Credentials
Positions
- Professor, Department of Medicine at NYU Grossman School of Medicine
- Professor, Department of Biochemistry and Molecular Pharmacology at NYU Grossman School of Medicine
- Chief of Rheumatology, VA NY Harbor Health Care System
- Director, Rheumatology Fellowship Program
- Director, Clinical and Translational Science Institute Education and Careers Unit
Board Certifications
- American Board of Internal Medicine (Rheumatology), 1992
Education and Training
- Fellowship, New York University School of Medicine, Rheumatology, 1993
- Residency, Jacobi Medical Center, Internal Medicine, 1990
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Interests
signal transduction and the regulation of cells involved in inflammation and rheumatoid arthritis
Research Summary
In rheumatoid arthritis (RA) the tissues of the involved joints assume inflammatory, autoimmune and pseudoneoplastic features. The cells contributing to these phenotypes include neutrophils, which accumulate in the RA joint space, and synovial fibroblasts (SFs), which proliferate in great numbers in the RA synovium (pannus) and secrete matrix metalloproteinases (MMPs) that participate in the destruction of cartilage.
The mitogen-activated protein kinases (MAPKs) include the Erks, Jnks and p38. Our laboratory is interested in the role of MAPKs on neutrophils and SF regulation. We are especially interested in the role of Erks. We have observed that, in neutrophils, Erk is rapidly activated in response to chemoattractants and regulates neutrophil adhesion, a critical early step in the acute inflammation. In SFs we have shown that Erk regulates proliferation, but also the release of some (MMP-1,3,9) but not other (MMP-13) metalloproteinases. Interestingly, high-dose salicylates (doses achievable in patients but in excess of those needed to inhibit cyclooxygenase) inhibit Erk in both neutrophils and SFs, and concordantly inhibit neutrophil adhesion and SF MMP release. Non-salicylate nonsteroidals also inhibit cyclooxygenase but do not reproduce these effects. Indeed, COX inhibition actually leads to enhancement of MMP release from synovial fibroblasts.
Our present aims are threefold: 1) to understand the mechanisms through which Erk positively regulates neutrophil adhesion; 2) to understand the cross talk between prostaglandin production and Erk activation in SF responses; 3) to understand the mechanisms through which salicylates inhibit Erk, as a clue into how Erk, and other signaling pathways, may be pharmacologically targeted. A better understanding of these phenomena may lead to new approaches, and new agents, for the treatment of RA.}
Research Interests Timeline
Clinical Trials and Research Studies
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Colchicine for the Treatment of Osteoarthritis of the Knee (CLOAK)
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An observational study assessing the prevalence of lumbosacral spinal urate deposition in patients with tophaceous and non-tophaceous gout compared with non-gout controls using Dual-Energy CT (DECT)
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SAMPLE (Specimen and Matched Phenotype Linked Evaluation)
Publications
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Samuels, Jonathan; Pillinger, Michael H; Jevsevar, David; Felson, David; Simon, Lee S
Osteoarthritis & cartilage. 2021 Jan ; 29(1):8-16
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Ho, Gary H; Pillinger, Michael H; Toprover, Michael
Current opinion in rheumatology. 2020 Dec 15; Publish Ahead of Print: