MICaB Graduate Program
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Bruce Walcheck, Ph.D.
Department of Veterinary and Biomedical Sciences
Department of Laboratory Medicine and Pathology (adjunct)
Montana State University, 1994, Ph.D.
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.
Selected Recent Publications:
- Mishra HK, Johnson TJ, Seelig DM, Walcheck B. 2016. Targeting ADAM17 in leukocytes increases neutrophil recruitment and reduces bacterial spread during polymicrobial sepsis. J Leukoc Biol. [Epub ahead of print]
- Jing Y, Ni Z, Wu J, Higgins L, Markowski TW, Kaufman DS, and Walcheck B. 2015. Identification of an ADAM17 Cleavage Region in Human CD16 (FcγRIII) and the Engineering of a Non-Cleavable Version of the Receptor in NK Cells. PLoS One. Mar 27;10(3):e0121788.
- Mishra HK, Long C, Bahaie NS, Walcheck B. 2015. Regulation of CXCR2 expression and function by a disintegrin and metalloprotease-17 (ADAM17). J Leukoc Biol. Mar;97(3):447-54.
- Becker AM, Walcheck B, Bhattacharya D. 2015. ADAM17 limits the expression of CSF1R on murine hematopoietic progenitors. Exp Hematol.43(10):44-53.
- Chen Z, Gulzar ZG, St Hill CA, Walcheck B, Brooks JD. 2014. Increased expression of GCNT1 is associated with altered O-glycosylation of PSA, PAP, and MUC1 in human prostate cancers. Prostate. 74:1059-1067.
- 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. 121:3599-3608
- Wiernik A, Foley B, Zhang B, Verneris MR, Warlick E, Ross JA, Weisdorf DJ, Walcheck B, Vallera DA, and Miller JS. 2013. Targeting natural killer cells to acute myeloid leukemia in vitro with a CD16 x 33 bispecific killer cell engager and ADAM17 inhibition. Clin Cancer Res. 19:3844.
- 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.
- 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
- Wang Y., Herrera, AH., Li, Y., and Walcheck, B. 2009.
Regulation of mature ADAM17 by redox agents for L-selectin
- 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
- 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.
- Li, Y., Brazzell, JL., Herrera, AH., Walcheck, B. 2006.
ADAM17 deficiency by
mature neutrophils has differential effects on L-selectin
- 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
- 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
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
- 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
- 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
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
- 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.