Xingyu Chen · Medicine meets computational discoveryXingyu Chen · 连接医学与计算发现
Understanding immune dysfunction to advance healthy longevity and cancer immunotherapy.解析免疫功能障碍，推动健康长寿与癌症免疫治疗。
I connect medical and oncology training with immunology, computational biology, and AI to identify what changes in immune cells—and which mechanisms are worth testing.我将医学与肿瘤学训练、免疫学研究、计算生物学和 AI 相结合，解析免疫细胞发生了什么变化，以及哪些机制值得进一步验证。
Why this research matters为什么这一研究重要
How can immune cells maintain, adapt, and recover appropriate function across age, disease, and treatment? This question connects my two long-term goals.免疫细胞如何在年龄增长、疾病与治疗的挑战下维持、适应并恢复适当功能？这一问题连接着我的两条长期研究目标。
Healthy aging · Healthspan · Lifespan健康衰老 · 健康寿命 · 寿命研究
Investigate how age-related changes compromise immune function, and whether targeted interventions can delay functional decline, extend healthspan, and support longer life.研究年龄相关变化如何损害免疫功能，探索针对性干预能否延缓功能衰退、延长健康寿命，并进一步支持寿命延长。
Immune escape · T-cell function · Durable response免疫逃逸 · T 细胞功能 · 持久应答
Determine what limits effective antitumor immunity, then identify mechanisms and cellular contexts that could improve the depth and durability of immunotherapy responses.解析限制抗肿瘤免疫的关键因素，识别可干预机制及适用的细胞情境，以改善免疫治疗应答的深度与持久性。
A connected research program相互衔接的研究主线
My published work connects age-associated genomic variation, cellular stress, and transcriptional regulation to the behavior of immune cells.我的已发表研究连接年龄相关基因组变化、细胞应激与转录调控，聚焦它们如何影响免疫细胞的功能。
Y-chromosome loss is an age-associated feature of male biology—and a direct link between my cancer research and questions of immune aging.Y 染色体丢失是男性随年龄增长而更常见的体细胞变化，也连接着我的癌症研究与免疫老化问题。
Our LOY studies show how a genomic change can affect the tumor–immune ecosystem. My work on proteotoxic stress and CD8+ T-cell differentiation extends the focus to how immune cells lose, maintain, or acquire function.我们的 LOY 研究揭示基因组改变如何影响肿瘤与免疫生态；我参与的蛋白毒性应激与 CD8+ T 细胞分化研究，则进一步探索免疫细胞如何失去、维持或获得功能。
The aging–immunity connection阅读衰老与免疫的研究联系
Current research directions当前研究方向
Building on published discoveries to identify which changes are reversible, in which cells, and under what conditions.以已发表发现为基础，进一步研究哪些变化可能被逆转、发生在哪些细胞中，以及需要什么条件。
Which age-related genomic and stress programs compromise immune function—and which remain open to intervention? I am extending these questions to immune-cell states, mitochondrial biology, and tissue context.哪些年龄相关基因组变化和应激程序会损害免疫功能，哪些仍有干预空间？我正在将这些问题拓展至免疫细胞状态、线粒体生物学和组织环境。
Foundation: LOY biology. Long-term aim: healthy longevity.研究基础：LOY 生物学。长期目标：健康长寿。
How do protein homeostasis and transcriptional programs control T-cell exhaustion and cytotoxic function? I am interested in how these mechanisms could inform checkpoint blockade and immune-cell therapies, including CAR-T.蛋白质稳态与转录程序如何控制 T 细胞耗竭及细胞毒性功能？我关注这些机制如何为免疫检查点治疗与 CAR-T 等免疫细胞疗法提供依据。
Foundation: Nature 2025 and Nature Immunology 2026.研究基础：Nature 2025 与 Nature Immunology 2026。
