神经退行性疾病，如帕金森病，影响全球超千万人，随着人口老龄化加剧，患者数量仍在快速增长。过去几十年里，领域内在神经退行性疾病遗传及病理机制方面取得了一系列进展，但目前全球范围内仍缺乏有效的治疗手段，这反映我们对疾病的认识尚不全面，关键的疾病调控分子和干预手段亟待发掘。

长期以来，神经退行性疾病的研究受制于三个局限：1）疾病模型与病理差异：错误折叠蛋白的积累是神经退行性疾病的关键病理特征，但常用细胞或动物模型（如小鼠）无法自发形成这类病理改变。通过外源导入或基因过表达构建的模型，与真实病理状态存在显著差异。2）衰老环境差异：神经退行性疾病与衰老密切相关，然而常用的啮齿类模型（包括寿命长达30年的裸鼹鼠）本身不易罹患这类疾病或癌症，提示其衰老特征与人类差异较大，导致许多在这些动物模型中成功的发现和疗法在人类临床转化成功率不高。3）研究视野局限：神经退行性疾病涉及多种细胞、组织和系统层面的复杂互作，既往研究多集中于神经元，且停留在基于假设驱动推断的有限数目基因研究层面，缺乏对疾病机制全基因组、多细胞类型的系统性解析。

尹江安课题组以帕金森病为研究重点，尝试以新的策略和科学视角突破上述瓶颈。我们依托实验室前期建立的高通量CRISPR阵列筛选平台，结合可保留衰老微环境的人类老年细胞模型，以及能够自发形成错误折叠蛋白累积的新型灵长类动物活体模型，综合利用人类遗传学及人的样品，系统解析疾病机制并挖掘潜在治疗靶点。该前沿性探索也希望为其他神经退行性疾病的研究提供新的借鉴。

具体研究方向包括：1）系统解析GBA1（帕金森病最大风险基因）突变诱发帕金森病的机制；2）系统探索衰老如何驱动帕金森病，发掘与错误折叠蛋白通路并行的关键致病基因；3）开发新型研究工具、系统探索基因组中暗物质（intergenic DNA sequences）在衰老与神经退行性疾病中的潜在作用。

尹江安一直致力于神经系统衰老和退行性病的研究，取得了一系列重要成果：1) 揭示了寿命和健康寿命具有不等同的调节机制，明确了神经递质在动物行为和认知功能退化中的重要作用，推动衰老研究从关注寿命延长至健康寿命的新方向; 2）首次解析了健康衰老的遗传基础、发现了新的神经肽及其受体介导的胶质细胞—神经元通路调控衰老速度；3) 构建了新型CRISPR阵列筛选系统，实现了对人类蛋白编码基因全覆盖的精准激活、敲除和沉默，极大地拓展了CRISPR筛选的表型范畴；为神经退行性疾病及诸多生物医学难题研究建立了基础性工具; 4）发明了高通量、低成本慢病毒包装技术，首次测定了慢病毒基因组重组对于CRISPR筛选结果的影响，提出了经济、高效的解决方案；5) 发现了一系列新的调控帕金森病和朊蛋白病的基因和复合物，部分基因有成为药物作用靶点的潜力。以第一作者或共同通讯作者在Nature、Nature Biomedical Engineering、 npj Parkinson’s Disease和Journal of Neuroscience等期刊发表论文6篇，以共同作者发表论文10 余篇。

尹江安担任Nature Communications, Seminars in Immunology, iScience等杂志审稿人和Frontiers in Genetics杂志客座编辑。

2025 瑞士Georg Friedrich Götz奖（早期职业成就奖，华人首次）

2022 瑞士Dementia Research Switzerland - Synapsis Foundation 职业发展奖 （支持博士后向独立研究员转变）

2023 中国上海市自然科学一等奖（第三完成人）

2016 第七届亚太线虫会议最佳报告奖

2015 受邀参加第65届林岛诺贝尔奖获得者大会

1. Yin JA, Frick L, Scheidmann M. C, Liu T, Trevisan C, Dhingra A, Spinelli A, Wu Y, Yao L, Vena DL, Knapp B, Cecco E. D, Ging K, Armani A, Oakeley E, Nigsch F, Jenzer J, Haegele J, Pikusa M, Täger J, Rodriguez-Nieto S, Guo J, Bouris V, Ribeiro R, Baroni F, Bedi M, Berry S, Losa M, Hornemann S, Kampmann M, Pelkmans L, Hoepfner D, Heutink P, Aguzzi A. (2024). Arrayed CRISPR libraries for the genome-wide activation, deletion and silencing of human protein-coding genes. Nature Biomedical Engineering. https://www.nature.com/articles/s41551-024-01278-4.

