
  • Research Associate I, Cedars-Sinai, 2022.04–2022.08
  • Visiting Graduate Student, Cedars-Sinai, 2021.09–2022.03

Skills

  • Programming: R, Python, Linux
  • Omics: RNA-seq, ATAC-seq, scRNA-seq, DNA methylation, WGS/WES
  • AI/ML: WGCNA, LASSO, Deep Learning, Random Forest
  • Large language model in Genomics: Pretraining & fine-tuning LLMs · genomic transformer Enformer · Borzoi language model · Decima scheduling RL
  • Tools: CellRanger, Seurat, SCENIC, BioRender, Adobe Illustrator

Editorial & Peer Review Roles

  • Youth Editor: iMeta (IF 33.2); Asian Journal of Pharmaceutical Sciences (IF 11.9); Journal of Translational Internal Medicine (IF 7.4) etc.
  • Review Editor: Frontiers in Urology (IF 1.1) etc.
  • Reviewer: iMeta (IF 33.2), Oncogene (IF 7.3), Frontiers in Immunology (IF 5.9), Seminars in Cancer Biology (IF 12.1) etc.

Invited Presentations

  • American Society of Clinical Oncology (ASCO) Annual Meeting 2023:
    • X Chen, M Basu, S Knott, D Theodorescu. CDH12 drives the development of the neuronal subtype in MIBC. Journal of Clinical Oncology 41 (16_suppl), e16579-e16579, 2023 (Abstract)
    • X Chen, T Qureshi, Y Xie, S Knott, D Li, CJ Rosser, H Furuya. Radiogenomics of muscle invasive bladder cancer. Journal of Clinical Oncology 41 (16_suppl), e16587-e16587, 2023 (Abstract)
  • American Urological Association (AUA) Annual Meeting 2023 – Chicago, IL:
    • Oral Presentation, Breakthrough abstract (LBA03-09): X Chen (Speaker), M Basu, S Knott, D Theodorescu. CDH12 Drives The Development Of The Neuronal Subtype in Muscle Invasive Bladder Cancer. The Journal of Urology 209 (Supplement 4), e1195, 2023
    • Oral Presentation, Breakthrough abstract (LBA03-05): TA Qureshi, X Chen (Speaker), Y Xie, K Murakami, T Sakatani, M Miyake, … Radiogenomics Of Muscle Invasive Bladder Cancer. The Journal of Urology 209 (Supplement 4), e1193, 2023
  • American Urological Association (AUA) Annual Meeting 2025 – Las Vegas, NV:
    • Shen Y, Chen X, Choi S, Knott SRV, Theodorescu D. IP14-09 Y Chromosome Loss Promotes Neuroendocrine Differentiation In Bladder Cancer. The Journal of Urology 213(5S): e750, 2025

Contact

Email: xchen295@jh.edu

Location: Baltimore, MD

Download my current CV: PDF Version