Provide the following information for the key personnel and other significant contributors.
Follow this format for each person. DO NOT EXCEED FOUR PAGES.
NAME
Joel M. Linden / POSITION TITLE
Member
eRA COMMONS USER NAME
Joel_Linden
EDUCATION/TRAINING (Begin with baccalaureate or other initial professional education, such as nursing, and include postdoctoral training.)
INSTITUTION AND LOCATION / DEGREE
(if applicable) / YEAR(s) / FIELD OF STUDY
Brown University, Providence, RI / B.S. / 1974 / Applied Mathematics/Biology
University of Virginia, Charlottesville, VA / Ph.D. / 1978 / Pharmacology
A. POSITIONS AND HONORS
Positions and Employment
Year Department Position Institution
1978-79 Pharmacology Research Asst Professor University of Virginia
1982-86 Cardiovascular Research Assistant Member Oklahoma Med.Res. Fndn.
1986/89 Medicine/Physiology Asst/Assoc Professor U. Virginia
1994-2009 Medicine/Pharmacology Professor/Adjunct Professor
1999- 2009 Founder, Science Advisor Adenosine Therapeutics
2006-2009 Medicine Vice Chairman of Research U. Virginia
2009 – present Inflammation Biology Member La Jolla Inst. Allergy Immunol
Honors and Awards
Invited Speaker 38 international Symposia; Recipient Merrick Research Award, Oklahoma Medical Research Foundation 84; American Heart Association: Established Investigator, 85-90; Chairman Peer Review Subcommittee, Virginia Heart Association, 94; Chairman Research Committee, 97; Chairman Mid Atlantic Research Committee, 01.; NIH Study Sections: Pharmacology; 93; 99; 00-03; NIAAA , 93; parent SCOR- Heart Diseases, 94; Reverse Site Visit Chairman, 94; Cardiovascular A, 95, 97, 99; NIDDK Board of Scientific Counselors, 96; Clinical Sciences Special Emphasis Panels, Chairman, 96 & 97; MIM, 04, 05; NHLBI Special Review Committees, 96, 97, 98, 99, 00, 05, 07 Chairman; NYU GCRC, 03; Cardiovascular Sciences SBIR, 04; Goodman & Gilman Award selection committee, 98, Chairman, 00. UVa Edlich-Henderson Inventor of the Year Award, 02; Geisinger Institute James R Neely Memorial Lectureship, 02. Distinguished Lecturer, Creighton University, 2009; Editorial Boards, Molecular Pharmacology, 1994-2009; Journal of Vascular Research, 1995-2006; Purinergic Signaling, 2004-present.
B. Publications (selected from 261 articles, 20 book chapters and 1 book editor):
Fredholm BB, IJzerman AP, Jacobson KA, Klotz KN and Linden J. International Union of Pharmacology. XXV. Nomenclature and classification of adenosine receptors. Pharmacol Rev 53: 527-552, 2001.
Gao Z, Li BS, Day YJ and Linden J. A3 adenosine receptor activation triggers phosphorylation of protein kinase B and protects rat basophilic leukemia 2H3 mast cells from apoptosis. Mol Pharmacol 59: 76-82, 2001.
Hettinger BD, Lee A, Linden J and Rosin DL. Ultrastructural localization of adenosine A2A receptors suggests multiple cellular sites for modulation of GABAergic neurons in rat striatum. J Comp Neurol 431: 331-346, 2001.
Linden J. Molecular approach to adenosine receptors: receptor-mediated mechanisms of tissue protection. Annu Rev Pharmacol Toxicol 41: 775-787, 2001.
Rieger JM, Brown ML, Sullivan GW, Linden J and Macdonald TL. Design, synthesis, and evaluation of novel A2A adenosine receptor agonists. J Med Chem 44: 531-539, 2001.
Kim SA, Marshall MA, Melman N, Kim HS, Muller CE, Linden J and Jacobson KA. Structure-activity relationships at human and rat A2B adenosine receptors of xanthine derivatives substituted at the 1-, 3-, 7-, and 8-positions. J Med Chem 45: 2131-2138, 2002.
