Larry L. Hillbloom Research Fellow
Research
I received my bachelor’s degree in biology from Peking University in China and my DPhil in clinical medicine from the University of Oxford in the UK. My research primarily focuses on unraveling the molecular mechanisms underlying the aging process. During my DPhil in Prof Katja Simon’s lab, I studied how autophagy regulates aging of the mammalian immune system. I discovered that the polyamine metabolism regulates autophagy and B-cell aging via translational control of TFEB expression. This finding directly led to an exciting clinical trial aimed at enhancing the efficacy of COVID-19 and influenza vaccinations through the use of polyamines.
In the Dillin lab, I am interested in understanding how cells can perceive stress in the cellular microenvironment and subsequently undergo adaptive alterations to their mitochondria. By combining different research systems from C. elegans and cultured mammalian cells to mouse models, I aim to explore the intricate inter-organellar communication mechanisms and assess their influence on the aging process.
Representative publications
Zhang H, Alsaleh G, Feltham J, Sun Y, Napolitano G, et al. Polyamines control eIF5A hypusination, TFEB translation and autophagy to reverse B cell senescence. Molecular cell 2019; 76:110-25.
Zhang H, Simon AK. Polyamines reverse immune senescence via the translational control of autophagy. Autophagy 2020; 1:181-2.
Zhang H, Puleston DJ, Simon AK. Autophagy and Immune Senescence. Trends in molecular medicine 2016; 22:671-86.
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. 10.1093/lifemeta/load001.
Puleston DJ, Zhang H, Powell TJ, Lipina E, Sims S, Panse I, et al. Autophagy is a critical regulator of memory CD8(+) T cell formation. eLife 2014; 3.
Garcia, G., Zhang, H., Moreno, S., Kimberly Tsui, C., Webster, B.M., Higuchi-Sanabria, R., and Dillin, A. (2023). Lipid homeostasis is essential for a maximal ER stress response. bioRxiv/eLife.
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. 10.1038/s41467-022-35358-3.
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, e57950.0.7554/eLife.57950.
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. 10.1146/annurev-cellbio-120420-015303.
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. 10.1126/sciadv.abj6818.
Frankino, P.A., Siddiqi, T.F., Bolas, T., Bar-Ziv, R., Gildea, H.K., Zhang, H., Higuchi-Sanabria, R., and Dillin, A. (2022). SKN-1 regulates stress resistance downstream of amino catabolism pathways. iScience 25, 104571. 10.1016/j.isci.2022.104571.
Yu Z, Huang H, Zhang H, Kessler BM. Improved profiling of polyamines using two-dimensional gas chromatography mass spectrometry. Talanta 2019; 199:184-8.
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 lifespan. Aging Cell. 10.1111/acel.13742.
Fu X, Shi X, Yan L, Zhang H, Chang Z. In vivo substrate diversity and preference of small heat shock protein IbpB as revealed by using a genetically incorporated photo-cross-linker. The Journal of biological chemistry 2013; 288:31646-54.
Shi X, Yan L, Zhang H, Sun K, Chang Z, Fu X. Differential degradation for small heat shock proteins IbpA and IbpB is synchronized in Escherichia coli: implications for their functional cooperation in substrate refolding. Biochemical and biophysical research communications 2014; 452:402-7.