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Joel  M.  Linden
Degree(s): Ph.D.
Graduate School: University of Virginia
Primary Appointment: Professor and Vice Chairman of Research, Medicine, Cardiovascular Medicine
Research Interests:
Adenosine Signaling in Inflammation and Diabetes

Email Address: jl4v@virginia.edu
Research Description

Receptors for the purine nucleoside adenosine have been found on all mammalian tissues. We have synthesized and characterized selective agonists of A2A adenosine receptors and selective antagonists of A2B adenosine receptors. These are screened in radioligand binding assays using four subtypes of recombinant adenosine receptors and custom-made radioligands. Activation of A2A receptors exerts anti-inflammatory effects on macrophages, neutrophils and lymphocytes and receptor mRNA in induced by inflammatory stimuli. Activation of A2A adenosine receptors during reperfusion following ischemia reduces injury in heart, lung, kidney, spinal cord, liver and skin. We have shown using A2A adenosine receptor knock out mice, bone marrow chimera, Rag1 knock out mice, T cell adoptive transfer, and tissue specific receptor knock outs (cre-lox) that A2A receptor-mediated tissue proaction in conferred through granulocytes and lymphocytes. Novel selective antagonists of A2B adenosine receptors have been found to dramatically increase insulin sensitivity in diabetic animals.

Selected Publications
  • Lappas CM, Day Y J, Marshall M A, Engelhard V H and Linden J (2006) Adenosine A2A Receptor Activation Reduces Hepatic Ischemia Reperfusion Injury by Inhibiting CD1d-Dependent NKT Cell Activation. J Exp Med 203:2639-2648.
  • Linden J (2006) Cell Biology. Purinergic Chemotaxis. Science 314:1689-1690.
  • Murphree LJ, Sullivan G W, Marshall M A and Linden J (2005) Lipopolysaccharide Rapidly Modifies Adenosine Receptor Transcripts in Murine and Human Macrophages: Role of NF-KappaB in A(2A) Adenosine Receptor Induction. Biochem J 391:575-580.
  • Yang Z, Day Y J, Toufektsian M C, Xu Y, Ramos S I, Marshall M A, French B A and Linden J (2006) Myocardial Infarct-Sparing Effect of Adenosine A2A Receptor Activation Is Due to Its Action on CD4+ T Lymphocytes. Circulation 114:2056-2064.
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      Office Address: PO Box 801394, MR-5 Bldg; Room 1312, 
      Office Phone: +1 434-924-5600
      Fax Phone: +1 434-924-2828
      Web Site: http://www.healthsystem.virginia.edu/intern

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