Murphree LJ, Marshall MA, Rieger JM, Macdonald TL and Linden J. Human A(2A) adenosine receptors: high-affinity agonist binding to receptor-G protein complexes containing Gbeta(4). Mol Pharmacol 61: 455-462, 2002.
Lutjens H, Zickgraf A, Figler H, Linden J, Olsson RA and Scammells PJ. 2-Amino-3-benzoylthiophene Allosteric Enhancers of A(1) Adenosine Agonist Binding: New 3, 4-, and 5-Modifications. J Med Chem 46: 1870-1877, 2003.
Day, Y-J., Huang, L., McDuffie, M. J., Rosin, D. L., Ye, H., Chen, J. F., Schwarzschild, M. A., Fink, J. S., Linden, J., and Okusa, M. D. Renal protection from ischemia mediated by A2A adenosine receptors on bone marrow-derived cells. J.Clin.Invest. 112: 883-891, 2003.
Figler H, Olsson RA and Linden J. Allosteric enhancers of A(1) adenosine receptors increase receptor-G protein coupling and counteract guanine nucleotide effects on agonist binding. Molecular Pharmacology 64: 1557-1564, 2003.
Bucheimer RE, Linden J. Purinergic regulation of epithelial transport. Journal of Physiology-London 2004 555(2):311-21.
Lappas CM, Rieger JM and Linden J. A2A Adenosine Receptor Induction Inhibits IFN- Production in Murine CD4+ T Cells. J Immunol 174: 1073-1080, 2005.
Linden J: Adenosine in tissue protection and tissue regeneration. Mol Pharmacol 2005, 67:1385-1387.
Yang Z, Day YJ, Toufektsian MC, Ramos SI, Marshall M, Wang XQ, French BA and Linden J. Infarct-sparing effect of A2A-adenosine receptor activation is due primarily to its action on lymphocytes. Circulation 111: 2190-2197, 2005.
Day YJ, Li Y, Rieger JM, Ramos SI, Okusa MD and Linden J. A2A adenosine receptors on bone marrow-derived cells protect liver from ischemia-reperfusion injury. J Immunol 174: 5040-5046, 2005.
Murphree LJ, Sullivan GW, Marshall MA and Linden J. Lipopolysaccharide rapidly modifies adenosine receptor transcripts in murine and human macrophages: role of NF-kappa B in A(2A) adenosine receptor induction. Biochemical Journal 391: 575-580, 2005.
Chordia MD, Zigler M, Murphree LJ, Figler H, Macdonald TL, Olsson RA and Linden J. 6-aryl-8H-indeno[1,2-d]thiazol-2-ylamines: A1 adenosine receptor agonist allosteric enhancers having improved potency. J Med Chem 48: 5131-5139, 2005.
Day YJ, Li Y, Rieger JM, Ramos SI, Okusa MD and Linden J. A2A adenosine receptors on bone marrow-derived cells protect liver from ischemia-reperfusion injury. J Immunol 174: 5040-5046, 2005.
Linden J. Adenosine in tissue protection and tissue regeneration. Mol Pharmacol 67: 1385-1387, 2005.
Murphree LJ, Sullivan GW, Marshall MA and Linden J. 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, 2005.
Yang Z, Day YJ, Toufektsian MC, Ramos SI, Marshall M, Wang XQ, French BA and Linden J. Infarct-sparing effect of A2A-adenosine receptor activation is due primarily to its action on lymphocytes. Circulation 111: 2190-2197, 2005.
Lappas CM, Day YJ, Marshall MA, Engelhard VH and Linden J. Adenosine A2A receptor activation reduces hepatic ischemia reperfusion injury by inhibiting CD1d-dependent NKT cell activation. J Exp Med 203: 2639-2648, 2006.
Li Y, Oskouian RJ, Day YJ, Rieger JM, Liu L, Kern JA and Linden J. Mouse spinal cord compression injury is reduced by either activation of the adenosine A2A receptor on bone marrow-derived cells or deletion of the A2A receptor on non-bone marrow-derived cells. Neuroscience 141: 2029-2039, 2006.
