The Hu lab is interested in studying molecular and cellular mechanisms involved in neurodegeneration, particularly Amyotrophic Lateral Sclerosis (ALS) and Frontotemporal Lobar Degeneration (FTLD). Using a combination of biochemical and cell biological approaches and mouse models, the Hu lab aims to elucidate cellular and physiological functions of several ALS/FTLD genes, including granulin, TMEM106B, C9orf72 and TDP-43. We have discovered interesting links between lysosomal dysfunction and neurodegeneration. We hope that our studies will not only shed light on the molecular and cellular mechanisms of ALS/FTLD but also facilitate therapeutic development for these devastating diseases.
Selected Publications
Du H, Zhou X, Feng T and Hu F. Regulation of progranulin trafficking by sortilin and prosaposin Brain Commun. 2022 Jan 4;4(1):fcab310. doi:10.1093/braincomms/fcab310.
Zhang T, Du H, Santos M, Wu X, Pagan MD, Trigiani LJ, Nishimura N, Reinheckel T, Hu F. Differential regulation of progranulin derived granulin peptides. Mol Neurodegener. 2022 Feb 4;17(1):15. doi: 10.1186/s13024-021-00513-9.
Huan Du, Man Ying Wong, Tingting Zhang, Mariela Nunez Santos, Charlene Hsu, Junke Zhang, Haiyuan Yu, Wenjie Luo and Hu F. A multifaceted role of progranulin in regulating amyloid-beta dynamics and responses Life Sci Alliance. 2021 Jun 8;4(7):e202000874. doi: 10.26508/lsa.202000874.
Feng T, Lacrampe A, Hu F. Physiological and pathological functions of TMEM106B: a gene associated with brain aging and multiple brain disorders. Acta Neuropathol. 2021 Jan 1. doi: 10.1007/s00401-020-02246-3
Pang W, Hu F. Cellular and physiological functions of C9orf72 and implications for ALS/FTD. J Neurochem. 2020 Dec 1. doi: 10.1111/jnc.15255
Feng T, Mai S, Roscoe JM, Sheng RR, Ullah M, Zhang J, Katz II, Yu H, Xiong W, Hu F. Loss of TMEM106B and PGRN leads to severe lysosomal abnormalities and neurodegeneration in mice EMBO Rep. 2020 Aug 10:e50219. doi: 10.15252/embr.202050219.
Feng T, Sheng RR, Solé-Domènech S, Ullah M, Zhou X, Mendoza CS, Martinez Enriquez LC, Katz II, Paushter DH, Sullivan PM, Wu X, Maxfield FR, Hu F. A role of the frontotemporal lobar degeneration risk factor TMEM106B in myelination. Brain 2020 July https://doi.org/10.1093/brain/awaa154
Zhou X, Paushter D, Pagan M, Kim D, Nunez Santos M, Lieberman RL, Overkleeft HS, Sun Y, Smolka MB, Hu F. Progranulin deficiency results in reduced glucocerebrosidase activity. PLoS One. 2019 Jul 10;14(7):e0212382. doi: 10.1371/journal.pone.0212382.
Lan Y, Sullivan PM, Hu F. SMCR8 negatively regulates Akt and mTORC1 signaling to modulate lysosome biogenesis and tissue homeostasis. Autophagy 2019 Jan 29:1-15. doi: 10.1080/15548627.2019.1569914.
Paushter D, Huan D, Feng T, Hu F. The lysosomal function of progranulin, a guardian against neurodegeneration. Acta Neuropathol. 2018 Jul;136(1):1-17. doi: 10.1007/s00401-018-1861-8.
Zhonu X, Paushter D, Sullivan PM, Hu F. The Interaction between progranulin with sortilin and the lysosome. Methods in Molecular Biology 2018;1806:269-288. Andrew Bateman et al. (Eds): Progranulin, 978-1-4939-8557-9, 329208_1_En, (18) doi: 10.1007/978-1-4939-8559-3_18.
Zhou, X., Sullivan, P. M., Sun, L., & Hu, F. (2017). The interaction between progranulin and prosaposin is mediated by granulins and the linker region between saposin B and C. JNC: Journal of Neurochemistry. 143:236-243.
Zhou, X., Paushter, D. H., Feng, T., Sun, L., Reinheckel, T., & Hu, F. (2017). Lysosomal processing of progranulin. Molecular Neurodegeneration. 12:6.
Zhou, X., Paushter, D. H., Feng, T., Pardon, C. M., Mendoza, C. S., & Hu, F. (2017). Regulation of cathepsin D activity by the FTLD protein progranulin. Acta Neuropathologica. 134:151-153.
Zhou, X., Sun, L., Bracko, O., Choi, J. W., Jia, Y., Nana, A. L., Brady, O. A., Hernandez, Jean C. Cruz,, Nishimura, N., Seeley, W. W., & Hu, F. (2017). Impaired prosaposin lysosomal trafficking in frontotemporal lobar degeneration due to progranulin mutations. Nature Communications. 8:14.
Zhou, X., Sun, L., Brady, O. A., Murphy, K. A., & Hu, F. (2017). Elevated TMEM106B levels exaggerate lipofuscin accumulation and lysosomal dysfunction in aged mice with progranulin deficiency. Acta Neuropathologica Communications. 5:9.
Sullivan, P. M., Zhou, X., Robins, A., Paushter, D., Kim, D., Smolka, M., & Hu, F. (2016). The ALS/FTLD associated protein C9orf72 associates with SMCR8 and WDR41 to regulate the autophagy-lysosome pathway. Acta Neuropathologica Communications. 4.
Zhou, X., Sun, L., Oliveria, F., Qi, X., Brown, W. J., Smolka, M., Sun, Y., & Hu, F. (2015). Prosaposin facilitates sortilin independent lysosomal targeting of progranulin. JCB: The Journal of Cell Biology. 210:991.
Brady, O. A., Zheng, Y., Murphy, K., Huang, M., & Hu, F. (2013). The frontotemporal lobar degeneration risk factor, TMEM106B, regulates lysosomal morphology and function. Human Molecular Genetics. 22:685-695.
Zheng, Y., Brady, O., Meng, P., Mao, Y., & Hu, F. (2011). C-terminus of Progranulin interacts with the beta-propeller region of Sortilin to regulate Progranulin trafficking. PLOS One. 6:e21023.
Hu, F., Padukkavidana , T., Brady, O. A., Zheng, Y., & Strittmatter, S. (2010). Sortilin1-Mediated Endocytosis Determines Levels of the Fronto-Temporal Dementia Protein, Progranulin. Neuron. 68:654-67.
