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Demin Wang, Ph.D.
Demin Wang, Ph.D. Investigator
Blood Research Institute
BloodCenter of Wisconsin Assistant Adjunct Professor
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
The development and function of myeloid and lymphoid cells are highly regulated by signals derived from a variety of cell surface receptors. Abnormal signals from the receptors often lead to hematological and immunological diseases. Our research mainly focuses on identifying and functionally characterizing signaling molecules activated by two types of receptors, the cytokine receptors and the B cell antigen receptors (BCR). 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. Our current research project studies the regulation and function of Stat5 proteins via multiple approaches, including the cutting-edge targeted gene disruption and transgenic technologies.
B cell receptor signaling  B cells are one important component of the adaptive immune system. Signals from the BCR and its surrogate predecessor pre-BCR are essential for the development, maintenance, and function of B cells. Improper signals from BCR or pre-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 project aims to fully understand the BCR signal transduction cascade by identifying novel signaling molecules of BCR and elucidating their roles in 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 cytokine and BCR receptors, to obtain new clues regarding the molecular pathogenesis of numerous hematological and immunological diseases, and to aid in the development of novel therapeutic strategies for treatment of hematologic disorders.
Selected Publications
- Quelle FW, Wang D, Nosaka T, Thierfelder WE, Stravopodis D, Weinstein Y, Ihle JN. Erythropoietin induces activation of stat5 through association with specific tyrosines on the receptor that are not required for a mitogenic response. Mol. Cell. Biol. 16:1622-1631,1996.
- Wang D, Stravopodis D, Teglund S, Kitazawa J, and Ihle JN. Naturally occurring dominant negative variants of stat5. Mol. Cell. Biol. 16:6141-6148, 1996.
- Quelle FW, Wang J, Feng J, Wang D, Cleveland JM, Ihle JN, and Zembetti GP. Cytokine rescue of p53-dependent apoptosis and cell cycle arrest is mediated by distinct JAK kinase signaling pathways. Genes Dev. 12:1099-1107, 1998.
- Teglund S, McKay C, Schuetz E, van Deursen JM, Stravopodis D, Wang D, Brown M, Bodner S, Grosveld G, and Ihle JN. Stat5 A and B proteins have essential and non-essential, or redundant, roles in cytokine response. Cell 93:841-850, 1998.
- Parganas E, Wang D, Stravopodis D, Topham DJ, Marine JC, Teglund S, Vanin EF, Bodner S, Colarnonici OR, van Deursen JM, Grosveld G, and Ihle JN. Gene disruption demonstrates a critical, non-redundant role for Jak2 in signaling through a variety of cytokine receptors. Cell 93:385-395, 1998.
- Moriggl R, Topham DJ, Teglund S, Sexl V, McKay C, Wang D, Hoffmeyer A, van Deursen J, Sangster MY, Bunting KD, Grosveld GC, and Ihle JN. Stat5 is required for IL-2-induced cell cycle progression of peripheral T cells. Immunity 10:249-259, 1999.
- Cheng M, Wang D, and Roussel MF. Expression of c-Myc in response to colony-stimulating factor-1 requires mitogen-activated protein kinase kinase-1. J. Biol. Chem. 274:6553-6558, 1999.
- Marine JC, McKay C, Wang D, Topham DJ, Parganas E, Nakajima A, Pendeville H, Yasukawa H, Sasaki A, Yoshimura A, and Ihle JN. SOCS-III is essential in the regulation of fetal liver erythropoiesis. Cell 98:617-627, 1999.
- 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.
- 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.
- Schwaller J, Parganas E, Wang D, Cain D, Aster JC, Williams IR, Lee CK, Gerthner R, Kitamura T, Frantsve J, Anastasiadou E, ML, Levy DE, Ihle JN, Gilliland GD. Stat5 is Essential for the Myelo- and Lymphoproliferative Disease Induced by TEL/JAK2 through Regulation of Oncostatin M. Molecular Cell 6:693-704, 2000.
- Wang D, Feng J, Wen R, Marine JC, Sangster MS, Parganas E, Hoffmeyer A, Jackson CW, Cleveland JM, Murray PJ, and Ihle JN. PLC-g2 is essential in the functions of B cell and Fc Receptors. Immunity 13:25-35, 2000.
- Wen R, Wang D, McKay C, Bunting KD, Marine JC, Zembetti GP, Ihle JN, and Cleveland JM. Jak-3 provides a survival signal downstream of IL-7 signaling pathway. Mol. Cell. Biol. 21:678-689, 2001.
- Wen R, Jou S, Chen Y, Hoffmeyer A and Wang D. Phospholipase Cg2 is Essential for Specific Functions of FceR and FcgR. J. Immunol. 169:6743-6752, 2002.
