Dr. Zhang’s academic journey began in China (BSc, Peking University), continued in the United Kingdom (DPhil, University of Oxford, with Dr. Katja Simon), and the United States (Postdoc, UC Berkeley, with Dr. Andrew Dillin).

The Zhang Lab is interested in the molecular and cellular mechanisms of aging. Leveraging C. elegans, mammalian tissue cultures, and mouse models, we bridge discoveries from cells to organisms, and ultimately to human health. We take advantage of cutting-edge genetics to identify novel genes that regulate cellular homeostasis, cell biology and biochemistry approaches to decode their molecular functions, immunology and physiology experimental systems to assess the physiological impact of our findings on organismal health. Through our research, we seek not only to understand the fundamental biology of aging, but also to translate these discoveries into strategies that promote healthy longevity in humans.

Our previous work revealed that cellular homeostasis is regulated by diverse signals from the microenvironment, i.e. the extracellular matrix (ECM), including fibrous components, cytokines and growth factors, and circulating metabolites. These signals are integrated through crosstalk between the ECM and intracellular organelles – such as nuclei, mitochondria, lysosomes – to regulate cellular function. Currently, the Zhang Lab focuses on:

1) Defining the molecular network of ECM-to-intracellular organelle communication;

2) Exploring how ECM remodelling influences tissue function and aging.

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.