Wen lab has two different, but interconnected research focuses. One focus of the Wen lab is aimed at understanding the signaling pathways that govern proper B and T cell activation and communications and how aberrant signaling in T and B cells will lead to human diseases. The lab has studied the mechanisms by which molecules in antigen receptor signaling pathways such as: phospholipase C gamma (PLCg), B-cell lymphoma 10 (Bcl10), and molecules in cytokine signaling pathways, including Grb2-associated binding (Gab) proteins, control and modulate T and B cell development and activation and how aberrant functions of these molecules lead to lymphopenia and autoimmunity.

Another major focus of the Wen lab is understanding the interplay between immune systems and coagulation systems in healthy and disease states. Currently, the lab is studying how antibodies regulate the function of platelets and other cells involved in the coagulation system and the prevalence, ontogeny, and activation of the host B cells that make such antibodies in healthy people and patients with heparin-induced thrombocytopenia and thrombosis (HIT) and COVID-19. Studies will be performed in both human and mouse systems using techniques of biochemistry, cell biology, molecular biology, and bioinformatics with the goal of understanding the molecular pathogenesis underlying antibody mediated thrombotic complications in HIT and COVID-19 and developing new diagnostic and therapeutic tools for these conditions. 

• R01 HL148120 (PI), "Molecular Basis of Humoral Immune Response in Heparin-Induced Thrombocytopenia" 2019-2023
• R01 AI083636-06 (PI: Salomon), "Phosphoproteomic Analysis of Feedback Networks in T Cell Signaling" 2017-2022 
• R01 HL130724 (PI: Wang), "B Cell Responses in Heparin-Induced Thrombocytopenia" 2021-2025
• Ziegler Family Innovation Award (PI), "Development of RBD-specific Platelet-activating Antibodies in COVID-19 Patients" 2021-2022
• ACTIV-4 Mechanistic Studies (PI: Kreuziger) "Antibody Mediated Thromboinflammation in COVID-19" 2021-2022

Guoping Fu
Sr. Research Associate 

Yongwei Zheng
Research Scientist

Click here for a complete list of publications.

