# TGF-β TGF-β signaling regulates development, wound healing, immune responses, and tumour-cell growth and inhibition. Latent TGF-β and receptors for active TGF-β are ubiquitous; it is activation of TGF-β in the extracellular space that limits activity. Recently, we have determined a structure of latent TGF-β1 that reveals how the latency associated peptide (LAP), a 250 residue prodomain, shields the 110 residue growth factor and participates in its activation through interactions with αV integrins and latent TGF-β binding proteins (LTBPs). We also have studied how a different cell surface protein called GARP becomes disulfide linked to latent TGF-β, and presents it for activation by integrins αVβ6 and αVβ8 that are expressed on immune cells, and bind to an RGD motif in LAP. We believe that yet another cell surface molecule that presents latent TGF-β remains to be discovered. Furthermore, we are interested in understanding how other TGF-βs are activated, particularly TGF-β2, which lacks the RGD integrin-binding motif in its LAP sequence. A wide range of projects, all the way from knockout mice to structure determination, are in the offing. ## Recent Publications Download 56 citations download- [BibTeX](/bibcite/export?pager_style=standard_pager&number_of_items=6&sort_field=bibcite_year--desc&taxonomy_filters=&&&format=bibtex) - [EndNote X3 XML](/bibcite/export?pager_style=standard_pager&number_of_items=6&sort_field=bibcite_year--desc&taxonomy_filters=&&&format=endnote8) - [EndNote 7 XML](/bibcite/export?pager_style=standard_pager&number_of_items=6&sort_field=bibcite_year--desc&taxonomy_filters=&&&format=endnote7) - [Endnote tagged](/bibcite/export?pager_style=standard_pager&number_of_items=6&sort_field=bibcite_year--desc&taxonomy_filters=&&&format=tagged) - [Marc](/bibcite/export?pager_style=standard_pager&number_of_items=6&sort_field=bibcite_year--desc&taxonomy_filters=&&&format=marc) - [PubMedId](/bibcite/export?pager_style=standard_pager&number_of_items=6&sort_field=bibcite_year--desc&taxonomy_filters=&&&format=pubmed_id) - [RIS](/bibcite/export?pager_style=standard_pager&number_of_items=6&sort_field=bibcite_year--desc&taxonomy_filters=&&&format=ris) ### 2025 Watson, S. M., Harvey, E. P., Pishesha, N., Ploegh, H. L. & 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. & 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) - Previous page chevron\_left - [1](?page=0 "Current page") - [2](?page=1 "Go to page 2") - [3](?page=2 "Go to page 3") - [4](?page=3 "Go to page 4") - [5](?page=4 "Go to page 5") - [6](?page=5 "Go to page 6") - [7](?page=6 "Go to page 7") - [8](?page=7 "Go to page 8") - [9](?page=8 "Go to page 9") - [ Last page 10 ](?page=9 "Go to last page") - [ Next page chevron\_right ](?page=1 "Go to next page") [ More arrow\_circle\_right ](/publications)