Robert Clancy, PhD

Associate Professor, Department of Medicine

Keywords
molecular mechanism of beta1 integrin signal transduction
Summary

The interaction between the extracellular matrix and cells affects a wide spectrum of cellular processes including migration, growth, death, capacity to degrade matrix, capacity to synthesize matrix, differentiation, and cell attachment. In human neutrophils, we study signalling by beta1 integrin receptors which contribute to cell attachment and migration. Additionally, we study the effect of nitric oxide, an inflammatory mediator, on the signalling pathways. Neutrophils help destroy foreign invaders at tissue sites but first must reversibly undergo cell attachment through the endothelium and matrix. We hypothesize that nitric oxide modulates matrix-cell interaction by the reversible inhibition of neutrophil attachment to fibronectin (ligand for beta1 integrin)-coated surfaces. We recently showed that nitric oxide inhibits adherence associated with a stimulation of actin-ADP ribosylation. In bovine chondrocytes, we study signalling by beta1 integrin receptors which contribute to the capacity to degrade matrix and differentiation. We hypothesize that nitric oxide, a mediator of arthritis, inhibits chondrocyte adherence and cell capacity to contribute to matrix synthesis and breakdown. Recently, we studied signalling by beta1 integrins in chondrocytes by measuring protein accumulation to contact sites in chondrocytes exposed to fibronectin-coated and albumin-coated beads. Chondrocytes exposed to albumin-coated beads failed to generate a response, but cytoskeletal and signalling molecules accumulated to fibronectin-coated and albumin-coated beads which include polymerized actin, focal adhesion kinase, and the accumulation of tyrosine phosphorylated proteins (see Figure). Prior treatment of chondrocytes with catabolic cytokines (which stimulate nitric oxide synthesis) prevent the response. Collectively, our results suggest that nitric oxide induced a persistently altered chondrocyte phenotype (chondrocytes incapable of signalling via beta 1 integrins) which might be reversed or prevented by using nitric oxide antagonists. A persistently altered state in chondrocytes would greatly change the ability of such chondrocytes to mature and perhaps result in the changes seen in arthritis.

These focus areas and their associated publications are derived from medical subject headings from PubMed.
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Associate Professor, Department of Medicine

PhD from University of Illinois

Blazer, Ashira D; Clancy, Robert M

Current rheumatology reports. 2017 Mar; 19(3):13-13

Nhek, Sokha; Clancy, Robert; Lee, Kristen A; Allen, Nicole M; Barrett, Tessa J; Marcantoni, Emanuela; Nwaukoni, Janet; Rasmussen, Sara; Rubin, Maya; Newman, Jonathan D; Buyon, Jill P; Berger, Jeffrey S

Arteriosclerosis, thrombosis, & vascular biology. 2017 Feb 2; 37(4):707-716

Reed, Joanne H; Gorny, Miroslaw K; Li, Liuzhe; Cardozo, Timothy; Buyon, Jill P; Clancy, Robert M

Journal of autoimmunity. 2017 Jan 22; 79:99-104

Development of autoimmune diseases and genetic predisposition in children with neonatal lupus and their unaffected siblings [Meeting Abstract]

Romero, A G; Izmirly, P M; Ainsworth, H C; Marion, M; Langefeld, C; Clancy, R; Buyon, J P; Saxena, A

Arthritis & rheumatology. 2016 Oct; Conference:(American):4169-4170

Apolipoprotein l1 risk variants associate with prevalent cardiovascular disease in african american systemic lupus erythematous patients [Meeting Abstract]

Blazer, A; Clancy, R M; Belmont, H M; Izmirly, P M; Markham, A; Buyon, J P

Arthritis & rheumatology. 2016 Oct; Conference:(American):4151-4152

Dermal fibroblasts from patients with lupus nephritis express an anti-fibrotic transcriptome [Meeting Abstract]

Clancy, R M; Der, E; Akat, K; Broder, A R; Belmont, H M; Izmirly, P M; Goilav, B; Tuschl, T; Putterman, C; Buyon, J P

Arthritis & rheumatology. 2016 Oct; Conference:(American):2665-2667

Cyclic amp, ERK5, and transdifferentiation of cardiac fibroblasts in the pathogenesis of autoimmune congenital heart block [Meeting Abstract]

Markham, A; Rasmussen, S; Blumenberg, M; Clancy, R M; Buyon, J P

Arthritis & rheumatology. 2016 Oct; Conference:(American):3179-3181

Platelet FcgammaRIIA polymorphism H131R associates with subclinical atherosclerosis and increased platelet activity in SLE [Meeting Abstract]

Rasmussen, S; Reynolds, H; Buyon, J P; Nhek, S; Newman, J; Berger, J; Clancy, R M

Arthritis & rheumatology. 2016 Oct; Conference:(American):2663-2664