Selected Publications

1. Wen R*, Chen Y, Fu G, Schuman J, Yang C, Cleveland JL and Wang D*. An essential role of phospholipase Cg2 in early B cell development and Myc-mediated lymphomagenesis. Mol Cell Biol. 2006, 26:9364-9376. *equal senior authorship, PMCID: PMC1698523
2. Wang D, You Y, Lin P, Xue L, Morris SW, Zeng H, Wen R, Lin X. Bcl10 plays a critical role in NF-κB activation induced by G protein-coupled receptors. Proc Natl Acad Sci U S A. 2007, 104:145-150. PMCID: PMC1765424
3. Chen Y, Pappu B, Zeng H, Xue L, Morris SW, Lin X, Wen R,* Wang D.* Bcl10 is essential for FcεR-mediated degranulation and IL-6 production in mast cells. J Immunol. 2007, 178: 49-57. *equal senior authorship. PMID: 17182539
4. Misra RS, Russell JQ, Koenig A, Hinshaw-Makepeace JA, Wen R, Wang D, Huo H, Littman DR, Ferch U, Ruland J, Thome M, Budd RC. Caspase-8 and c-FLIPL associate in lipid rafts with NF-κB adaptors during T cell activation. J Biol Chem. 2007, 282: 19365-19374. PMID: 17462996
5. Zeng H, Di L, Fu G, Cheng Y, Gao X, Xu L, Lin X, Wen R. Phosphorylation of Bcl10 negatively regulates T cell receptor-mediated NF-κB activation. Mol Cell Biol. 2007, 27: 5235-5245. PMID: 17502353
6. Dai X, Chen Y, Di L, Podd A, Li G, Bunting KD, Hennighausen L, Wen R, Wang D. Stat5 is essential for early B cell development but not for B cell maturation and function. J Immunol. 2007; 179:1068-1079
7. Bai L, Chen Y, He Y, Dai X, Lin X, Wen R, and Wang D. Phospholipase Cg2 contributes to light chain gene activation and receptor editing. Mol Cell Biol. 2007 27: 5957-5967. PMCID: PMC1952164.
8. Malarkannan S, Regunathan J, Chu H, Chen Y, Zeng H, Kutlesa S, Wen R, Wang D. Bcl10 plays a divergent role in NK cell-mediated cytotoxicity and cytokine generation. J. Immunol. 2007, 15: 3752-3762. PMID: 17785812
9. Chen Y, Yu M, Podd A, Wen R, Chrzanowska-Wodnicka M, White GC, Wang D. A critical role of Rap1b in B cell trafficking and marginal zone B cell development. Blood. 2008; 111:4627-4636. PMCID: PMC2343596
10. Zeng H, Chen Y, Yu M, Xue L, Gao X, Morris SW, Wang D, Wen R. T cell receptor-mediated activation of CD4⁺CD44^hi T cells bypasses Bcl10: an implication of differential NF-κB dependence of naïve and memory T cells during T cell receptor-mediated responses. J Biol Chem. 2008, 5:24392-24399. PMCID: PMC2528987
11. Chen Y, Wang X, Di L, Fu G, Chen Y, Bai L, Liu J, Feng X, McDonald JM, Michalek S, He Y, Yu M, Fu YX, Wen R, Wu H, Wang D. Phospholipase Cγ2 mediates RANKL-stimulated lymph-node organogenesis and osteoclastogenesis. J Biol Chem. 2008, 283:29593-29601. PMCID: PMC2570883. 
12. Schuman J, Chen Y, Podd A, Liu H, Wen R, Chen ZJ, Wang D. A critical role of TAK1 in B cell receptor-mediated NF-κB activation. Blood. 2009, 113:4566-4574. PMCID: PMC2680363.
13. Jana S, Jailwala P, Haribhai D, Waukau J, Glisic S, Grossman W, Mishra M, Wen R, Wang D, Williams CB, Ghosh S. The role of NF-κB and Smad3 in TGF-beta-mediated Foxp3 expression. Eur J Immunol. 2009, 39:2571-83. PMID: 19701891
14. Fu G, Chen Y, Yu M, Podd A, Di L, He Y, Williams CB, North PE, Wang D, Wen R. Phospholipase Cγ1 is essential for T-cell development, activation and tolerance. J Exp Med. 2010, 207:309-318. PMCID: PMC2822604
15. Wuerzberger-Davis S, Chen Y, Yang DT, Bates P, Ladell NC, Yu M, Podd A, Zeng H, Wen R, Wang D, Miyamoto S. Nuclear export of the NF-κB inhibitor IκBα is required for proper B cell and secondary lymphoid tissue formation. Immunity. 2011, 34:188-200. PMCID: PMC3111750
16. Chen Y, Yu M, Dai X, Zogg M, Wen R, Weiler H, Wang D. Critical role for Gimap5 in the survival of mouse hematopoietic stem and progenitor cells. J Exp Med. 2011, 208:923-935. PMCID: PMC3092340
17. Fu G, Chen Y, Schuman J, Wang D, Wen R. Phospholipase Cγ2 Plays a Role in TCR Signal Transduction and T Cell Selection. J. Immunol. 2012, 189: 2326-2332, PMID: 22837484
18. Nurieva RI, Podd A, Chen Y, Alekseev AM, Yu M, Qi X, Huang H, Wen R, Wang J, Li HS, Watowich SS, Qi H, Dong C, and Wang D.  STAT5 protein negatively regulates T follicular helper cell generation and function. J. Biol. Chem. 2012, 287:11234-11239, PMID: 22318729
19. Yu M, Chen Y, He Y, Podd A, Fu G, Wright JA, Kleiman E, Khan WN, Wen R, Wang D. Critical role of B cell lymphoma 10 in BAFF-regulated NF-κB activation and survival of anergic B cells. J. Immunol. 2012, 189:5185-5193, PMID: 23087406
20. Zheng Y, Yu M, Podd A, Yuan L, Newman DK, Wen R, Arepally G, Wang D. Critical role for mouse marginal zone B cells in PF4/heparin antibody production. Blood. 2013, 121:3484-3492. PMID: 23460609
