张汉林实验室的主要兴趣方向为衰老（aging）。作为每个成年个体都正在亲身经历的生命历程，衰老现象始终激发着人类深刻的好奇心与同理心。随着20世纪末一系列衰老研究奠基性发现的问世，人类已经认识到衰老过程背后存在着复杂但有规律、可调控的的分子与细胞学机制。研究这一现象不仅具有助于揭示生命运行的基本规律，也在预防和治疗衰老相关疾病如神经退行、癌症、心脑血管疾病等方面具有重要的应用价值。基于前期在细胞自噬、线粒体胁迫、胞外基质重塑、免疫调控等衰老相关领域的积累，本课题组将以“细胞稳态调控的分子机制“为核心研究方向，综合利用线虫、组织培养、小鼠等多种生物模型，结合细胞生物学、遗传学、分子生物学、免疫学、多组学分析等技术手段，从现象到机制、从分子到整体对衰老相关科学问题进行系统性探索。

具体研究方向包括：

（1）细胞内外稳态的调节与通讯机制；

（2）细胞稳态信号通路对机体免疫和衰老的调节；

（3）组织纤维化等衰老相关病变的发生与干预。

1.    Zhang, H., Tsui, C.K., Garcia, G., Joe, L.K., Wu, H., Maruichi, A., Fan, W., Pandovski, S., Yoon, P.H., Webster, B.M., et al. (2024). The extracellular matrix integrates mitochondrial homeostasis. Cell 187, 4289-4304.e26. https://doi.org/10.1016/j.cell.2024.05.057.

2.    Zhang, H.#, Tsui, C.K.#, Castillo, J.G., Evangelista, A., Kim, E.J.Y., Joe, L.K., Twells, N., Robey, E.A., Mahal, L.K., DuPage, M., et al. (2024). Age-related remodeling of the glycocalyx drives T cell exhaustion. Preprint (bioRxiv), https://doi.org/10.1101/2024.12.06.627213. (# co-first)

3.    Zhang, H.#, Li, X.#, Fan, W., Pandovski, S., Tian, Y., and Dillin, A. (2023). Inter-tissue communication of mitochondrial stress and metabolic health. Life Metabolism, load001. https://doi.org/10.1093/lifemeta/load001. (# co-first)

4.    Zhang, H.*, and Simon, A.K. (2020). Polyamines reverse immune senescence via the translational control of autophagy. Autophagy 16, 181–182. https://doi.org/10.1080/15548627.2019.1687967. (* corresponding)

5.    Zhang, H., Alsaleh, G., Feltham, J., Sun, Y., Napolitano, G., Riffelmacher, T., Charles, P., Frau, L., Hublitz, P., Yu, Z., et al. (2019). Polyamines Control eIF5A Hypusination, TFEB Translation, and Autophagy to Reverse B Cell Senescence. Molecular Cell 76, 110-125.e9. https://doi.org/10.1016/j.molcel.2019.08.005.

6.    Zhang, H., Puleston, D.J., and Simon, A.K. (2016). Autophagy and Immune Senescence. Trends in Molecular Medicine 22, 671–686. https://doi.org/10.1016/j.molmed.2016.06.001.

7.    Murley, A., Popovici, A.C., Hu, X.S., Lund, A., Wickham, K., Durieux, J., Joe, L., Koronyo, E., Zhang, H., Genuth, N.R., et al. (2025). Quiescent cell re-entry is limited by macroautophagy-induced lysosomal damage. Cell 188, 2670-2686.e14. https://doi.org/10.1016/j.cell.2025.03.009.

8.    Shen, K., Durieux, J., Mena, C.G., Webster, B.M., Tsui, C.K., Zhang, H., Joe, L., Berendzen, K.M., and Dillin, A. (2024). The germline coordinates mitokine signaling. Cell 187, 4605-4620.e17. https://doi.org/10.1016/j.cell.2024.06.010.

9.    Garcia, G., Zhang, H., Moreno, S., Tsui, C.K., Webster, B.M., Higuchi-Sanabria, R., and Dillin, A. (2023). Lipid homeostasis is essential for a maximal ER stress response. eLife 12, e83884. https://doi.org/10.7554/eLife.83884.

10.  Shen, K., Pender, C.L., Bar-Ziv, R., Zhang, H., Wickham, K., Willey, E., Durieux, J., Ahmad, Q., and Dillin, A. (2022). Mitochondria as Cellular and Organismal Signaling Hubs. Annu. Rev. Cell Dev. Biol. 38, 179–218. https://doi.org/10.1146/annurev-cellbio-120420-015303.

11.  Leng, H., Zhang, H., Li, L., Zhang, S., Wang, Y., Chavda, S.J., Galas-Filipowicz, D., Lou, H., Ersek, A., Morris, E.V., et al. (2022). Modulating glycosphingolipid metabolism and autophagy improves outcomes in pre-clinical models of myeloma bone disease. Nat Commun 13, 7868. https://doi.org/10.1038/s41467-022-35358-3.

12.  Puleston, D.J., Zhang, H., Powell, T.J., Lipina, E., Sims, S., Panse, I., Watson, A.S., Cerundolo, V., Townsend, A.R., Klenerman, P., et al. (2014). Autophagy is a critical regulator of memory CD8+ T cell formation. eLife 3, e03706. https://doi.org/10.7554/eLife.03706.

13.  Simon, A.K., Obba, S., Zhang, H., and Riffelmacher, T. (2019). Autophagy in the Hematopoietic System. Blood 134, SCI-44-SCI-44. https://doi.org/10.1182/blood-2019-121093.

14.  Alsaleh, G., Panse, I., Swadling, L., Zhang, H., Richter, F.C., Meyer, A., Lord, J., Barnes, E., Klenerman, P., Green, C., et al. (2020). Autophagy in T cells from aged donors is maintained by spermidine and correlates with function and vaccine responses. eLife 9, e57950. https://doi.org/10.7554/eLife.57950.

15.  Garcia, G., Bar‐Ziv, R., Averbukh, M., Dasgupta, N., Dutta, N., Zhang, H., Fan, W., Moaddeli, D., Tsui, C.K., Castro Torres, T., et al. (2022). Large‐scale genetic screens identify BET ‐1 as a cytoskeleton regulator promoting actin function and life span. Aging Cell. https://doi.org/10.1111/acel.13742.

16.  Dishart, J.G., Pender, C.L., Shen, K., Zhang, H., Ly, M., Webb, M.B., and Dillin, A. (2024). Olfaction regulates peripheral mitophagy and mitochondrial function. Sci. Adv. 10, eadn0014. https://doi.org/10.1126/sciadv.adn0014.

17.  Moehle, E.A., Higuchi-Sanabria, R., Tsui, C.K., Homentcovschi, S., Tharp, K.M., Zhang, H., Chi, H., Joe, L., de los Rios Rogers, M., Sahay, A., et al. (2021). Cross-species screening platforms identify EPS-8 as a critical link for mitochondrial stress and actin stabilization. Sci. Adv. 7, eabj6818. https://doi.org/10.1126/sciadv.abj6818.