Demin Wang, PhD
Senior Investigator, Versiti Blood Research Institute; Professor
Locations
- Microbiology & Immunology
Contact Information
General Interests
Education
Research Interests
During hematopoiesis, hematopoietic stem cells (HSCs) give rise to all blood cells, including erythroid, myeloid and lymphoid lineages. The self-renewal and hematopoietic differentiation of HSCs are strictly controlled by both extrinsic and intrinsic signals. B cells, a subtype of lymphoid cells, are critical to the immune defense, and their development and function are also highly regulated by signals derived from a variety of cell surface receptors. Abnormal signals from the receptors often lead to hematological and immunological diseases, including hematopoietic malignancies, and immunodeficiency and autoimmune diseases. Our research focuses on identifying and functionally characterizing signaling pathways that control B cell development from hematopoietic stem cells (HSCs) and B cell function. Our research employs multiple cutting-edge approaches, including targeted gene disruption, transgenic, bone marrow transplantation and high-throughput DNA/RNA sequencing technologies.
Cytokine receptor signaling
Upon binding of cytokines, cytokine receptors initiate signals to regulate a variety of cellular responses, including cell growth, survival, differentiation, and function during hematopoiesis. Engagement of cytokine receptors induces the activation of the JAK family of cytoplasmic protein tyrosine kinases. In turn, Jaks activate components of diverse signal transduction pathways, including members of the Signal Transducers and Activators of Transcription (Stat). The importance of the JAKs and Stats in signaling has been emphasized by gene disruption studies. Dysregulation of JAK/Stat pathway has been implicated in the pathogenesis of numerous hematological diseases. One of our current research projects studies the regulation and function of Stat proteins.
B cell receptor signaling
B cells are one important component of the adaptive immune system. Signals from the B cell antigen receptor (BCR) and its surrogate predecessor pre-BCR are essential for the development, maintenance and function of B cells. Improper signals from pre-BCR/BCR often result in immunodeficiency, autoimmunity, and B-cell leukemia. During last decade, a wide variety of signaling molecules involved in BCR function have been discovered. Our current research projects aim to fully understand the pre-BCR/BCR signal transduction cascade by identifying novel signaling molecules of the pre-BCR/BCR and investigate the roles of these signaling molecules in pre-BCR/BCR-mediated B cell development and function in vivo.
The long term goals of our research program aim to establish a thorough understanding of the normal signaling pathways of the cytokine and pre-BCR/BCR receptors, to obtain new clues regarding the molecular pathogenesis of numerous hematological and immunological diseases, including acute or chronic hematopoietic malignancies, and immunodeficiency (such as agammaglobulinemia and common variable immunodeficiency) and autoimmune (such as systemic lupus erythematosus, rheumatoid arthritis, type I diabetes, multiple sclerosis, hemolytic anemia, and heparin-induced thrombocytopenia) diseases, and to aid in the development of novel therapeutic strategies for treatment of these hematological and immunological disorders.
Publications
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(Zhang Y, Lin D, Zheng Y, Chen Y, Yu M, Cui D, Huang M, Su X, Sun Y, Chen Y, Qian Z, Carlson KS, Wen R, Wang D.) Leukemia. 2023 Nov;37(11):2261-2275 PMID: 37670087 PMCID: PMC10844005 SCOPUS ID: 2-s2.0-85169811460 09/06/2023
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(Zheng Y, Yu M, Chen Y, Xue L, Zhu W, Fu G, Morris SW, Wen R, Wang D.) J Immunol. 2023 May 01;210(9):1222-1235 PMID: 36961449 PMCID: PMC10156913 SCOPUS ID: 2-s2.0-85152627989 03/25/2023
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(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.) Blood. 2023 Apr 06;141(14):1772-1776 PMID: 36626584 PMCID: PMC10113173 SCOPUS ID: 2-s2.0-85149641390 01/11/2023
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(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.) Blood. 2023 Mar 02;141(9):1060-1069 PMID: 36493339 PMCID: PMC10023725 SCOPUS ID: 2-s2.0-85147273278 12/10/2022
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(Zhang Z, Dai W, Zhu W, Rodriguez M, Lund H, Xia Y, Chen Y, Rau M, Schneider EA, Graham MB, Jobe S, Wang D, Cui W, Wen R, Whiteheart SW, Wood JP, Silverstein R, Berger JS, Kreuziger LB, Barrett TJ, Zheng Z.) Research and Practice in Thrombosis and Haemostasis. August 2023;7(6) SCOPUS ID: 2-s2.0-85169507694 08/01/2023
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(Wen R, Wang D.) Blood. 2022 Sep 08;140(10):1058-1059 PMID: 36074533 PMCID: PMC9461468 SCOPUS ID: 2-s2.0-85137324355 09/09/2022
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(Kanack AJ, Bayas A, George G, Abou-Ismail MY, Singh B, Kohlhagen MC, Splinter NP, Christ M, Naumann M, Moser KA, Smock KJ, Grazioli A, Wen R, Wang D, Murray DL, Padmanabhan A.) Blood. 2022 Jul 07;140(1):73-77 PMID: 35560046 PMCID: PMC9262283 SCOPUS ID: 2-s2.0-85133918941 05/14/2022
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(Bluemn T, Schmitz J, Zheng Y, Burns R, Zheng S, DeJong J, Christiansen L, Arnold O, Izaguirre-Carbonell J, Wang D, Deshpande AJ, Zhu N.) Leukemia. 2022 Apr;36(4):946-955 PMID: 35022500 PMCID: PMC10095935 SCOPUS ID: 2-s2.0-85122690302 01/14/2022
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(Wang F, Cui D, Zhang Q, Shao Y, Zheng B, Chen L, Luo Y, Yuan L, Wang D.) Immunology. 2022 Jan;165(1):88-98 PMID: 34435359 SCOPUS ID: 2-s2.0-85114376236 08/27/2021
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(Lee-Sundlov MM, Burns RT, Kim TO, Grozovsky R, Giannini S, Rivadeneyra L, Zheng Y, Glabere SH, Kahr WHA, Abdi R, Despotovic JM, Wang D, Hoffmeister KM.) Blood. 2021 Dec 09;138(23):2408-2424 PMID: 34324649 PMCID: PMC8662070 SCOPUS ID: 2-s2.0-85120725620 07/30/2021
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(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.) Blood. 2021 Jun 10;137(23):3259-3271 PMID: 33512434 PMCID: PMC8351901 SCOPUS ID: 2-s2.0-85107817855 01/30/2021
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(Chen Y, Wang D.) Blood. 9 December 2021;138(23):2303-2305 SCOPUS ID: 2-s2.0-85120728825 12/09/2021