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 HL161127, B-cell response and thrombotic complications in COVID-19
  The goal of this study is to investigate the cellular and molecular mechanism underlying SARS-CoV-2 infection induced development of prothrombotic platelet-activating antibodies. 02/01/2022-01/31/2026
  Role: Principal Investigator
• R01 HL148120, Molecular Basis of the Humoral Immune Response in Heparin-Induced Thrombocytopenia
  The goal of the study is to investigate the molecular signatures that differentiate pathogenic and non-pathogenic PF4/heparin binding antibodies in HIT patients and the prevalence of these B cells in HIT patients and healthy subjects. 06/01/2019 - 05/31/2023. (NCE) 06/01/2023 - 05/31/2024
  Role: Principal Investigator
• 2R44GM144019-02, Development of heparan sulfate-based therapeutics to treat inflammatory diseases
  The goal of the study is to develop heparan sulfate-based synthetic glycans to treat inflammatory diseases. 09/06/2023 – 07/31/2025
  Role: Co-Investigator, (PI: Katelyn Arnold)
• R01 HL130724, Wang (PI), B cell responses in heparin-induced thrombocytopenia
  The goal of this study is to investigate the cellular and molecular mechanism underlying HIT antibody production. 12/01/2021 - 11/30/2025
  Role: Co-Investigator

Click here for a complete list of publications.

Selected Publications

1. Zeng H, Di L, Fu G, Cheng Y, Gao X, Xu L, Lin X, and Wen R. Phosphorylation of Bcl10 negatively regulates T cell receptor-mediated NF-κB activation. Mol Cell Biol. 2007, 27: 5235-5245. PMID: 17502353
2. Zeng H, Chen Y, Yu M, Xue L, Gao X, Morris SW, Wang D, and Wen R. T cell ceceptor-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
3. Fu G, Chen Y, Yu M, Podd A, Di L, He Y, Williams CB, North PE, Wang D, and Wen R. Phospholipase Cγ1 is essential for T-cell development, activation and tolerance. J Exp Med. 2010, 207:309-318. PMCID: PMC2822604
4. 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
5. Fu G, Yu M, Chen Y, Zheng Y, Zhu W, Newman DK, Wang D, and 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.
6. 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.
7. Jobe SM, Wen R. Another front in COVID-19's perfect storm. Blood. 2021, 137:1006-1007. PMID: 33630053, PMCID: PMC7906012.
8. Zhu W, Zheng Y, Yu M, Wu Y, Wei J, Zhou L, Fu G, Schneider N, Jones C, Irani M, Padmanabhan A, Aster R, Wang D, Wen R. Cloned antibodies from patients with heparin-induced thrombocytopenia (HIT) provide new clues to HIT pathogenesis. Blood, 141: 1060-1069, 2023. PMID: 36493339, PMCID: PMC10023725.
9. Zheng Y, Yu M, Chen Y, Xue L, Zhu W, Fu G, Morris SW, Wen R*, Wang D*. CARD19, a Novel Regulator of the TAK1/NF-κB Pathway in Self-Reactive B Cells. J Immunol. 2023, 210: 1222-1235. PMID: 36961449, PMCID: PMC10156913, *equal senior authorship. 
10. Kanack AJ, Schaefer JK, Sridharan M, Splinter NP, Kohlhagen MC, Singh B, De Lorenzo SB, Mauch EE, Hussein MA, Shaikh M, Kumar S, Wen R, Wang D, Murray D, Padmanabhan A. Monoclonal gammopathy of thrombotic/thrombocytopenic significance. Blood, 141: 1772-1776. 2023, PMID: 36626584, PMCID: PMC10113173.