Robert Clancy, PhD

Associate Professor, Department of Medicine

molecular mechanism of beta1 integrin signal transduction

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.
represents one publication

Associate Professor, Department of Medicine

PhD from University of Illinois

Smilowitz, Nathaniel R; Katz, Gregory; Buyon, Jill P; Clancy, Robert M; Berger, Jeffrey S

Journal of thrombosis & thrombolysis. 2018 Jan; 45(1):13-17

Ainsworth, Hannah C; Marion, Miranda C; Bertero, Tiziana; Brucato, Antonio; Cimaz, Rolando; Costedoat-Chalumeau, Nathalie; Fredi, Micaela; Gaffney, Patrick; Kelly, Jennifer; Levesque, Kateri; Maltret, Alice; Morel, Nathalie; Ramoni, Veronique; Ruffatti, Amelia; Langefeld, Carl D; Buyon, Jill P; Clancy, Robert M

Arthritis & rheumatology. 2017 Oct 17; 69(11):2170-2174

Autoimmune reactivity to malondialdehyde adducts in SLE is associated with high disease activity [Meeting Abstract]

Hardt, Uta; Larsson, Anders; Gunnarsson, Iva; Clancy, Robert M; Silverman, Gregg J; Svenungsson, Elisabet; Gronwall, Caroline

Scandinavian journal of immunology. 2017 OCT; 86(4):330-330

Apolipoprotein L1 Risk Variants Associate with Hypertension and Nephritis Progression Despite Lower dsDNA Titers in Ghanaian Systemic Lupus Erythematous Patients [Meeting Abstract]

Blazer, Ashira; Dey, Ida Dzifa; Rasmussen, Sara; Clancy, Robert M; Buyon, Jill P

Arthritis & rheumatology. 2017 OCT; 69:?-?

Lupus Nephritis in Isolation or Accompanied By Extra-Renal Manifestations: Early Lessons from the Accelerating Medicines Partnership [Meeting Abstract]

James, Judith A; Petri, Michelle; Putterman, Chaim; Diamond, Betty; Wofsy, David; Lee, Chun Hao; Fine, Derek; Broder, Anna R; Clancy, Robert M; Izmirly, Peter M; Belmont, Michael; Bornkamp, Nicole; Davidson, Anne; Tosta, Patti; Kalunian, Kenneth C; Park, Meyeon; Dall'Era, Maria; Furie, Richard; Massarotti, Elena; Hernandez, German T; Payan-Schober, Fernanda; Connery, Sean M; Kamen, Diane L; Lee, Iris; Pendergraft, William, III; Anolik, Jennifer H; Shah, Ummara; Raychaudhuri, Soumya; Lee, Yvonne C; Guthridge, Joel M; Holers, VMichael; Utz, Paul J; Pichavant, Mina; Gupta, Rohit; Maecker, Holden T; Weisman, Michael; Buyon, Jill P

Arthritis & rheumatology. 2017 OCT; 69:?-?

Cardiac Endothelial Cell Transcriptome Analyses Support a Pathological Role of Metabolic and Inflammasome Genes in Anti-SSA/Ro-Associated Congenital Heart Block [Meeting Abstract]

Rasmussen, Sara; Clancy, Robert M; Buyon, Jill P

Arthritis & rheumatology. 2017 OCT; 69:?-?

Pathological Roles By Siglec and Type I Interferons for the Development of Autoimmune Congenital Heart Block [Meeting Abstract]

Clancy, Robert M; Halushka, Marc; Buyon, Jill P

Arthritis & rheumatology. 2017 OCT; 69:?-?

Interferon-Induced APOL1 over-Expression Causes Autophagic Dysfunction and Mitochondrial Stress in Risk Variant-Carrying Endothelial Cells [Meeting Abstract]

Blazer, Ashira; Rasmussen, Sara; Markham, Androo; Mehta-Lee, Shilpi; Buyon, Jill P; Clancy, Robert M

Arthritis & rheumatology. 2017 OCT; 69:?-?