Dr. Xudong Wu received his bachelor’s degree of Biological Science from Fudan University in 2009. He then joined the Department of Molecular Biophysics and Biochemistry at Yale University for his Ph.D. and obtained his doctorate degree in 2014. His Ph.D. work mainly focused on dissecting the molecular mechanism of regulations of vesicular trafficking and phospholipid biogenesis and transport, under the mentorship of Dr. Karin Reinisch and in close collaboration with Dr. Pietro De Camilli. With the support from Jane Coffin Childs Memorial Fund for Medical Research, he did his postdoctoral training at Harvard Medical School under the mentorship of Dr. Tom Rapoport, working on understanding the mechanisms of protein homeostasis maintenance in the endoplasmic reticulum. Dr. Wu’s original work was published in Nature, Science, Nature Cell Biology, Developmental Cell, PNAS, and many other journals.

Neurodegenerative diseases such as AD, PD, and ALS are becoming an increasingly serious problems for our aging society. Unlike cancer, so far there is not even a single solution for treating those diseases and the mechanisms for the disease onset are still debatable.

Membrane-bound or membrane-less organelles are key features of eukaryotes, developed to compartmentalize the amazing diversity of biochemical reactions necessary for life. As life became more complex, these organelles gained specialized functions. Recently, a growing body of evidence highlighted that different organelles communicated and cooperated with each other via extensive membrane contact sites. During aging, organelles are under constant stresses, including stresses from misfolded proteins, calcium imbalance, lipotoxicity, oxidative stress, and so on. Although there exist multiple cellular mechanisms such as unfolded protein response (UPR) and mitophagy to handle stresses, failure to resolve stress eventually leads to cell death and is associated with numerous diseases from metabolic disorders to neurodegenerative diseases. 

Our lab will take an integrated approach including proteomics, biochemistry, molecular and cell biology, cell imaging, integrative structural biology to address key questions in pathways involved in maintaining organelle homeostasis, focusing on revealing the molecular mechanisms of those key targets associated with neurodegenerative diseases. The group will not only try to answer basic scientific questions, but also actively pursue translational research to create novel therapeutic modalities. Major directions will include but not limited to:

A. Molecular Mechanism of protein quality control systems at the membrane on different important organelles (such as ER and mitochondria).

B. Ubiquitin regulation of lipid metabolism and its transfer across different organelles.

C. Therapeutic exploration of membrane protein quality control systems and its potential in the interventions of neurodegenerative diseases.

To learn more about our research, please visit: https://xudongwu-lab.org/

(* co-first author; # corresponding author)

1. Feng P#, Wu X, Erramilli SK, Paulo JA, Knejski P, Gygi SP, Kossiakoff AA, Rapoport TA#. A peroxisomal ubiquitin ligase complex forms a retrotranslocation channel. Nature. 2022 Jul;607(7918):374-380. 

2. Wu X#, Rapoport TA#. Cryo-EM structure determination of small proteins by nanobody-binding scaffolds (Legobodies). PNAS. 2021 Oct 12;118(41): e2115001118.  

3. Wu X, Siggel M, Ovchinnikov S, Mi W, Svetlov V, Nudler E, Liao M, Hummer G, Rapoport TA#. Structural basis of ER-associated protein degradation mediated by the Hrd1 ubiquitin ligase complex. Science. 2020 Apr 24;368 (6489):eaaz2449. doi: 10.1126/science.aaz2449.

4. Wu X, Cabanos C, Rapoport TA#. Structure of the post-translational protein translocation machinery of the ER membrane. Nature. 2019 Feb;566 (7742):136-139.

5. Baskin JM*, Wu X*, Christiano R, Oh MS, Schauder CM, Gazzerro E, Messa M, Baldassari S, Assereto S, Biancheri R, Zara F, Minetti C, Raimondi A, Simons M, Walther TC, Reinisch KM#, De Camilli P#. The leukodystrophy protein FAM126A (hyccin) regulates PtdIns(4)P synthesis at the plasma membrane. Nat Cell Biol. 2016 Jan;18(1):132-8.

6. Wu X, Chi RJ, Baskin JM, Lucast L, Burd CG, De Camilli P, and Reinisch KM#. Structural insights into assembly and regulation of the plasma membrane phosphatidylinositol 4-kinase complex. Dev Cell. 2014 Jan 13;28(1):19-29.

7. Schauder CM, Wu X, Saheki Y, Narayanaswamy P, Torta F, Wenk MR, De Camilli P#, Reinisch KM#. Structure of a lipid-bound Extended-Synaptotagmin indicates a role in lipid transfer. Nature. 2014 Jun 26;510(7506):552-5.

8. Wu X, Bradley MJ, Cai Y, Kümmel D, De La Cruz EM, Barr FA, Reinisch KM#. Insights regarding guanine nucleotide exchange from the structure of a DENN-domain protein complexed with its Rab GTPase substrate. PNAS. 2011 Nov 15; 108 (46):18672-7.

9. Wu X, Wu D, Lu Z, Chen W, Hu X, Ding Y#. A novel method for high-level production of TEV protease by superfolder GFP tag. J Biomed Biotechnol. 2009; 2009:591923. 

10. Wu X, Rapoport TA#. Translocation of proteins through a distorted lipid bilayer. Trends Cell Biol. 2021 Jan 30;S0962-8924 (21) 00006-4. (Review)

11. Wu X, Rapoport TA#. Mechanistic insights into ER-associated protein degradation. Curr Opin Cell Biol. 2018 Aug; 53:22-28. (Review)

The full list of publications can be found at:

https://scholar.google.com/citations?user=_U17aV8AAAAJ&hl=en

Email: wuxudong@westlake.edu.cn

The lab just launched in September 2022. We are looking for brilliant minds like YOU to join our interdisciplinary lab to find a way to treat neurodegenerative diseases. Students, research assistants and postdocs with interests and expertise in biochemistry, molecular and cell biology, cell imaging, protein engineering or related fields are welcome to apply. Both domestic and international talents are encouraged to join.

For more information, please visit: https://xudongwu-lab.org/join-us/