Linden J. Cell biology. Purinergic chemotaxis. Science 314: 1689-1690, 2006.
Linden J. New insights into the regulation of inflammation by adenosine. J Clin Invest 116: 1835-1837, 2006.
McIntire WE, MacCleery G, Murphree LJ, Kerchner KR, Linden J and Garrison JC. Influence of differential stability of G protein betagamma dimers containing the gamma11 subunit on functional activity at the M1 muscarinic receptor, A1 adenosine receptor, and phospholipase C-beta. Biochemistry 45: 11616-11631, 2006.
Naganuma M, Wiznerowicz EB, Lappas CM, Linden J, Worthington MT and Ernst PB. Cutting edge: Critical role for A2A adenosine receptors in the T cell-mediated regulation of colitis. J Immunol 177: 2765-2769, 2006.
Yang Z, Day YJ, Toufektsian MC, Xu Y, Ramos SI, Marshall MA, French BA and Linden J. Myocardial infarct-sparing effect of adenosine A2A receptor activation is due to its action on CD4+ T lymphocytes. Circulation 114: 2056-2064, 2006.
Rivo J, Zeira E, Galun E, Einav S, Linden J and Matot I. Atenuation of reperfusion lung injury and apoptosis by A2A adenosine receptor activation is associated with modulation of bcl-2 and bax expression and activation of extracellular signal-regulated kinases. Shock 27: 266-273, 2007.
Sevigny CP, Li L, Awad AS, Huang L, McDuffie M, Linden J, Lobo PI and Okusa MD. Activation of adenosine 2A receptors attenuates allograft rejection and alloantigen recognition. J Immunol 178: 4240-4249, 2007.
Deaglio S, Dwyer KM, Gao W, Friedman D, Usheva A, Erat A, Chen JF, Enjyoji K, Linden J, Oukka M, Kuchroo VK, Strom TB and Robson SC. Adenosine generation catalyzed by CD39 and CD73 expressed on regulatory T cells mediates immune suppression. J Exp Med 2007.
Reutershan J, Cagnina RE, Chang D, Linden J and Ley K. Therapeutic anti-inflammatory effects of myeloid cell adenosine receptor A2a stimulation in lipopolysaccharide-induced lung injury. J Immunol 179: 1254-1263, 2007.
Clark AN, Youkey R, Liu X, Jia L, Blatt R, Day YJ, Sullivan GW, Linden J and Tucker AL. A1 Adenosine Receptor Activation Promotes Angiogenesis and Release of VEGF From Monocytes. Circ Res 2007.
Zarek PE, Huang CT, Lutz ER, Kowalski J, Horton MR, Linden J, Drake CG and Powell JD. A2A receptor signaling promotes peripheral tolerance by inducing T-cell anergy and the generation of adaptive regulatory T cells. Blood 111: 251-259, 2008. Published prior to April 7, 2008.
Awad AS, Rouse M, Liu L, Vergis AL, Rosin DL, Linden J, Sedor JR and Okusa MD. Activation of adenosine 2A receptors preserves structure and function of podocytes. J Am Soc Nephrol 19: 59-68, 2008. Published prior to April 7, 2008.
Yu L, Shen HY, Coelho JE, Araujo IM, Huang QY, Day YJ, Rebola N, Canas PM, Rapp EK, Ferrara J, Taylor D, Muller CE, Linden J, Cunha RA and Chen JF. Adenosine A2A receptor antagonists exert motor and neuroprotective effects by distinct cellular mechanisms. Ann Neurol 63: 338-346, 2008. Published prior to April 7, 2008.
Rork TH, Wallace KL, Kennedy DP, Marshall MA, Lankford AR and Linden J. Adenosine A2A receptor activation reduces infarct size in the isolated, perfused mouse heart by inhibiting resident cardiac mast cell degranulation. Am J Physiol Heart Circ Physiol 2008. PMCID 2614589
Hasko G, Linden J, Cronstein B and Pacher P. Adenosine receptors: therapeutic aspects for inflammatory and immune diseases. Nat Rev Drug Discov 7: 759-770, 2008. PMCID 2568887
Ferguson GN, Valant C, Horne J, Figler H, Flynn BL, Linden J, Chalmers DK, Sexton PM, Christopoulos A and Scammells PJ. 2-aminothienopyridazines as novel adenosine A1 receptor allosteric modulators and antagonists. J Med Chem 51: 6165-6172, 2008.
