NTUBST2023EN

The Laboratory of Cellular Membrane Remodeling and Lipid Homeostasis is dedicated to investigating the intricate processes that govern cellular membrane dynamics and lipid composition regulation, with a particular emphasis on the interplay between autophagy, lipid storage and mobilization, and quality control mechanisms.

 

Autophagy is a degradative pathway that encompasses the selective clearance and recycling of superfluous or defective intracellular components to maintain cellular homeostasis. This process involves extensive membrane remodeling, giving rise to autophagosomes—double-membrane vesicles that sequester cytosolic cargo and subsequently fuse with a degradative compartment, i.e. the lysosome or vacuole, for turnover. We study the interconnections between autophagy, membrane remodeling, and lipid metabolism to understand how lipid molecules and membrane dynamics contribute to the regulation and functionality of autophagy. By gaining insights into these underlying mechanisms, we strive to uncover the role of autophagy in maintaining cellular health, as well as its implications in diseases associated with compromised autophagic processes, including cancers and neurodegenerative diseases.

 

Another key research focus in our lab is lipid storage and mobilization. We investigate the molecular basis that controls the storage and release of lipids in cellular compartments, such as lipid droplets. Lipid droplets are specialized organelles that store lipids, including triglyceride and steryl esters, in a neutral form. Our goal is to understand how lipid droplets serve as dynamic hubs for lipid metabolism, energy storage, and signaling pathways. In addition, we study how lipids traffic within cells, particularly at inter-organelle membrane contact sites, and explore the role of lipid dysregulation in metabolic disorders.

 

Quality control mechanisms are of paramount importance for safeguarding membrane integrity and preventing the accumulation of damaged or misfolded proteins on the membrane. Our lab investigates the role of lipid membranes and lipid-protein interactions in quality control pathways, such as ER-associated degradation (ERAD) and the unfolded protein response (UPR). We aim to decipher how lipid composition, membrane dynamics and lipid metabolism contribute to the regulation and efficiency of quality control processes, especially under lipotoxic conditions or in other metabolic contexts.

 

We utilize budding yeast Saccharomyces cerevisiae and mammalian cell lines as models, combined with cutting-edge techniques including advanced microscopy, lipidomics, and genetic manipulations to address these important questions in the field. We foster a collaborative environment where students work mutually and join forces internationally with research groups from Germany (Wilfling Lab at MPIBP) and United States (Sui Lab at Texas A&M University). This collaboration offers students the prospect of exciting international research experiences. We warmly welcome students interested in studying abroad to join our lab and become part of these enriching opportunities!

 

