Demin Wang, Ph.D.
Demin Wang, Ph.D. Senior Investigator (Full Professor)
Blood Research Institute
BloodCenter of Wisconsin Adjunct Faculty
Department of Microbiology and Molecular Genetics
Medical College of Wisconsin Postdoctoral Training
St. Jude Children’s Research Hospital
Memphis, Tennessee Doctoral Training Ph.D., University of Tennessee Medical School, 1995
Selected Publications
Grant Support
Laboratory Staff
Contact Information
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 molecules that are important for HSC and B cell biology. Our research employs multiple cutting-edge approaches, including the targeted gene disruption, transgenic, and bone marrow transplantation 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 Stat5 proteins.
In addition, Gimap5 (GTPase of the Immune-Associated Protein 5) is a member of a novel family of guanosine nucleotide-binding proteins. Our recent studies discover that Gimap5 plays a critical role in the survival of HSCs and hematopoietic progenitor cells. Gimap5 enhances interaction between Mcl-1 and HSC70, thus preventing Mcl-1 degradation and maintaining mitochondrial integrity. One of our current research projects studies the molecular mechanism by which Gimap5 regulates the survival of HSCs as well as the role of Gimap5 in regulating leukemia stem cells.
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. Our current research projects also study the molecular mechanism by which signaling molecules, such as phospholipase Cγ (PLCγ), Bcl10, MALT1 and TAK1, activate NF-κB during BCR signaling 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.
Selected Publications (from total 62)
- Chen Y, Yu M, Dai X, Zogg M, Wen R, Weiler H, and Wang D. Critical role of Gimap5 in the survival of mouse hematopoietic stem and progenitor cells. J Exp Med 208:923-935; 2011.
- Wuerzberger-Davis S, Chen Y, Yang DT, Bates P, Ladell NC, Yu M, Podd A, Zeng H, Wen R, Wang D* and Miyamoto S*. Nuclear export of the NF-κB inhibitor IκBα is required for proper B cell and secondary lymphoid tissue formation. Immunity 34:188-200; 2011. *equal senior authorship
- Fu G, Chen Y, Yu M, Podd A, Schuman J, He Y, Di L, Yassai M, Haribhai D, North PE, Gorski J, Williams CB, Wang D, and Wen R. Phospholipase Cγ1 is essential for T-cell development, activation and tolerance. J Exp Med 207: 309-318; 2010.
- Schuman J, Chen Y, Podd A, Yu M, Liu H, Wen R, Chen ZJ, and Wang D. A critical role of TAK1 in B cell development and activation. Blood 113: 4566-4574; 2009.
- Chen Y, Yu M, Podd A, Wen R, Chrzanowska-Wodnicka M, White GC, and Wang D. A critical role of Rap1b in B cell trafficking and marginal zone B cell development. Blood 111: 4627-4636; 2008.
- Bai L, Chen Y, He Y, Dai X, Lin X, Wen R, and Wang D. Phospholipase Cγ2 contributes to light chain gene activation and receptor editing. Mol Cell Biol 27: 5957-5967; 2007.
- Blonska M, Pappu BP, Matsumoto R, Li H, Su B, Wang D, and Lin X. The CARMA1-Bcl10 signaling complex selectively regulates JNK2 kinase in the T cell receptor-signaling pathway. Immunity 26: 55-66; 2007.
- Wen R, Chen Y, Bai L, Fu G, Schuman J, Dai X, Zeng H, Yang C, Stephan RP, Cleveland JL, and Wang D. An essential role of phospholipase Cγ2 in early B cell development & Myc-mediated lymphomagenesis. Mol Cell Biol 26: 9364–9376; 2006.
- Chen Y, Dai X, Haas AL, Wen R, and Wang D. Proteasome-dependent down-regulation of activated Stat5A in the nucleus. Blood 108: 566-574; 2006.
- Dai X, Chen Y, Schuman J, Hua Z, Adamson JW, Wen R, and Wang D. Distinct roles of PI3K and PLCγ2 in B cell receptor-mediated signal transduction. Mol Cell Biol 26: 88-99; 2006.
- Mutsumoto R, Wang D, Blonska M, Li H, Kobayashi M, Pappu B, Chen Y, Wang D, and Lin X. Phosphorylation of CARMA1 plays a critical role in T cell receptor-mediated NF-κB activation. Immunity 23: 575-585; 2005.
- Moriggl R, Sexl V, Kenner L, Duntsch C, Stangl K, Gingras S, Hoffmeyer A, Bauer A, Piekorz R, Wang D, et al. Stat5 tetramer formation is associated with leukemogenesis. Cancer Cell 7: 87-99; 2005.
- Wen R, Chen Y, Schuman J, Yang S, Newman D, and Wang D. An important role of phospholipase Cγ1 in pre-B-cell development and allelic exclusion. EMBO J 23: 4007-4017; 2004.
- Xue L, Morris SW, Orihuela C, Tuomanen E, Cui X, Wen R, and Wang D. Defective development and function of Bcl10-deficient follicular, marginal zone and B1 B cells. Nat Immunol 4: 857-865; 2003.
- Wang D, Feng J, Wen R, Marine JC, Sangster MS, Parganas E, Hoffmeyer A, Jackson CW, Cleveland JM, Murray PJ, and Ihle JN. Phospholipase Cγ2 is essential in the functions of B cell and several Fc Receptors. Immunity 13: 25-35; 2000.
- Schwaller J, Parganas E, Wang D, Cain D, Aster JC, Williams IR, et al. Stat5 is essential for the myelo- and lympho-proliferative disease induced by TEL/JAK2 through regulation of Oncostatin M. Mol Cell 6: 693-704; 2000.
- Wang D, Moriggl R, Stravopodis D, Carpino N, Marine JC, Teglund S, Feng J, and Ihle JN. A small amphipathic α-helical region is required for transcriptional activities and proteosome-dependent turnover of the tyrosine phosphorylated Stat5. EMBO J 19: 392-399; 2000.
- Marine JC, Topham DJ, McKay C, Wang D, Parganas E, Stravopodis D, Yoshimura A, and Ihle JN. SOCS-1 deficiency causes a lymphocyte dependent perinatal lethality. Cell 98: 609-616; 1999.
- Marine JC, McKay C, Wang D, Topham DJ, Parganas E, Nakajima A, et al. SOCS-III is essential in the regulation of fetal liver erythropoiesis. Cell 98: 617-627; 1999.
- Moriggl R, Topham DJ, Teglund S, Sexl V, McKay C, Wang D, et al. Stat5 is required for IL-2-induced cell cycle progression of peripheral T cells. Immunity 10: 249-259; 1999.
- Parganas E, Wang D, Stravopodis D, Topham DJ, Marine JC, Teglund S, et al. Jak2 is essential for signaling through a variety of cytokine receptors. Cell 93: 385-395; 1998.
- Teglund S, McKay C, Schuetz E, van Deursen JM, Stravopodis D, Wang D, et al. Stat5 A and B proteins have essential and non-essential, or redundant, roles in cytokine response. Cell 93: 841-850; 1998.
Grant Support - NIH R01 AI079087 (Wang, PI) PLCγs in B Cell Biology and Autoimmunity (7/1/08-6/30/13).
- NIH P01 HL44612 (Wang, Project Leader) B cell responses in heparin-induced thrombocytopenia (12/1/10-11/30/15)
Laboratory Staff
Employment Opportunities
If opportunities are available, they will be listed on the Employment page.
Contact Information
Phone: (414) 937-3874
Fax: (414) 937-6284
E-mail: demin.wang@bcw.edu
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