深圳湾实验室2026年1-3月科研动态一览
- 2026-04-18 20:22:13
近期，深圳湾实验室取得了多项研究突破，快来和湾豆一起回顾2026年1月至3月的科研成果吧！以下成果据各课题组、实验室官网整理。
深圳湾实验室分子生理学研究所蔡羽轩课题组和合作者在Journal of the American Chemical Society在线发表了题为Disulfide-directed multicyclic peptides for chimeric antigen receptors targeting solid tumors的研究论文。该研究工作把嵌合抗原受体（CAR）的识别“眼睛”从传统抗体片段（scFv）换成定向二硫键多环肽（DDMP），让CAR T在“该出手时出手”：对抗原高表达肿瘤细胞保持强杀伤；对抗原低表达细胞则显著减少结合与杀伤，同时释放更少促炎细胞因子，从源头降低细胞因子风暴等安全风险。
深圳湾实验室-清华大学发表重要综述：靶向cGAS–STING通路在癌症免疫治疗中的机遇与挑战
深圳湾实验室肿瘤研究所的卢长征研究员、清华大学基础医学院的王文彦助理研究员和傅阳心教授，在Nature Reviews Cancer上发表题为“Opportunities and challenges of targeting cGAS–STING in cancer”的综述文章，系统阐述了cGAS–STING通路在肿瘤发生、发展、转移与治疗中的双重作用，并深入探讨了其作为治疗靶点的潜力与当前困境。
“移花接木”：陈鹏/张衡团队报道膜蛋白靶向降解技术驱动的癌症疫苗新策略
深圳湾实验室/北京大学陈鹏/张衡团队联合席建忠课题组在Nature上发表题为Intratumoural vaccination via checkpoint degradation-coupled antigen presentation的研究论文。该团队在前期系统发展膜蛋白靶向降解（meTPD）技术体系的基础上，着眼于将蛋白降解途径与抗原呈递通路在癌细胞内紧密耦合，成功利用meTPD技术，在解除免疫“刹车”的同时，迫使癌细胞呈递在人体中普遍存在的高质量抗原。这种以肿瘤为出发点的“降解型疫苗”为克服癌症的免疫耐受提供了新的解决策略。
葛韵课题组解锁糖基转移酶OGT非催化新功能用于靶向调控应激颗粒
深圳湾实验室葛韵课题组在Nature Communications发表了题为“Targeted stress granule regulation by engineering a non-catalytic O-GlcNAc transferase”的研究论文。该工作借助化学诱导邻近策略，意外揭示了OGT通过独立于其糖基转移酶活性的非催化功能实现对SG核心蛋白G3BP1的相分离抑制。将靶向元件与OGT的最小结构域组合（N-cat + Int-D）融合后，可以实现对包括G3BP1在内的众多SG组分蛋白发挥相分离抑制功能。通过改变SG的物质性质，该工具可用来干预SG所参与的众多细胞过程，为SG动态调控机制研究及相关疾病病理机制解析提供了全新视角与核心工具。
梁卓斌团队开发活体药物CAT-BLAST平台，瓦解肿瘤基质屏障
深圳湾实验室梁卓斌团队在国际高水平期刊iMeta在线发表了题为 “CAT-BLAST: Engineered Bacteria for Robust Targeting and Elimination of Cancer-Associated Fibroblasts” 的研究论文。该研究开发了一种名为 CAT-BLAST 的工程化细菌平台，通过装备特异性“导航系统”和“爆破装置”，能够精准定位并清除肿瘤微环境中的 CAFs，成功瓦解肿瘤的保护性屏障，为攻克实体瘤耐药性提供了全新的解决策略。
李磊/于晨课题组开发单细胞多模态数据整合算法MAAS
深圳湾实验室系统与物理生物学研究所李磊团队在Genome Medicine上发表了题为Multimodal-based analysis of single-cell ATAC-seq data enables highly accurate delineation of clinically relevant tumor cell subpopulations的研究论文。该研究开发了一种基于单细胞表观组学的多模态整合算法MAAS，实现了对临床相关肿瘤细胞亚群的高精度识别。