# Equal contribution

* Corresponding author

1. K Wang, CW Lee, X Sui, S Kim, S Wang, AB Higgs, AJ Baublis, GA Voth, M Liao*, TC Walther*, and RV Farese Jr.* (2023). The structure of phosphatidylinositol remodeling MBOAT7 reveals its catalytic mechanism and enables inhibitor identification. Nat. Commun., 14, 3533 (Citations ≥ 3, IF: 17.694, 6/204=2.9% in Biochemistry, Genetics and Molecular Biology (all) (Q1)) 
2. X Sui, K Wang, K Song, C Xu, J Song, CW Lee, M Liao, RV Farese Jr.*, and TC Walter* (2023). Mechanism of action for small molecule inhibitors of triacylglycerol synthesis. Nat. Commun., 14, 3100 (IF: 17.694, 6/204=2.9% in Biochemistry, Genetics and Molecular Biology (all) (Q1)) 
3. A Bieber^#, C Capitanio^#, PS Erdmann*, F Fiedler, F Beck, CW Lee, D Li, G Hummer, BA Schulman*, W Baumeister*, and F Wilfling* (2022). In situ structural analysis reveals membrane shape transitions during autophagosome formation. Proc. Natl. Acad. Sci. USA. 119 (39), e2209823119 (Citations ≥ 19, IF: 12.777, 4/110=3.6% in Multidisciplinary (Q1))
4. J Song, A Mizrak, CW Lee, M Cicconet, ZW Lai, WC Tang, CH Lu, SE Mohr, RV Farese Jr.*, and TC Walther* (2022). Identification of two pathways mediating protein targeting from ER to lipid droplets. Nat. Cell Biol. 24, 1364–1377. (Citations ≥ 13, IF: 28.213, 6/276=2.2% in Cell Biology (Q1))
5. S Qiao, CW Lee^#, D Sherpa^#, J Chrustowicz^#, J Cheng, M Duennebacke, B Steigenberger, O Karayel, DT Vu, SV Gronau, M Mann, F Wilfling, and BA  Schulman* (2022). Cryo-EM structures of Gid12-bound GID E3 reveal steric blockade as a mechanism inhibiting substrate ubiquitylation. Nat. Commun. 13 (1), 3041. (Citations ≥ 3, IF: 17.694, 6/204=2.9% in Biochemistry, Genetics and Molecular Biology (all) (Q1))
6. F Wilfling*^#, CW Lee^#, PS Erdmann*, and W Baumeister* (2021). Autophagy ENDing unproductive phase-separated endocytic protein deposits. Autophagy 17 (10), 3264-3265. (IF: 13.391, 21/279=7.5% in Cell Biology (Q1))
7. F Wilfling*^#, CW Lee^#, PS Erdmann*, Y Zheng, D Sherpa, S Jentsch, B Pfander, BA Schulman, and W Baumeister* (2020). A selective autophagy pathway for phase-separated endocytic protein deposits. Mol. Cell 80 (5), 764–778. (Citations ≥ 70, IF: 17.970, 10/274=3.6% in Cell Biology (Q1))
8. M Allegretti^#, CE Zimmerli^#, V Rantos, F Wilfling, P Ronchi, HKH Fung, CW Lee, W Hagen, B Turonova, K Karius, X Zhang, C Müller, Y Schwab, J Mahamid, B Pfander*, J Kosinski*, and M Beck* (2020). In-cell architecture of the nuclear pore and snapshots of its turnover. Nature 586, 796–800. (Citations ≥ 114, IF: 69.504, 1/110=0.9% in Multidisciplinary (Q1))
9. CW Lee^#, F Wilfling^#, P Ronchi, M Allegretti, S Mosalaganti, S Jentsch, M Beck*, and B Pfander* (2020). Selective autophagy degrades nuclear pore complexes. Nat. Cell Biol. 22 (2), 159-166. (Citations ≥ 69, IF: 28.213, 6/276=2.2% in Cell Biology (Q1))
10. S. Albert, W Wietrzynski^#, CW Lee^#, M Schaffer^#, F Beck, JM Schuller, PA Salomé, JM Plitzko, W Baumeister*, and BD Engel* (2019). Direct visualization of degradation microcompartments at the ER membrane. Proc. Natl. Acad. Sci. USA. 117 (2), 1069-1080. (Citations ≥ 63, IF: 12.777, 4/110=3.6% in Multidisciplinary (Q1))
11. CW Lee, FC Yang, HY Chang, H Chou, BCM Tan, and SC Lee* (2014). Interaction between salt-inducible kinase 2 and protein phosphatase 2A regulates the activity of calcium/calmodulin-dependent protein kinase I and protein phosphatase methylesterase-1. J. Biol. Chem. 289 (30), 21108-21119. (Citations ≥ 15, IF: 5.486, 68/415=16.4% in Biochemistry (Q1))
12. CM Wen*, CW Lee, CS Wang, YH Cheng, and HY Huang (2008). Development of two cell lines from Epinephelus coioides brain tissue for characterization of betanodavirus and megalocytivirus infectivity and propagation. Aquaculture 278 (1-4), 14-21. (Citations ≥ 110, IF: 5.135, 19/224=8.4% in Aquatic Science (Q1))