NTUBST2023EN

The Laboratory of Cellular Membrane Remodeling, Lipid Homeostasis & Bioengineering is dedicated to understanding the molecular mechanisms that govern membrane dynamics, lipid metabolism, and cellular quality control. We also seek to translate fundamental biological discoveries into practical applications through the development of microbial engineering platforms and recombinant protein production technologies.

 

Membrane Remodeling & Quality Control Mechanisms

Cellular membrane systems undergo continuous remodeling and renewal to maintain organelle function and cellular homeostasis. To monitor damaged, misfolded, or obsolete membrane proteins, cells have evolved sophisticated quality control pathways, among which ubiquitination and autophagy play central roles. Our research aims to understand how these pathways coordinate the recognition, trafficking, and degradation of membrane proteins to preserve membrane integrity and organelle function.

 

We are particularly interested in how ubiquitin signaling selectively marks damaged or dysfunctional membrane proteins and directs them toward distinct degradation pathways, including endoplasmic reticulum-associated degradation (ERAD), endocytosis, and lysosomal/vacuolar degradation. We further investigate how ubiquitin-dependent signaling interfaces with membrane remodeling machinery to regulate membrane protein trafficking and determine protein fate across different organelles.

 

Another major focus of our research is the role of autophagy in membrane quality control. In addition to removing damaged organelles and protein aggregates, autophagy contributes to the turnover of membrane proteins and membrane structures. Because autophagosome biogenesis requires extensive membrane remodeling and membrane supply, membrane lipid composition, membrane curvature, and inter-organelle lipid trafficking profoundly influence autophagic activity. We seek to elucidate how membrane remodeling drives autophagosome formation and how ubiquitin-dependent quality control pathways cooperate with autophagy to maintain organelle and membrane homeostasis.

 

By studying the interplay between ubiquitin signaling, autophagy, and membrane dynamics, we aim to uncover how cells maintain membrane protein homeostasis and organelle function under conditions of metabolic stress, lipotoxicity, and other environmental challenges. Ultimately, our work seeks to provide mechanistic insights into diseases associated with defects in membrane quality control, including neurodegenerative disorders, metabolic diseases, and cancer.

 

 

Lipid Droplet Biology & Inter-Organelle Lipid Transport

Lipid droplets are the primary lipid storage organelles in eukaryotic cells. Beyond serving as reservoirs for neutral lipids, they play essential roles in energy metabolism, cellular signaling, and stress responses. We investigate the molecular mechanisms underlying lipid droplet biogenesis, maintenance, and degradation, and explore how these processes contribute to metabolic adaptation and cellular homeostasis.

We are also interested in membrane contact sites that mediate lipid exchange and communication between organelles. Our research focuses on understanding how lipids are transported among the endoplasmic reticulum, lipid droplets, mitochondria, vacuoles, and other organelles, and how defects in lipid trafficking contribute to organelle dysfunction and metabolic diseases.

 

 

Microbial Engineering & Biomanufacturing

Building upon our understanding of membrane trafficking, protein secretion, and cellular quality control mechanisms, we develop engineered fungal platforms for the efficient production of recombinant proteins and biopharmaceuticals.

 

Our research directions include:

• Engineering high-efficiency protein secretion strains through the optimization of protein folding pathways, secretory networks, and cellular metabolism.
• Constructing high-performance fungal cell factories for the production of vaccine antigens, peptide hormones, fusion proteins, and recombinant biotherapeutics.

 

We are also engaged in the development of fish viral vector technologies and molecular tools for aquaculture biotechnology. By establishing virus-host systems, cell lines, and plasmid-based platforms, we aim to create novel tools for vaccine development, gene expression, and functional studies.

 

Our research objectives include:

• Developing fish viral vectors for gene delivery applications.
• Establishing viral expression platforms for aquaculture vaccine development.

 

We utilize budding yeast Saccharomyces cerevisiae, methylotrophic yeast, and mammalian cell lines as models, employing cutting-edge techniques including advanced microscopy, lipidomics, and genetic manipulations to address these critical questions in the field. Our lab fosters 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. AR Yesian^#, MM Chalom^#, NH Knudsen, AL Hyde, J Personnaz, H Cho, YH Liou, KA. Starost, CW Lee, DY Tsai, HW Ho, JS Lin, J Li, FB Hu, AS Banks, and CH Lee* (2025). Preadipocyte IL-13/IL-13Rα1 signaling regulates beige adipogenesis through modulation of PPARγ activity. J. Clin. Investig., 135(11):e169152. (Citations ≥ 4, IF: 15.9, Q1)
2. 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 ≥ 21, IF: 17.694, Q1)
3. X Sui, K Wang, K Song, C Xu, J Song, CW Lee, M Liao, RV Farese Jr.*, and TC Walther* (2023). Mechanism of action for small molecule inhibitors of triacylglycerol synthesis. Nat. Commun., 14, 3100 (Citations ≥ 12, IF: 17.694, Q1)
4. 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 ≥ 84, IF: 12.777, Q1)
5. 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 ≥ 79, IF: 28.213, Q1)
6. 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 ≥ 18, IF: 17.694, Q1)
7. F Wilfling*^#, CW Lee^#, PS Erdmann*, and W Baumeister* (2021). Autophagy ENDing unproductive phase-separated endocytic protein deposits. Autophagy 17 (10), 3264-3265. (Citations ≥ 4, IF: 13.391, Q1)
8. 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 ≥ 115, IF: 17.970, Q1)
9. 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 ≥ 193, IF: 69.504, Q1)
10.  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 ≥ 121, IF: 28.213, Q1)
11.  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 ≥ 95, IF: 12.777, Q1)
12.  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 ≥ 23, IF: 5.486, Q1)
13.  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 ≥ 120, IF: 5.135, Q1)

 

 

Lab Alumni

 

林雨暘 (台灣農業化學會 114 年度研討會壁報比賽生化組優勝)

 

顏伶蓁 (台灣農業化學會 114 年度研討會壁報比賽生化組優勝)