Can human multi-omics and perturbation-informed models identify the next experiment? My developing direction combines regulatory modeling, virtual perturbations, and context-specific cell models with independent and functional validation.人类多组学与结合扰动证据的模型，能否帮助选出下一个关键实验？我正在探索调控建模、虚拟扰动及特定情境下的细胞模型，并用独立数据和功能实验检验预测。
Foundation: published ML and multimodal analyses. Frontier: predictive perturbation models.研究基础：已发表的机器学习与多模态分析。前沿探索：扰动预测模型。
How I work研究方法
AI becomes useful when it helps decide which mechanism, target, or experiment deserves attention in a specific biological context.AI 的研究价值，在于帮助判断特定生物学情境下，哪些机制、靶点或实验值得优先关注。
Integrate single-cell, spatial, genomic, and clinical data to resolve cells, tissues, and patient differences.整合单细胞、空间、基因组与临床数据，解析细胞、组织和患者差异。
Build reproducible multimodal models that connect cellular programs to measurable biological and clinical outcomes.建立可复现的多模态模型，将细胞程序连接到可测量的生物学与临床结局。
Develop regulatory and cell-state models to prioritize candidate interventions and the contexts in which to test them.探索调控与细胞状态模型，筛选候选干预及适合开展验证的细胞情境。
Connect predictions to perturbation data and collaborative experiments; revise hypotheses when evidence changes.通过真实扰动数据与合作实验检验预测，并依据新证据修正假设。
The output is a sharper research decision: what to test, where to test it, and what result would change our understanding.让研究决策更清楚：验证什么、在哪里验证，以及什么结果会改变我们对机制的判断。
Selected discoveries代表性发现
From Y-chromosome loss to T-cell stress and differentiation: complementary studies of how immune function is shaped—and where it might be modified.从 Y 染色体丢失到 T 细胞应激与分化：这些研究共同探索免疫功能如何被塑造，以及潜在的干预切入点。
Concurrent Y-chromosome loss in cancer cells and T cells is associated with immune dysfunction and poorer survival.发现肿瘤细胞与 T 细胞并存的 Y 染色体丢失与免疫功能障碍及较差生存结局相关。
Age-associated genomic change → tumor–immune function年龄相关基因组改变 → 肿瘤与免疫细胞功能
My contribution:我的贡献： Study design, computational methodology, bioinformatics and statistical analysis, and manuscript writing.研究设计、计算方法、生物信息与统计分析、论文写作。
Tumor-cell Y loss promotes T-cell exhaustion and immune escape in bladder cancer, while increasing sensitivity to PD-1 blockade.发现膀胱癌细胞 Y 染色体丢失可促进 T 细胞耗竭和免疫逃逸，同时提高对 PD-1 阻断治疗的敏感性。
Genomic alteration → immune escape and treatment response基因组改变 → 免疫逃逸与治疗应答
My contribution:我的贡献： Human-sample statistical analyses and interpretation.人类样本统计分析与结果解读。
Identifies disrupted protein homeostasis as a driver of T-cell exhaustion, revealing potential intervention points for cancer immunotherapy.发现蛋白质稳态失衡可驱动 T 细胞耗竭，为癌症免疫治疗提供潜在干预切入点。
Protein homeostasis → maintenance of T-cell function蛋白质稳态 → T 细胞功能维持
My contribution:我的贡献： Collection and analysis of pan-cancer single-cell RNA-sequencing datasets.泛癌单细胞 RNA 测序数据收集与分析。
Identifies ZFP148 as a brake on cytolytic CD8+ T-cell differentiation and a potential target for strengthening antitumor immunity.发现 ZFP148 抑制细胞毒性 CD8+ T 细胞分化，为增强抗肿瘤免疫提供潜在靶点。
Transcriptional regulation → cytotoxic effector function转录调控 → 细胞毒性效应功能
My contribution:我的贡献： Analysis of integrated single-cell RNA-sequencing data from human cancers.对整合后的人类肿瘤单细胞 RNA 测序数据进行分析。
A complementary clinical application: combining imaging and molecular data to improve bladder-cancer staging models.面向临床问题的多模态应用：结合影像与分子数据，改进膀胱癌分期模型。
