B.S., Montana State University Ph.D., Montana State University Post-Doctoral, Boehringer Ingelheim Pharm.
Research Interests Our research group is examining various aspects of inflammation regulation. We are interested in mechanisms that direct white blood cells (leukocytes) to sites of inflammation and that regulate their effector activities. A key leukocyte involved in the early inflammatory response is the neutrophil, which is the most abundant leukocyte in the blood and typically at sites of acute inflammation. Various inflammatory modulators expressed by neutrophils are regulated by a process referred to as ectodomain shedding. Among other lines of research, my lab is actively involved in understanding the function and regulation of this proteolytic process in order to manipulate inflammation and bolster innate immunity or diminish damaging inflammation.
Selected Publications (For a comprehensive list of Dr. Walcheck's recent publications, refer to PubMed, a service provided by the National Library of Medicine.)
Ni, Z. and Walcheck, B. 2007. Varied levels of reactivity by different E-selectin/Fc constructs with cutaneous lymphocyte-associated antigen (CLA)+ CD4+ T cells. Immunol. Lett. 108:179
Bell, J, Herrera, AH, Li, L., and Walcheck, B. 2007. Role of ADAM17 in the ectodomain shedding of TNF-alpha and its receptors by neutrophils and macrophages. J. Leukoc. Biol. 82:173.
Schaff U, Mattila PE, Simon SI, Walcheck B. 2007. Neutrophil adhesion to E- selectin under shear promotes the redistribution and co- clustering of ADAM17 and its proteolytic substrate L-selectin. J Leukoc Biol. In press.
Duchesneau, P., Gallagher, E., Walcheck, B., and Waddell, TK. 2007. Up-regulation of leukocyte CXCR4 expression by sulfatide: An L-selectin-dependent pathway on CD4+ T cells Eur. J. Immunol. In press.
Ni, Z. and Walcheck, B. 2006. Varied levels of reactivity by different E-selectin/Fc constructs with cutaneous lymphocyte-associated antigen (CLA)+CD4+ T cells. Immunol. Lett. In press.
Ni Z, Campbell JJ, Niehans G, Walcheck B. Related Articles, Links The Monoclonal Antibody CHO-131 Identifies a Subset of Cutaneous Lymphocyte-Associated Antigen T Cells Enriched in P-Selectin-Binding Cells. J. Immunol. 2006 Oct 1;177(7):4742-8.
Li Y, Brazzell J, Herrera A, Walcheck B. Related Articles, Links ADAM17 deficiency by mature neutrophils has differential effects on L-selectin shedding. Blood. 2006 Oct 1;108(7):2275-9.
Walcheck, B., Herrera, A.H., St. Hill, C.A., Mattila, P., Whitney, A.R., and DeLeo, F.R. 2006. ADAM17 expression and function are sustained during prolonged neutrophil activity. Eur. J. Immunol. 36:968-76.
Mattila, P., Green, C.E., Schaff, U., Simon, S.I., and Walcheck, B. 2005. L-selectin clustering involves altered lipid phase partitioning and is regulated by cytoskeletal anchorage. Amer. J. Physiol. Cell Physiol. 289:323.
St. Hill, C.A., Bullard, K.M. and Walcheck, B. 2005. Expression of the high-affinity selectin glycan ligand C2-O-sLeX by colon carcinoma cells. Cancer Lett. 217:105.
Walcheck, B., Alexander, S.R., St. Hill, C.A., and Matala, E. 2003. ADAM-17-independent shedding of L-selectin. J. Leukoc. Biol. 74:389.
St. Hill, C.A., Shelia R. Alexander, and Bruce Walcheck. 2003. Indirect capture augments leukocyte accumulation on P-selectin in flowing whole blood. J. Leukoc. Biol. 73: 464.
Walcheck, B., Leppanen, A., Cummings, R.D., Knibbs, R.N., Stoolman, L.M., Alexander, S.R., Mattila, P.E., and McEver, R.P. 2002. The monoclonal antibody CHO-131 binds to a core 2 O-glycan terminated with sialyl-Lewis x, which is a functional glycan ligand for P-selectin. Blood 99:4064.
Matala, E., Alexander, S.R., Kishimoto T.K., and Walcheck B. 2001. The cytoplasmic domain of L-selectin participates in regulating L-selectin endoproteolysis. J. Immunol. 167:1617.
Alexander, S.R., Kishimoto, T.K., and Walcheck, B. 2000. Effects of selective protein kinase C inhibitors on the proteolytic downregulation of L-selectin from chemoattractant-activated neutrophils. J. Leuk. Biol. 67:415.
Kahn, J., B. Walcheck, G. Migaki, M.A. Jutila, and T.K. Kishimoto. (1998) Calmodulin regulates L-selection adhesion molecule expression and function through a protease-dependent mechansim. Cell 92:809.
Walcheck, B., J. Kahn, J.M. Fisher, B.B. Wang, R.S. Fisk, D.G. Payan, C. Feehan, R. Betageri, K. Darlak, A.F. Spatola, and T.K. Kishimoto. (1996) Neutophil rolling altered by inhibition of L-selectin shedding in vitro. Nature 380:720.
Walcheck, B., K.L. Moore, R.P. McEver, and T.K. Kishimoto. (1996) Neutrophil-neutrophil interactions under hydrodynamic shear stress involve L-selectin and PSGL-1: A mechanism that amplifies initial leukocyte accumulation on P-selectin in vitro. J. Clin. Invest. 98:1081.
Current Funding "Regulation of inflammation: sheddases and CD62L" NIH
The major goal of this project is to study the role of ADAM17 in L-selectin ectodomain shedding. Role: PI
Current Students Zhenya Ni, Ph.D. expected Spring 2008