#  VWF 

 



One new area of research in the lab is von Willebrand factor and mutations that cause the important bleeding diathesis, von Willebrand disease. We are pursuing single molecule experiments, functional assays, electron microscopy, and crystallography to understand the complex mechanobiology of VWF, which is the largest soluble protein in the body and functions as a shear sensor in the vasculature to arrest arteriolar bleeding. The conformation of VWF, its binding to ligands on the vessel wall and on platelets, and its cleavage by ADAMTS13 are regulated by shear.



 

##  Recent Publications 

 



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### 2025

Watson, S. M., Harvey, E. P., Pishesha, N., Ploegh, H. L. &amp; Springer, T. A. [Nanobodies targeting EGFR provide insight into conformations stabilized by glioblastoma mutations.](/publication/nanobodies-targeting-egfr-provide-insight-conformations-stabilized-glioblastoma) *The Journal of biological chemistry* 110374 (2025) doi:10.1016/j.jbc.2025.110374.



 

 

Watson, S. M., Harvey, E. P., Pishesha, N., Ploegh, H. L. &amp; Springer, T. A. [Nanobodies targeting EGFR provide insight into conformations stabilized by glioblastoma mutations.](/publication/nanobodies-targeting-egfr-provide-insight-conformations-stabilized-glioblastoma) *The Journal of biological chemistry* 110374 (2025) doi:10.1016/j.jbc.2025.110374.



 

 

 

- add\_circle do\_not\_disturb\_on Abstract
- [ picture\_as\_pdf{Watson, 2025, 39438}.pdf](/sites/g/files/omnuum3646/files/2025-07/%7BWatson%2C%202025%2C%2039438%7D.pdf)
 
Oncogenic mutations in the epidermal growth factor receptor (EGFR) promote tumorigenesis by stabilizing active or pre-active receptor conformations. Most EGFR-driven cancers are characterized by kinase domain mutations that directly activate the receptor...



 

 

- [ picture\_as\_pdf{Watson, 2025, 39438}.pdf](/sites/g/files/omnuum3646/files/2025-07/%7BWatson%2C%202025%2C%2039438%7D.pdf)
 
 

Wang, X. *et al.* [De novo design of integrin α5β1 modulating proteins to enhance biomaterial properties](/publication/de-novo-design-integrin-a5b1-modulating-proteins-enhance-biomaterial-properties). *Adv Mater* (2025) doi:10.1002/adma.202500872.



 

 

Wang, X. *et al.* [De novo design of integrin α5β1 modulating proteins to enhance biomaterial properties](/publication/de-novo-design-integrin-a5b1-modulating-proteins-enhance-biomaterial-properties). *Adv Mater* (2025) doi:10.1002/adma.202500872.



 

 

 

- add\_circle do\_not\_disturb\_on Abstract
- [ descriptionPublisher's Version](https://pubmed.ncbi.nlm.nih.gov/40489013/)
- [ picture\_as\_pdf{Wang, 2025, 39004}.pdf](/sites/g/files/omnuum3646/files/2025-11/%7BWang%2C%202025%2C%2039004%7D.pdf)
 
Integrin alpha5beta1 is crucial for cell attachment and migration in development and tissue regeneration, and alpha5beta1 binding proteins can have considerable utility in regenerative medicine and next-generation therapeutics. We use computational...



 

 

- [ descriptionPublisher's Version](https://pubmed.ncbi.nlm.nih.gov/40489013/)
- [ picture\_as\_pdf{Wang, 2025, 39004}.pdf](/sites/g/files/omnuum3646/files/2025-11/%7BWang%2C%202025%2C%2039004%7D.pdf)
 
 

 



### 2024

Li, J. *et al.* [Ligand binding initiates single-molecule integrin conformational activation](/publications/ligand-binding-initiates-single-molecule-integrin-conformational-activation). *Cell* **187**, 2990–3005.e17 (2024).



 

 

Li, J. *et al.* [Ligand binding initiates single-molecule integrin conformational activation](/publications/ligand-binding-initiates-single-molecule-integrin-conformational-activation). *Cell* **187**, 2990–3005.e17 (2024).



 

 

 

- add\_circle do\_not\_disturb\_on Abstract
- [ picture\_as\_pdfli\_2024\_38998.pdf](/sites/g/files/omnuum3646/files/li_2024_38998.pdf)
- [ picture\_as\_pdfli\_2024\_38998\_supp.pdf](/sites/g/files/omnuum3646/files/li_2024_38998_supp.pdf)
 
 Integrins link the extracellular environment to the actin cytoskeleton in cell migration and adhesiveness. Rapid coordination between events outside and inside the cell is essential. Single-molecule fluorescence dynamics show that ligand binding to the... 

 

 

- [ picture\_as\_pdfli\_2024\_38998.pdf](/sites/g/files/omnuum3646/files/li_2024_38998.pdf)
- [ picture\_as\_pdfli\_2024\_38998\_supp.pdf](/sites/g/files/omnuum3646/files/li_2024_38998_supp.pdf)
 
 

 



### 2023

Roy, A. *et al.* [De novo design of highly selective miniprotein inhibitors of integrins αvβ6 and αvβ8](/publications/de-novo-design-highly-selective-miniprotein-inhibitors-integrins-%CE%B1v%CE%B26-and-%CE%B1v%CE%B28). *Nat Commun* **14**, 5660 (2023).