Jiang-An Yin, first- and co-corresponding author. We established a massively parallel liquid-phase plasmid cloning technique and generated two genome-wide CRISPR ARRAYED libraries for one-by-one activation, ablation, or silencing of human protein-coding genes. This tool significantly extends the territory of CRISPR screens and unlocks pooled-library-inaccessible realms of biomedical research.

2. Yin JA, Gao G, Liu XJ, Hao ZQ, Li K, Kang XL, Li H, Shan YH, Hu WL, Li HP, and Cai SQ (2017). Genetic variation in glia-neuron signalling modulates ageing rate. Nature. 2017;551(7679):198-203. https://www.nature.com/articles/nature24463.

Jiang-An Yin, first-author. This work uncovered the first genetic basis of natural variation in aging rate and identified a novel neuropeptide-mediated glia-neuron signaling regulating healthy aging. This is one of the first groundbreaking studies in healthy aging research.

3. Yin JA, Liu XJ, Yuan J, Jiang J, Cai SQ (2014). Longevity manipulations differentially affect serotonin/dopamine levels and behavioral deterioration in aging Caenorhabditis elegans. Journal of Neuroscience. 2014;34(11):3947-58. https://pubmed.ncbi.nlm.nih.gov/24623772/.

Jiang-An Yin, first-author. This work uncovered that lifespan extension is uncoupled with health span and has opened a new avenue for healthy aging research.

4. Ging K, Frick L, Schlachetzki J, Armani A, Zhu Y, Gilormini P-A, Dhingra A, Böck D, Marques A, Pisano C, Deen M, Chen X, Serdiuk T, Trevisan C, Sellitto S, Glass K C, Heutink P, Yin JA, Vocadlo JD, Aguzzi A (2024). Direct and indirect regulation of β-glucocerebrosidase by the transcription factors USF2 and ONECUT2. npj Parkinson’s Disease 2024,10(1):p192. https://www.nature.com/articles/s41531-024-00819-7.

Jiang-An Yin, co-corresponding author. This work employed our CRISPR arrayed library T.gonfio and for the first time identified the transcription factors regulating the transcriptional expression and enzymatic activity of β-glucocerebrosidase, whose mutations are the most common risk factors for Parkinson's disease.

5. Yin JA, Cai S-Q (2014). Roles of dopaminergic signaling in behavioral and cognitive decline in aging animals. Chemistry of Life, 2014, 34, 176-183. http://www.life.ac.cn/artsmore.asp?id=407.

Jiang-An Yin, first-author. This work systematically summarized the roles of dopamine signaling in mammalian aging with a focus on behavioral and cognitive deteriorations.

6. Xu YP, Yin JA, Shao ZY. Genetic and Molecular Mechanisms of Healthy Aging and Age-related Diseases. Frontiers in Genetics, 2024, 15, p.1509961. https://pubmed.ncbi.nlm.nih.gov/39525813/.

Jiang-An Yin, co-corresponding author. This work summarized the collection of papers published in Frontiers in Genetics with Jiang-An Yin as one of the handling editors.

7. Liu TT, Li HY, Gu SY, Sun L, Zhang RW, Zhu JL, Zhang Y, Yu SG, Zheng XD, Yin JA, Chen Q, He J, Xu B, Du JL. NMDA receptors coordinate brain vascular development via neuron-to-endothelial tip cell crosstalk. Nature Communications accepted.

