Bruce Neil Cronstein

Biosketch / Results /

Bruce Cronstein

Dr. Paul R. Esserman Professor of Medicine, Department of Medicine;Professor, Department of Biochemistry and Molecular Pharmacology;Professor, Department of Pathology
Medicine

Contact Info

Address
227 East 30th Street
New York, NY 10016

212/263-6404


Education

1977-1978 — NYU Medical Center (Pathology), Residency Training
1977-1978 — Bellevue Hospital Center (Pathology), Residency Training
1977-1978 — Department of Veterans Affairs-New York Campus (Pathology), Residency Training
1978-1980 — Lenox Hill Hospital (Medicine (Internal)), Residency Training
1980-1983 — NYU Medical Center, Clinical Fellowships
1980-1983 — Department of Veterans Affairs-New York Campus, Clinical Fellowships
1980-1983 — Bellevue Hospital Center, Clinical Fellowships

Research Summary

Adenosine is released from most cells and tissues as a result of ATP catabolism in response to such stresses as hypoxia and inflammatory injury. Adenosine regulates numerous physiologic functions via interaction with one or more of at least four known receptors (A1, A2A, A2B, A3), all of which are members of the family of G protein-coupled receptors. At least one adenosine receptor type, and generally more than one type, is expressed on nearly every cell type and tissue examined. We first demonstrated the presence and function of both A1 and A2 adenosine receptors on human polymorphonuclear leukocytes and their critical role in regulating inflammation. In more recent studies we have shown that adenosine, acting at its receptors, mediates the antiinflammatory effects of methotrexate, the most commonly used drug in the treatment of Rheumatoid Arthritis. My laboratory continues to explore the mechanism by which adenosine receptors modulate cellular functions. Inflammation is a critical first step in dealing with tissue injury and for preventing superinfection at wounded sites. Because inflammation is the first step in wound healing we asked whether adenosine receptor agonists might promote wound healing. We have demonstrated that topical application of adenosine A2A receptor agonists stimulates more rapid wound healing, a phenomenon we have helped take into the clinic where an adenosine A2A receptor agonist is undergoing clinical trials for the promotion of healing of diabetic foot ulcers. We have explored the mechanism by which adenosine A2A receptor agonists promote wound healing and found that occupancy of A2A receptors by adenosine or its more selective and potent agonists promotes new blood vessel formation and new matrix formation by fibroblasts. Thus, adenosine A2A receptor agonists may be useful in stimulating wound healing. Because adenosine A2A receptor agonists stimulate more rapid and exuberant wound healing we determined whether adenosine A2A receptors were involved in scar formation although the scarring we examined was in the liver. We found that adenosine A2A receptors play a critical role in animal models of liver fibrosis and that agents that block these receptors could be used to block the development of liver cirrhosis/fibrosis, an important public health problem. Current research in the laboratory is focused on understanding the molecular mechanisms by which adenosine concentrations are increased in the extracellular space and how adenosine and its receptors regulate inflammation, wound healing and fibrosis.

Research Interests

Adenosine-mediated regulation of inflammation, wound healing, fibrosis and bone resorption and the pharmacology of adenosine receptors

Brief Report: Methotrexate prevents wear particle-induced inflammatory osteolysis in mice via activation of adenosine A2A receptor
Mediero, A; Perez-Aso, M; Wilder, T; Cronstein, BN
2015-04-10; 2326-5191,Arthritis & rheumatology - id: 1523512, year: 2015

Netrin-1 is a critical autocrine/paracrine factor for osteoclast differentiation
Mediero, Aranzazu; Ramkhelawon, Bhama; Perez-Aso, Miguel; Moore, Kathryn J; Cronstein, Bruce N
2015-04-27; 1523-4681,Journal of bone & mineral research - id: 1543872, year: 2015 Journal Article

Direct or indirect stimulation of adenosine A2A receptors enhances bone regeneration as well as bone morphogenetic protein-2
Mediero, Aranzazu; Wilder, Tuere; Perez-Aso, Miguel; Cronstein, Bruce N
2015-04-06; 1530-6860,FASEB journal - id: 1520492, year: 2015 Journal Article

Adenosine A(2A) receptor as a potential new therapeutic target for the prevention/treatment of osteoarthritis
Corciulo, Carmen; Mediero, Aranzazu; Wilder, Tuere; Cronstein, Bruce
2015-03-06; 1573-9546,Purinergic signalling - id: 1477352, year: 2014

Adenosine receptors and tissue fibrosis
Cronstein, Bruce N; Perez Aso, Miguel; Feig, Jessica
2015-03-06; 1573-9546,Purinergic signalling - id: 1477342, year: 2014