Michael Hanna
In 1955, an organelle filled with lytic enzymes thought to be capable of destroying everything within a mammalian cell was discovered. Over the next year, some of the first electron microscopy images of cells would reveal this organelle, named the Lysosome, to be small (~300 nm) membrane-bound compartments. The possibility that lysosomes might become ruptured under certain conditions and kill or injure their host-cells as a result, was immediately considered (as told by Christian de Duve, the scientist who discovered the lysosome). Today, lysosomes are regarded as critical signaling hubs that control cellular metabolism and whose dysfunction is increasingly implicated in neurodegenerative disease. As the degradative endpoint of the endocytic and autophagic pathways, lysosomes are particularly susceptible to damage–a biological problem that has been on the mind of scientists for seven decades.
Over the years, numerous endogenous and exogenous factors have been found to damage or even rupture lysosomes. These include lysosomotropic compounds (e.g. chloroquine, an antimalarial drug), lipid peroxides, pathogens, and even ageing. Such damage disrupts lysosome function and any escape of their lumenal content into the cytosol can damage other organelles and activate cell death pathways. In just the past decade, cellular mechanisms thought to sense and possibly limit or repair damage to lysosomes have been revealed. This amazing advance has led to a renaissance in the study of lysosomes.
The Hanna lab aims to define the molecular pathways that detect, limit, and repair damage to lysosomes using a combination of cell biological and biochemical approaches. We use live-cell fluorescence microscopy to quantitatively measure organelle health and dynamics in mammalian cells. Furthermore, we leverage techniques to immunoisolate whole lysosomes for proteomic and lipidomic characterization. The lab will open January 1st, 2026, on the first floor of the Huck Life Sciences Building. We are looking for enthusiastic and highly motivated new members at all levels to join our work on high-impact projects designed to establish momentum in the lab!
A bit about me
I received my PhD in Molecular and Cellular Pharmacology from the University of Wisconsin-Madison, where I uncovered new mechanisms to control the cellular machinery responsible for transporting proteins and membranes within mammalian cells. I’m now finishing up my postdoc in the Department of Neuroscience at Yale University, where my research has revealed new ways in which cells support organelle health and resilience. Outside of the lab, I like to bake (mostly cookies), read fantasy books, and listen to baseball games.
Selected publications
Hanna, M.G., Rodriguez Cruz, H.O., Fujise. K, Li, Z, Monetti, M, De Camilli, P. (2024). Bridge-like lipid transfer protein 3 (BLTP3A) is associated with membranes of the late endocytic pathway and is an effector of CASM. bioRxiv DOI: 10.1101/2024.09.28.615015
Hanna, M.G.*, Guillén-Samander, A*, De Camilli, P. RBG-motif bridge-like lipid transport proteins: structure, functions, and open questions. (2023). Annual Review of Cell and Developmental Biology, 39 Review. PMID: 37406299. DOI: 10.1146/annurev-cellbio-120420-014634
Hanna, M.G.*, Suen, P.H.*, Wu, Y., Reinisch, K.M., De Camilli, P. (2022). SHIP164 is a chorein motif lipid transfer protein that controls endosome-Golgi membrane traffic. Journal of Cell Biology, 6;221(6) PMID: 35499567. DOI: 10.1083/jcb.202111018
Hanna, M.G., Block, S.D., Frankel, E.B., Hou, F., Johnson, A.J., Yuan, L., Knight, G., Moresco, J.J., Yates, J.R., Ashton, R., Schekman, R., Ton, Y., Audhya, A. (2017). TFG facilitates outer coat disassembly on COPII transport carriers to promote fusion with ER‑Golgi intermediate compartments. PNAS, 114(37):E7707‑E7716. PMID: 28851831. DOI: 10.1073/pnas.1709120114
Hanna, M.G., Mela, I, Wang, L, Henderson, R.M., Chapman, E.R., Edwardson, M.J., Audhya, A. (2015). Sar1 GTPase Activity is Regulated by Membrane Curvature. Journal of Biological Chemistry, 291(3):1014‑27. PMID: 26546679. DOI: 10.1074/jbc.M115.672287
*Co-first author