深圳湾实验室与深圳医学科学院合作揭示硫解酶复合体的功能重编程机制
深圳湾实验室化学生物学研究所唐啸宇课题组与合作者在国际期刊Nature Communications发表题为“Evolutionary repurposing of a metabolic thiolase complex enables antibiotic biosynthesis”的研究论文。
该研究聚焦于一类由硫解酶家族成员——HMG-CoA synthase (HMGS)和acetyl-CoA acetyltransferase (ACAT)，以及DUF35蛋白组成的多酶复合体。该复合体在古菌中参与甲羟戊酸（mevalonate）合成，是典型的初级代谢酶。然而，该研究发现，在链球菌中HMGS、ACAT和DUF35蛋白组成的硫解酶复体在保守结构框架上通过活性口袋重构，获得了催化非经典的傅-克酰基化反应的新功能，从而完成抗生素reutericyclin A生物合成的关键步骤。
饶浪课题组与合作团队开发3D打印原位树突细胞疫苗用于肿瘤术后治疗
深圳湾实验室饶浪课题组与合作者在知名期刊National Science Review发表了题为In situ generation of dendritic cell vaccines in 3D printing scaffolds for cancer post-surgical therapy的研究论文。研究团队成功开发了一种基于3D生物打印技术的原位树突状细胞（DC）疫苗，可实现体内直接高效诱导预载细胞分化成熟，显著激发系统性抗肿瘤免疫以抑制肿瘤术后复发，并在前列腺癌模型中展现出优异的抗转移与“骨保护”治疗效果。这一成果成功破解了传统DC疫苗依赖复杂体外制备的转化难题，有望为个性化肿瘤术后治疗开辟更加简便、高效的新路径。
黄湧/陈杰安团队：手性α,α-双杂原子羧酸的高效可控合成
香港科技大学黄湧教授与深圳湾实验室陈杰安研究员团队在手性合成与药物分子砌块领域取得重要突破，相关研究成果以Harnessing thia-Rh-carbenes for the enantioselective synthesis of chiral α,α-diheteroatomic carboxylic acids为题，在线发表于国际顶级催化期刊《自然 催化》（Nature Catalysis）。
冯根生团队提出肝癌治疗新策略：肝靶向递送突破免疫治疗瓶颈
3月11日，SCIENCE CHINA Life Sciences（《中国科学：生命科学》英文版）在线发表了深圳湾实验室肿瘤研究所冯根生研究员撰写的题为“Advancing liver cancer immunotherapy beyond checkpoint blockade”的Insight文章，简要总结了肝癌免疫治疗的现状与困境，并提出了一种不依赖免疫检查点抑制剂的肝靶向免疫治疗新策略。原发性肝癌，是全球癌症死亡的第三大原因。在我国，相当比例的肝癌病例与乙型肝炎病毒感染相关。尽管基础研究投入巨大，但该恶性肿瘤仍缺乏一高效的治疗药物。
彭琴课题组揭示Lamin B1非泛素化降解力学响应机制及其对成肌分化的关键调控作用
深圳湾实验室彭琴课题组、重庆大学邱菊辉课题组与华南理工大学李趣欢等合作在EMBO Reports上在线发表了题为 Matrix Stiffness Induces Midnolin-dependent Lamin B1 Degradation to Control Myoblast Differentiation 的最新研究成果。该研究发现，软基质力学微环境中，成肌细胞里的核纤层蛋白Lamin B1水平显著下降，分化能力严重受阻。主要分子机制是软基质刚度启动了Midnolin与Lamin B1互作，通过非泛素依赖的蛋白酶体降解途径显著下调Lamin B1水平，来响应外界不适的力学微环境。阻断Midnolin-Lamin B1通路可挽救软基底引起的成肌分化缺陷。因此，维持适度的Lamin B1水平才能保证成肌细胞的正常分化。换句话说，成肌细胞的分化如同在不同硬度的基石上构建大厦，Lamin B1则是支撑核心的‘动态支架’。只有根据分化阶段精准调节支架的强度，细胞才能顶住环境压力，最终发育成形态稳固、功能完备的成熟建筑。
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