- Jou S, Carpino N, Takahashi Y, Piekorz R, Chao J, Carpino N, Wang D and Ihle JN. An Essential, Non-redundant Role for the Phosphoinositide 3- Kinase p110δ in Signaling by the B Cell Receptor Complex. Mol. Cell. Biol. 22:8580-8591, 2002.
- Cho MJ, Liu J, Pestina TI, Steward SA, Thomas DW, Coffman TM, Wang D, Jackson CW, and Gartner TK. The roles of aIIbb3-mediated outside-in signal transduction, thromboxane A2, and adenosine diphosphate in collagen-induced platelet aggregation. Blood 101:2646-2651, 2003.
- Chen Y, Wen R, Yang S, Schuman J, Zhang EE, Yi T, Feng GS and Wang D. Identification of Shp-2 as a Specific Stat5 Phosphatase. J. Biol. Chem. 278:16520-16527, 2003.
- Xue L, Morris SW, Orihuela C, Tuomanen E, Cui X, Wen R and Wang D. Defective development and function of follicular, marginal zone, and B1 B cells in Bcl10-deficient mice. Nat. Immunol. 4:857-865, 2003.
- Wen R, Chen Y., Xue L, Schuman J, Yang S, Morris SW and Wang D. PLCγ2 provides survival signals during B cell maturation via Bcl-2 and A1. J. Biol. Chem. 278:43654-43662, 2003.
- Zhu Y, Chen L, Huang Z, Alkan S, Bunting KD, Wen R, Wang D and Hua Huang. IL-5 Primes Th2 Cytokine-Producing Capacity in Eosinophils through a STAT5-Dependent Mechanism. J. Immunol. 173:2918-2922, 2004.
- Wen R, Chen Y, Schuman J, Yang S, Newman D and Wang D. PLCg1 plays an essential role, distinct from PLCg2, in B cell development. EMBO J. 23:4007-4017, 2004.
- Lin X and Wang D. The roles of CARMA1, Bcl10, and MALT1 in antigen receptor signaling. Invited review by Seminars in Immunology 16:429-435, 2004.
- 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.
- Regunathan J, Chen Y, Wang D and Malarkannan S. NKG2D-mediated NK cell Cytotoxicity is regulated by Inhibitory Ly49 Receptors. Blood 105:233-240, 2005.
- Zhu M, Granillo O, Wen R, Yang K, Dai X, Wang D, and Zhang W. Negative Regulation of Lymphocyte Activation by the Adaptor Protein LAX. J. Immunol. 174: 5612 – 5619, 2005.
- Mutsumoto R, Wang D, Blonska M, Li H, Kobayashi M, Pappu B, Chen Y, Wang D, Lin X. Phosphorylation of CARMA1 plays a critical role in T cell receptor-mediated NF-κB activation. Immunity 23:575-585, 2005.
- Dai X, Chen Y, Schuman J, Hua Z, Adamson JW, Wen R, Wang D. Distinct roles of PI3K and PLCg2 in B cell receptor-mediated signal transduction. Mol. Cell. Biol. 26:88-99, 2006.
- Cheeseman KL, Kashiwagi K, Michaud T, Ueyama T, Wang D, Flax LA, Shirai Y, Loegering DJ, Saito N, and Lennartz MR. Targeting of PKC-ε during FcγR-dependent phagocytosis requires the εC1B domain and phospholipase C-γ1. Mol. Biol. Cell. 17:799-813, 2006.
- Xu W, Fukuyama T, Ney PA, Wang D, Rehg J, Boyd K, van Deursen JM, and Brindle PK. Global transcriptional coactivators CREB-binding protein and p300 are highly essential collectively but not individually in peripheral B-cells. (Blood in press)
- Regunathan J, Chen Y, Kutlesa S, Dai X, Bai L, Wen R, Wang D*, and Malarkannan S*. Differential and non-redundant roles of PLCγ2 and PLCγ1 in the terminal maturation of NK cells1. (J. Immunol. In press) (*equal senior authorship)
- Chen Y, Dai X, Haas AL, Wen R, Wang D. Proteasome-dependent down-regulation of activated Stat5A in the nucleus. (Blood in press)
Grant Support - NIH R01 AI079087, PLCgs in B Cell Biology and Autoimmunity (7/1/08-6/30/13).
- NIH R01 HL73284, Stat5 Dephosphorylation by Shp-2 (4/1/03-3/31/08).
- American Cancer Society RSG CCG-106204, Role of Phospholipase Cg2 in Regulating B Cell Apoptosis (7/1/03-6/30/07).
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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