Wen Lab

Research

My lab is dedicated to studying the intricate cell adhesion mechanisms that drive cardiovascular inflammation. Our aim is to better understand how the immune system works, especially focusing on neutrophils and other myeloid cells, in response to inflammation. The main focus is to use biosensors and transgenic mouse models to directly monitor immune cell recruitment and function during inflammation, infection and tissue injury in vitro and in vivo. We use state-of-the-art technology, including genome editing, multicolor flow cytometry, TIRF microscopy, intravital imaging, resonant-scanning confocal, and FRET microscopy to study inflammatory responses and signaling at molecular, cellular and whole organism levels.

Selected Publications

  1. Li W.*, Wen L.*, Rathod B., Gingras A.C., Ley K., Lee H.S. Kindlin2 enables EphB/ephrinB bi-directional signaling to support vascular development. Life Science Alliance. 2023. 6, (3). DOI 10.26508/lsa.202201800. [*, co-first authors]
  2. Wen L., Lyu Q., Ley K., Goult B. T. Structural basis of β2 integrin inside—out activation.Cells. 2022. 11 (19), 3039. doi: 10.3390/cells11193039.
  3. Wen L.,MarkiA., Wang Z., Makings J., Billitti M., Wang E., Kim K., Kiosses W.B., MikulskiZ., Ley K. A humanized β2 integrin knockin mouse reveals localized intra- and extra-vascular neutrophil integrin activation in vivo. Cell Reports. 2022. 39, 110876 (Featured with a cover image)
  4. Saigusa R, Roy P., Freuchet A., Gulati R., Ghosheh Y., Silas S., Suthahar S., Durant C.P., Hanna D. B., Kiosses W.B., Orecchioni M., Wen L., Wu R., et al.CD4 T cell response to MHC-II-restricted APOB epitope in human cardiovascular disease revealed by single cell transcriptomics and TCR reconstruction.Nat Cardiovasc Res. 2022. 1, 462–475.
  5. Wen L., Moser M., Ley K.Molecular mechanisms of leukocyte β2 integrin activation. Blood. 2022. 139 (24), 3480-3492.
  6. Orecchioni M., Kobiyama K., Winkels H., Ghosheh Y., McArdle S., Mikulski Z., Kiosses W.B., Fan Z., Wen L., Jung Y., et al. Olfactory receptor 2 in vascular macrophages drives atherosclerosis by NLRP3-dependent IL-1 production. Science. 2022. 375, 214-221.
  7. Fan Z., Pitmon E., Wen L., Miller J., Ehinger E., Herro R., Liu W., Chen J., Mikulski Z., Conrad D.J., et al. Bone Marrow Transplantation Rescues Monocyte Recruitment Defect and Improves Cystic Fibrosis in Mice. J Immunol. 2022. 208, 745-752.
  8. Jung Y., Wen L., Altman A., Ley K. CD45 pre-exclusion from the tips of T lymphocyte microvilli prior to antigen recognition. Nat Commun. 2021; 12, 3872.
  9. Wen L., Marki A., Roy P., McArdle S., Sun H., Fan Z., Gingras A., Ginsberg M., Ley K. Kindlin-3 recruitment to the plasma membrane precedes high affinity β2integrin and neutrophil arrest from rolling. Blood. 2021; 137 (1): 29–38.
  10. Wen L., Fan Z., Mikulski Z., and Ley K. Imaging of the immune system-towards a subcellular and molecular understanding. J Cell Sci. 2020;133(5).
  11. Wen L., Feil S., Wolters M., Thunemann M., Regler F., Schmidt K., Friebe A., Olbrich M., Langer H., Gawaz M., de Wit C., Feil R. A shear-dependent NO-cGMP-cGKI cascade in platelets acts as an auto-regulatory brake of thrombosis. Nat Commun. 2018, 9, 4301
  12. Wen L., Feil S., Feil R. cGMP signaling in platelets.In: Platelets, Haemostasis and Inflammation (eds. Zirlik, A., Bode, C. & Gawaz, M.). Springer, Cham. 2017, 231–252.
  13. Schmidt H., Peters S., Frank K., Wen L., Feil R., and Rathjen F.Dorsal root ganglion axon bifurcation tolerates increased cyclic GMP levels: the role of phosphodiesterase 2A and scavenger receptor Npr3. Eur J Neurosci. 2016, 44, 2991–3000.
  14. Shuhaibar L.C., Egbert J.R., Norris R., Lampe P., Nikolaev V.O., Thunemann M., Wen L., Feil R., Jaffe L.A. Intercellular signaling via cyclic GMP diffusion through gap junctions restarts meiosis in mouse ovarian follicles. Proc Natl Acad Sci USA: 2015, 112, 5527-32.
  15. Thunemann M.*, Wen L.*, Hillenbrand M., Vachaviolos A., Feil S., Ott T., Han X., Fukumura D., Jain R.K., Russwurm M., de Wit C., Feil R.Transgenic mice for cGMP imaging. Circ Res. 2013, 113, 365-371. [*, co-first authors]
  16. Fan G., Wen L., Li M., Li C., Luo B., Wang F., Zhou L., Liu L.Isolation of mouse mesenchymal stem cells with normal ploidy from bone marrows by reducing oxidative stress in combination with extracellular matrix. BMC Cell Biol. 2011, 12:P30.
  17. Wen L., Schwamborn J.C.Cellular reprogramming and its implications for therapeutic applications. Eur Pharm Rev. 2009,3, 36-40.