Bruce Walcheck, Ph.D.

Research Interests:

Cell adhesion: leukocyte migration

Our research group is examining various aspects of inflammation regulation.  We are interested in the mechanisms that direct 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 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.

Walcheck lab

Selected Recent Publications:

• Romee R, Foley B, Lenvik T, Wang Y, Zhang B, Ankarlo D, Luo X, Cooley S, Verneris M, Walcheck B, Miller J. 2013. NK cell CD16 surface expression and function is regulated by a disintegrin and metalloprotease-17 (ADAM17). Blood. 2013 Mar 13. [Epub ahead of print]
• Wang Y, Wu J, Newton R, Bahaie NS, Long C, Walcheck B. 2013. ADAM17 cleaves CD16b (FcγRIIIb) in human neutrophils. BBA - Mol Cell Res. 1833:680-685. 
• Long C, Hosseinkhani MR, Wang Y, Sriramarao P, and Walcheck B. 2012. ADAM17 activation in circulating neutrophils following bacterial challenge impairs their recruitment. J Leukoc Biol. 3:667-672.
• Romee R, Foley B, Levnik T, Ankarlo D, Wang Y, Zhang B, Ankarlo D, Luo X, Cooley S, Verneris MR, Walcheck B, and Miller JS. 2012. NK cell CD16 surface expression and function is regulated by a disintergrin and metalloprotease-17 (ADAM17). Blood. In press.
• Arndt PG, Strahan B, Wang Y, Long C, Horiuchi K, and Walcheck B. 2011. Leukocyte ADAM17 Regulates Acute Pulmonary Inflammation. PlosOne. 6(5): e19938.
• Wang Y., Robertson J.D., Walcheck B. 2011. Different signaling pathways induce a disintegrin and metalloprotease-17 (ADAM17) in neutrophils during apoptosis and activation. J. Biol. Chem. 286: 38980.
• Lei T, Liang X, Yang J, Yan M, Zheng L, Walcheck B, Ji Y. 2011. The C-terminal domain of the novel essential protein Gcp is critical for interaction with another essential protein YeaZ of Staphylococcus aureus. PLoS ONE. 6(5): e20163.
• Long C., Wang Y., Herrera, AH., and Walcheck, B. 2010. In vivo role of leukocyte ADAM17 in inflammation induction during E. coli infection. J. Leukoc. Biol. 87:1097.
• Wang Y., Zhang, A., Herrera, AH., Ni, Z and Walcheck, B. 2010. ADAM17 activity and other mechanisms of soluble L-selectin production during death receptor-induced leukocyte apoptosis. J. Immunol. 184:4447.
• Ni, Z. and Walcheck, B. 2009. Cutaneous lymphocyte-associated antigen (CLA) T cells up-regulate P- selectin ligand expression upon their activation.. Clinical Immunology. In press.

• Wang Y., Herrera, AH., Li, Y., and Walcheck, B. 2009. Regulation of mature ADAM17 by redox agents for L-selectin shedding. J. Immunol. 182:2449.

• St Hill, C.A., Farooqui, M., Mitcheltree, G., Gulbahce, H.E., Jessurun, J., Cao, Q., Walcheck, B. 2009. The high affinity selectin glycan ligand C2-O-sLex and mRNA
  transcripts of the core 2 beta-1,6-N-acetylglucosaminyltransferase (C2GnT1) gene are highly expressed in human colorectal adenocarcinomas.. BMC Cancer 9:79.

• Schaff, U., Mattila, P., Simon, S.I., and Walcheck, B. 2008. Neutrophil adhesion to E-selectin under shear promotes the redistribution and co-clustering of ADAM17 and its proteolytic substrate L-selectin. J. Leukoc. Biol. 83:99-105.

• Bell J., Herrera AH. Li, Y., and Walcheck B. 2007. Role of ADAM17 in the ectodomain shedding of TNF-alpha and its receptors by neutrophils and macrophages. J. Leuko. Biol. 82:173-176.

• 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.

• Li, Y., Brazzell, JL., Herrera, AH., Walcheck, B. 2006. ADAM17 deficiency by
  mature neutrophils has differential effects on L-selectin shedding. Blood 108(7):2275-9

• Ni Z, Campbell JJ, Niehans G, Walcheck B. 2006. The Monoclonal Antibody CHO-131 Identifies a Subset of CutaneousLymphocyte-Associated Antigen T Cells Enriched in P-Selectin-Binding Cells. J Immunol. 177(7):4742-8.
  

• Walcheck, B., Herrera, A.H., St. Hill, C.A., Mattila, P., Whitney, A.R., and DeLeo, F.R. 2006. ADAM17 activity during human neutrophil activation and apoptosis. 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.

• Catherine St. Hill, 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, RD., Knibbs, RN., Stoolman, LM., Alexander, SR., Mattila, PE., and McEver, RP. 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.