Moore CC, Martin EN, Lee GH, Obrig T, Linden J and Scheld WM. An A2A adenosine receptor agonist, ATL313, reduces inflammation and improves survival in murine sepsis models. BMC Infect Dis 8: 141, 2008. PMC2588444
Yang Z, Linden J, Berr SS, Kron IL, Beller GA and French BA. Timing of adenosine 2A receptor stimulation relative to reperfusion has differential effects on infarct size and cardiac function as assessed in mice by MRI. Am J Physiol Heart Circ Physiol 295: H2328-H2335, 2008. PMC2614530
Awad AS, Rouse M, Huang L, Vergis AL, Reutershan J, Cathro HP, Linden J and Okusa MD. Compartmentalization of neutrophils in the kidney and lung following acute ischemic kidney injury. Kidney Int 2009.
Alam MS, Kurtz CC, Rowlett RM, Reuter BK, Wiznerowicz E, Das S, Linden J, Crowe SE and Ernst PB. CD73 is expressed by human regulatory T helper cells and suppresses proinflammatory cytokine production and Helicobacter felis-induced gastritis in mice. J Infect Dis 199: 494-504, 2009.
Wilson JM, Ross WG, Agbai ON, Frazier R, Figler RA, Rieger J, Linden J and Ernst PB. The A2B adenosine receptor impairs the maturation and immunogenicity of dendritic cells. J Immunol 182: 4616-4623, 2009.
Wallace KL, Marshall MA, Ramos SI, Lannigan JA, Field JJ, Strieter RM and Linden J. NKT cells mediate pulmonary inflammation and dysfunction in murine sickle cell disease through production of IFN-g and CXCR3 chemokines. Blood, in press, 2009.
Patel RA, Glover DK, Broisat A, Kabul HK, Ruiz M, Goodman NC, Kramer CM, Meerdink DJ, Linden J and Beller GA. Reduction in Myocardial Infarct Size at 48 Hours after a Brief Intravenous Infusion of ATL-146e, a Highly Selective Adenosine A2A Receptor Agonist. Am J Physiol Heart Circ Physiol 2009.
Lappas CM, Liu PC, Linden J, Kang EM, and Malech HL. Adenosine A2A receptor activation limits graft-versus-host disease after allogenic hematopoietic stem cell transplantation. J Leukoc Biol, 2009.
Research Support
1 RC2HL101367-01 Linden,J.; Nathan,D. 12/1/09 – 11/30/14
NIH/NHLBI $500,000/yr
CTRIP: Treatment of Sickle Cell Crisis with inhibitors of NKT cell activation
This is a clinical trial of Lexiscan for sickle cell anemia
1 R01HL095704 (Linden, J) 12/1/09 – 6/3/13
NIH/NHLBI
Lymphocyte Activation in Sickle Cell Lung Disease
The goal of this proposal is to understand factors that contribute to leukocyte activation in Sickle Cell Disease.
U01 AI070491 (PI: Ernst, P) 08/15/06 – 07/31/11 0.5 CM effort
NIH/NIAID $756,082/yr 1 direct
Adenosine Receptor Agonists as an Immunotherapy for Biodefense
The goal of this project is to develop new compounds for the treatment of infections relevant to biodefense.
U01 AI075526 (PI: Guerrant, RL) 07/01/07 – 06/30/12 1
NIH/NIAID $600,000/yr (8%)
Tailoring Novel Therapeutics for Emerging Drug-Resistant C. Difficle Colitis
This is a partnership with Adenosine Therapeutics. This proposal is predicated on the observation that adenosine A2A agonists markedly reduce GI injury caused by C. Difficile Toxin. The goals are to delineate the molecular and cellular mechanisms underlying this protection and to advance a drug candidate toward clinical development.