 

 

Roy, A. *et al.* [De novo design of highly selective miniprotein inhibitors of integrins αvβ6 and αvβ8](/publications/de-novo-design-highly-selective-miniprotein-inhibitors-integrins-%CE%B1v%CE%B26-and-%CE%B1v%CE%B28). *Nat Commun* **14**, 5660 (2023).



 

 

 

- add\_circle do\_not\_disturb\_on Abstract
- [ picture\_as\_pdfroy-2023-37949.pdf](/sites/g/files/omnuum3646/files/tas/files/roy-2023-37949.pdf)
 
 The RGD (Arg-Gly-Asp)-binding integrins αvβ6 and αvβ8 are clinically validated cancer and fibrosis targets of considerable therapeutic importance. Compounds that can discriminate between homologous αvβ6 and αvβ8 and other RGD integrins, stabilize specific... 

 

 

- [ picture\_as\_pdfroy-2023-37949.pdf](/sites/g/files/omnuum3646/files/tas/files/roy-2023-37949.pdf)
 
 

 



### 2022

Jo, M. H. *et al.* [Single-molecule characterization of subtype-specific β1 integrin mechanics](/publications/single-molecule-characterization-subtype-specific-%CE%B21-integrin-mechanics). *Nat Commun* **13**, 7471 (2022).



 

 

Jo, M. H. *et al.* [Single-molecule characterization of subtype-specific β1 integrin mechanics](/publications/single-molecule-characterization-subtype-specific-%CE%B21-integrin-mechanics). *Nat Commun* **13**, 7471 (2022).



 

 

 

- add\_circle do\_not\_disturb\_on Abstract
- [ picture\_as\_pdfjo\_2022\_37809.pdf](/sites/g/files/omnuum3646/files/tas/files/jo_2022_37809.pdf)
 
 Although integrins are known to be mechanosensitive and to possess many subtypes that have distinct physiological roles, single molecule studies of force exertion have thus far been limited to RGD-binding integrins. Here, we show that integrin α4β1 and... 

 

 

- [ picture\_as\_pdfjo\_2022\_37809.pdf](/sites/g/files/omnuum3646/files/tas/files/jo_2022_37809.pdf)
 
 

Lin, F.-Y. *et al.* [A general chemical principle for creating closure-stabilizing integrin inhibitors](/publications/general-chemical-principle-creating-closure-stabilizing-integrin-inhibitors). *Cell* **185**, 3533–3550.e27 (2022).



 

 

Lin, F.-Y. *et al.* [A general chemical principle for creating closure-stabilizing integrin inhibitors](/publications/general-chemical-principle-creating-closure-stabilizing-integrin-inhibitors). *Cell* **185**, 3533–3550.e27 (2022).



 

 

 

- add\_circle do\_not\_disturb\_on Abstract
- [ picture\_as\_pdflin\_2022\_38059.pdf](/sites/g/files/omnuum3646/files/tas/files/lin_2022_38059.pdf)
 
 Integrins are validated drug targets with six approved therapeutics. However, small-molecule inhibitors to three integrins failed in late-stage clinical trials for chronic indications. Such unfavorable outcomes may in part be caused by partial agonism, i... 

 

 

- [ picture\_as\_pdflin\_2022\_38059.pdf](/sites/g/files/omnuum3646/files/tas/files/lin_2022_38059.pdf)
 
 

 



 

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##  VWF Researchers 

 



  [### Bhaskar Paidimuddala, Ph.D.

 ](/people/bhaskar-paidimuddala-phd)Postdoctoral Research Fellow

 

 

 

      ![paidimuddala](/sites/g/files/omnuum3646/files/styles/hwp_4_5__690x865/public/tas/files/paidimuddala.jpg?itok=xMr2HZ_w) 

 

 

 

   [### Hongxia Fu, Ph.D.

 ](/people/hongxia-fu-phd) <hfu@uw.edu>Assistant Professor, University of Washington

 

 

 

      ![fu-hongxia.jpg](/sites/g/files/omnuum3646/files/styles/hwp_4_5__690x865/public/tas/files/fu-hongxia.jpg?itok=zI7HRRvf) 

 

 

 

   [### Jordan Anderson, PhD

 ](/people/jordan-anderson-phd)Senior Scientist, Tectonic Tx

 

 

 

 person 

 

   [### Klaus Bonazza

 ](/people/klaus-bonazza)Postdoctoral Research Fellow

 

 

 

      ![bonazza-klaus.jpg](/sites/g/files/omnuum3646/files/styles/hwp_4_5__690x865/public/tas/files/bonazza-klaus.jpg?itok=JooVa4wT) 

 

 

 

   [### Uriel López-Sánchez, PhD

 ](/people/uriel-l%C3%B3pez-s%C3%A1nchez-phd)Postdoctoral Research Fellow 

Boston Children's Hospital, Harvard Medical School

 

 

 

      ![uriel headshot](/sites/g/files/omnuum3646/files/styles/hwp_4_5__690x865/public/tas/files/screen_shot_2022-09-14_at_8.54.46_am.png?itok=U685NUyf)