21. Zheng Y, Wang AW, Yu M, Padmanabhan A, Tourdot BE, Newman DK, White GC, Aster RH, Wen R, Wang D. B-cell tolerance regulates production of antibodies causing heparin-induced thrombocytopenia. Blood. 2014 123:931-934. PMID: 24357731; PMCID: PMC3916881
22. He XP, Wen R, McNamara JO. Impairment of kindling development in phospholipase Cγ1 heterozygous mice. Epilepsia. 2014, 55:456-463, PMID: 24502564; PMCID: PMC4046707
23. Zheng Y, Yu M, Padmanabhan A, Aster RH, Yuan L, Wen R, Wang D. Critical role of CD4 T cells in PF4/heparin antibody production in mice. Blood. 2015, 125:1826-1829. PMID: 25595736; PMCID: PMC4357587
24. Zheng Y, Adams T, Zhi H, Yu M, Wen R, Newman PJ, Wang D, Newman DK. Restoration of responsiveness of phospholipase Cγ2-deficient platelets by enforced expression of phospholipase Cγ1. PLoS One. 2015. DOI:10.1371/journal.pone.0119739. PMID: 25793864; PMCID: PMC4368822
25. Xin G, Schauder DM, Lainez B, Weinstein JS, Dai Z, Chen Y, Esplugues E, Wen R, Wang D, Parish IA, Zajac AJ, Craft J, Cui W. A Critical Role of IL-21-induced BATF in sustaining CD8 T-cell-mediated chronic viral control. Cell Rep. 2015, 13:1118-1124. PMID: 26527008; PMCID: PMC4859432
26. Chen Y, Zheng Y, You X^\, Yu M, Fu G, Su X, Zhou F, Zhu W, Wu Z, Zhang J, Wen R, Wang D. Kras Is Critical for B Cell Lymphopoiesis. J Immunol. 2016, 196:1678-1685. PMID: 26773157; PMCID: PMC4744498
27. Su X, Yu M, Qiu G, Zheng Y, Chen Y, Wen R, Fu G, Zhu W, Chen J, Wu N, Ma P, Chen W, Wu Z, Wang D. Evaluation of nestin or osterix promoter-driven cre/loxp system in studying the biological functions of murine osteoblastic cells. Am J Transl Res. 2016, 8:1447-1459. PMID: 27186271; PMCID: PMC4859630.
28. Fu G, Yu M, Chen Y, Zheng Y, Zhu W, Newman DK, Wang D, Wen R. Phospholipase Cγ1 is required for pre-TCR signal transduction and pre-T cell development. Eur J Immunol. 2017, 47: 74-83. PMID: 27759161, PMCID: PMC5559087.
29. Yu M, Chen Y, Zeng H, Zheng Y, Fu G, Zhu W, Broeckel U, Aggarwal P, Turner A, Neale G, Guy C, Zhu N, Chi H, Wen R, Wang D. PLCγ-dependent mTOR signalling controls IL-7-mediated early B cell development. Nat Commun. 2017, 8:1457, PMID: 29133930, PMCID: PMC5684131
30. Pamanabhan A, Jones CG, Pechauer SM, Curtis BR, Bougie DW, Irani MS, Bryant BJ, Alperin JB, Deloughery TG, Mulvey KP, Dhakal B, Wen R, Wang D, Aster RH. IVIg for Treatment of Severe Refractory Heparin-Induced Thrombocytopenia. Chest. 2017, 152: 478-485. PMID: 28427966, PMCID: PMC5812774.
31. Wang Z, Vaughan TY, Zhu W, Chen Y, Fu G, Medryzcki M, Nishio H, Bunting ST, Hankey-Giblin PA, Nusrat A, Parkos CA, Wang D, Wen R, Bunting BD. Gab2 and Gab3 Redundantly Suppress Colitis by Modulating Macrophage and CD8+ T-Cell Activation. Frontiers in Immunol. 2019, 10: 486, PMID: 30936879, PMCID: PMC6431666.
32. Wen R, Wang D. PTPRJ: A novel inherited thrombocytopenia gene. Blood. 2019, 133:1272-1274. PMID: 30898775, PMCID: PMC6428668.
33. Chen Y, Yu M, Zheng Y, Fu G, Xin G, Zhu W, Luo L, Burns R, Li QZ, Dent AL, Zhu N, Cui W, Malherbe L, Wen R, Wang D. CXCR5⁺PD-1⁺ follicular helper CD8 T cells control B cell tolerance. Nat Commun. 2019, 10: 4415, PMID: 31562329, PMCID: PMC6765049
34. Zheng Y, Zhu W, Haribhai D, Williams CB, Aster RH, Wen R, Wang D. Regulatory T Cells Control PF4/Heparin Antibody Production in Mice. J Immunol. 2019, 203: 1786-1792. PMID: 31471526, PMCID: PMC6944762.
35. Luo L, Chen Y, Chen X, Zheng Y, Zhou V, Yu M, Burns R, Zhu W, Fu G, Felix JC, Hartley C, Damnernsawad A, Zhang J, Wen R, Drobyski WR, Gao C, Wang D. Kras-deficient T cells attenuate graft-versus-host disease but retain graft-versus-leukemia activity. J Immunol. 2020, 205: 3480-3490. PMID: 33158956, PMCID: PMC7955895.
36. Wen Z, Yun G, Hebert A, Kong G, Ranheim EA, Finn R, Rajagoplan A, Li S, Zhou Y, Yu M, Damnernsawad A, Roose JP, Coon JJ, Wen R, Wang D, Zhang J. Nras Q61R/+ and Kras-/- cooperate to downregulate Rasgrp1 and promote lympho-myeloid leukemia in early T-cell precursors. Blood. 2021, 137:3259-3271, PMID: 33512434.
37. Assumpção ALFV, Fu G, Singh DK, Lu Z, Kuehnl AM, Welch R, Ong IM, Wen R, Pan X. A lineage-specific requirement for YY1 Polycomb Group protein function in early T cell development. Development. 2021, 148(7), PMID: 33766932, PMCID: PMC8077518.
38. Jobe SM, Wen R. Another front in COVID-19's perfect storm. Blood. 2021, 137:1006-1007. PMID: 33630053, PMCID: PMC7906012.