8. Company C, Schmitt M J, Dramaretska Y, Serresi M, Kertalli S, Jiang B, Yin JA, Aguzzi A, Barozzi I, Gargiulo G (2024). Logical design of synthetic cis-regulatory DNA for genetic tracing of cell identities and state changes. Nature Communications. https://www.nature.com/articles/s41467-024-45069-6.

9. Avar M, Heinzer D, Thackray AM, Liu Y, Hruska-Plochan M, Sellitto S, E. Schaper, D. P. Pease, Yin JA, Lakkaraju AK, Emmenegger M, Losa M, Chincisan A, Hornemann S, Polymenidou M, Bujdoso R, Aguzzi A (2022). An Arrayed Genome-Wide Perturbation Screen Identifies the Ribonucleoprotein hnRNP K As Rate-Limiting for Prion Propagation. EMBO J. 2022: p. e112338. https://pubmed.ncbi.nlm.nih.gov/36254605/.

10. Heinzer D, Avar M, Pease DP, Dhingra A, Yin JA, Schaper E, Dogancay B, Emmenegger M Spinelli A, Maggi K, Chincisan A, Mead S, Hornemann S, Heutink P, Aguzzi A (2021). Novel regulators of PrPC biosynthesis revealed by genome-wide RNA interference. PLoS Pathog. 2021;17(10):e1010013. https://pubmed.ncbi.nlm.nih.gov/34705895/.

11. Yuan J, Chang SY, Yin SG, Liu ZY, Cheng X, Liu XJ, Jiang Q, Gao G, Lin DY, Kang XL, Ye SW, Chen Z, Yin JA, Hao P, Jiang L and Cai SQ (2020). Two conserved epigenetic regulators prevent healthy ageing. Nature. 2020;579(7797):118-22. https://pubmed.ncbi.nlm.nih.gov/32103178/.

12. Liu TT, Du XF, Zhang BB, Zi HX, Yan Y, Yin JA, Hou H, Gu SY, Chen Q, Du JL (2020). Piezo1-Mediated Ca(2+) Activities Regulate Brain Vascular Pathfinding during Development. Neuron. 2020;108(1):180-92 e5. https://pubmed.ncbi.nlm.nih.gov/32827455/.

13. Zhou ZL, Jiang J, Yin JA, Cai SQ (2014). Identifying interacting proteins of a Caenorhabditis elegans voltage-gated chloride channel CLH-1 using GFP-Trap and mass spectrometry. Acta Physiologica Sinica. 2014;66(3):341-8. https://pubmed.ncbi.nlm.nih.gov/24964852/.

14. Sellitto S, Caredio D, Bimbati M, Cerisoli M, Frick L, Vena DL, Neupane S, Baroni F, Ging K, Yin JA, Armani A, and Aguzzi A. Prion propagation is controlled by a hierarchical network involving the nuclear Tfap2c and hnRNP K factors and the cytosolic mTORC1 complex. bioRxiv, https://www.biorxiv.org/content/10.1101/2024.10.21.619371v2.full.

15. Neupane S, Nikolić L, Maraio L, Goiran T, Karpilovsky N, Sellitto S, Bouris V, Yin JA, Melki R, Fon EA, De Cecco E, Aguzzi A. Large-scale bidirectional arrayed genetic screens identify OXR1 and EMC4 as modifiers of α-synuclein aggregation, bioRxiv, https://www.biorxiv.org/content/10.1101/2025.06.10.658866v2.full.

16. Yang CC, Deshpande AJ, Jackson M, Adams PD, Lynch D, Gibson AV, Waqar ZK, Beketova A, Yin JA, Huang CT. Automation of high-throughput arrayed mammalian cell line cultivation. bioRxiv, https://www.biorxiv.org/content/10.1101/2025.10.03.676043v1.full.

17. Yang CC, Deshpande AJ, Jackson M, Adams PD, Altman Y, Yin JA, Wu YC, Post MA, Beketova A, Huang CT. Automation of high-throughput arrayed lentivirus production and titration. bioRxiv, https://www.biorxiv.org/content/10.1101/2025.10.04.680488v1.full.

专利

Yin JA, Aguzzi A, Frick L. Molecular Cloning Method and Vector therefore. Patent. WO/2023/089153, 2023.