Long-term translational horizon长期转化愿景
I aim to translate mechanisms of immune dysfunction into interventions for healthy aging and cancer. The next questions are which target, in which cell or patient context, and with what functional evidence.我希望将免疫功能障碍的机制发现，转化为面向健康衰老与癌症的干预策略。关键是明确靶点、适用的细胞或患者情境，以及支持干预的功能证据。
Depending on the biology, future approaches may include RNA interventions, therapeutic combinations, and immune-cell engineering.依据具体生物学机制，未来可探索 RNA 干预、治疗组合与免疫细胞工程。
Why collaborate with me为什么选择与我合作
For academic, biotech, and translational teams pursuing immune aging, healthy longevity, or cancer immunotherapy.面向研究免疫老化、健康长寿或癌症免疫治疗的学术、生物技术与转化研究团队。
I bring medical and oncology training together with hands-on human multi-omics research and published immunology work—connecting a clinically meaningful question to a mechanism and a focused validation plan.我将医学与肿瘤学训练、人类多组学研究实践，以及已发表的免疫学工作相结合，把有临床意义的问题连接到具体机制与聚焦的验证方案。
Medical and oncology training helps connect cell-state findings to patient context, treatment response, and the biological question that matters.医学与肿瘤学训练帮助我把细胞状态的发现，连接到患者背景、治疗应答与真正重要的生物学问题。
Together: a focused question, relevant cohort, and meaningful endpoint.共同形成：聚焦的问题、相关队列与有意义的研究终点。
Experience with pan-cancer, single-cell, and spatial analyses supports evaluating where a target acts, how consistent the signal is, and what contradicts it.泛癌、单细胞与空间分析经验，支持评估靶点在哪些细胞中发挥作用、证据是否一致，以及存在哪些相反证据。
Together: reproducible analyses and evidence-based target prioritization.共同形成：可复现分析与基于证据的靶点排序。
Computational modeling and published work on T-cell dysfunction help turn associations into explicit hypotheses for experimental collaborators.计算建模与 T 细胞功能障碍研究经验，帮助将关联转化为明确假设，与实验合作者共同检验。
Together: candidate perturbations, functional readouts, and decision criteria.共同形成：候选扰动、功能读出与研究判断标准。
For discovery teams and scientific partners: I welcome discussions on target rationale, human relevance, and experiments that can clarify the next research or translational investment decision.面向发现研究团队与科学合作伙伴：欢迎讨论靶点依据、人类相关性，以及能为下一步科研或转化投入提供判断的关键实验。
Discuss a research question讨论研究合作 ↗News & recognition报道与认可
Selected coverage and recognition related to my research program.与我的研究方向相关的部分报道和学术讨论。
Nature News covered our 2025 study on Y-chromosome loss across cancer and immune cells.Nature News 报道了我们的 2025 年研究，讨论肿瘤细胞与免疫细胞中的 Y 染色体丢失如何影响癌症结局。
Background个人背景
My training spans clinical medicine, oncology, and doctoral research coursework and rotations. At Cedars-Sinai, my research connects computational genomics with tumor immunology and clinically grounded questions.我的训练经历涵盖临床医学、肿瘤学及博士阶段课程与实验室轮转。在 Cedars-Sinai 的研究工作中，我将计算基因组学与肿瘤免疫学相结合，关注具有临床意义的科学问题。
I also contribute through peer review, editorial service, mentoring, and Prostate Cancer Foundation young-investigator working groups.我也通过同行评议、编辑服务、研究指导，以及 Prostate Cancer Foundation 青年研究者工作组参与学术共同体建设。
Immune aging, healthy longevity, T-cell function, and cancer immunotherapy. Let’s explore where our questions and expertise meet.免疫老化、健康长寿、T 细胞功能与癌症免疫治疗。期待探讨我们研究问题与专业能力的交汇之处。