Chercheur

    Richard L. Momparler , Ph.D.

    richard.l.momparler@umontreal.ca
    Richard L. Momparler
    Axe de recherche
    Maladies virales, immunitaires et cancers
    Thème de recherche
    Cancers : mécanismes génétiques et moléculaires et nouvelles thérapies
    Adresse
    CHUSJ - Centre de Recherche

    Téléphone
    514 345-4931 #6140

    Fax
    514 345-4801

    Titres

    • Professeur, Département de pharmacologie, Université de Montréal, 1985.
    • Chercheur, Centre de recherche CHU Sainte-Justine, 1977.

    Formation

    • Postdoctorat en biochimie, International Laboratory Genetics & Biophysics, Naples, Italie, 1966.
    • Postdoctorat en pharmacologie, Yale University, 1965.
    • PhD en pharmacologie, University of Vermont, 1964.
    • BSc en biologie, Michigan State University, 1957.

    Intérêts de recherche

    Les principaux intérêts de recherche de Richard Momparler ont trait à l’évaluation de divers agents expérimentaux dans la chimiothérapie du cancer. Richard Momparler a été le premier à dévoiler que le mécanisme d’action de l’Ara-C était d’agir comme terminateur de chaîne. Il a également été le premier à proposer une analyse raisonnée pour l’utilisation de l’Ara-C à fortes doses dans le traitement de la leucémie aiguë.

    Grâce à ses travaux de recherche sur un modèle de souris, il a découvert que l’aza-5-déoxycytidine (5-AZA) était un agent antileucémique plus puissant que l’Ara-C. En collaboration avec les hématologues du CHU Sainte-Justine et avec son équipe, il a été le premier à mener un essai clinique sur l’effet du 5-AZA chez les enfants atteints de leucémie et à démontrer que le 5-AZA était un médicament actif.

    Au cours de l’évolution du cancer, plusieurs gènes suppresseurs de tumeurs sont déactivés par la méthylation aberrante de l’ADN. Le laboratoire de Richard Momparler a été le premier à démontrer que la méthylation du récepteur de l’acide rétinoïque RARb désactivait les gènes suppresseurs de tumeurs dans le cancer du côlon et du sein chez l’humain.

    En collaboration avec Joseph Ayoub de l’Hôpital Notre-Dame, son équipe a réalisé un essai clinique sur l’effet du 5-AZA chez des patients atteints d’un cancer du poumon avancé et a mis en évidence son rôle de suppresseur de tumeurs actif. Plus récemment, l’équipe de Richard Momparler a examiné d’autres agents inhibiteurs de la désacétylation des histones pour utilisation en combinaison avec le 5-AZA. Les données actuelles suggèrent que ces inhibiteurs intéressants servent à augmenter l’activité antinéoplasique du 5-AZA et que l’utilisation du 5-AZA en combinaison avec ces agents serait efficace dans le cadre de futurs essais cliniques menés auprès de patients atteints de cancer.

    Sommaire de carrière

    • Professeur associé, Département de pharmacologie, Université de Montréal, 1977-1984.
    • Professeur associé, Département de pharmacologie, University of Southern California, Los Angeles, 1972-1976.
    • Professeur adjoint, Département de biochimie, Université McGill, 1967-1971.

Publications

Epigenetic action of decitabine (5-aza-2'-deoxycytidine) is more effective against acute myeloid leukemia than cytotoxic action of cytarabine (ARA-C) - Momparler RL, Côté S, Momparler LF. Epigenetic action of decitabine (5-aza-2'-deoxycytidine) is more effective against acute myeloid leukemia than cytotoxic action of cytarabine (ARA-C). Leukemia Res 2013; 37(8): 980-984.

Synergistic antileukemic action of a combination of inhibitors of DNA methylation and histone methylation - Momparler RL, Idaghdour Y, Marquez VE, Momparler LF. Synergistic antileukemic action of a combination of inhibitors of DNA methylation and histone methylation. Leukemia Res 2012; 36(8): 1049-1054.

A perspective on the comparison of antileukemic activity of 5-Aza-2'-deoxycytidine (Decitabine) and 5-Azacytidine (Vidaza) - Momparler RL. A perspective on the comparison of antileukemic activity of 5-Aza-2'-deoxycytidine (Decitabine) and 5-Azacytidine (Vidaza). Pharmaceuticals 2012; 5: 875-881.

3-deazauridine enhances the antileukemic action of 5-aza-2'-deoxycytidine and targets drug-resistance due to deficiency in deoxycytidine kinase - Raynal NJ-M, Momparler LF, Rivard G-É, Momparler RL. 3-deazauridine enhances the antileukemic action of 5-aza-2'-deoxycytidine and targets drug-resistance due to deficiency in deoxycytidine kinase. Leukemia Res 2011; 35(1): 110-118.

3-deazauridine enhances the antileukemic action of 5-aza-2'-deoxycytidine and targets drug-resistance due to deficiency in deoxycytidine kinase - Raynal NJ, Momparler LF, Rivard G-É, Momparler RL. 3-deazauridine enhances the antileukemic action of 5-aza-2'-deoxycytidine and targets drug-resistance due to deficiency in deoxycytidine kinase. Leukemia Res 2011; 35(1): 110-118.

Inhibition of cytidine deaminase by zebularine enhances the antineoplastic action of 5-aza-2'-deoxycytidine - Lemaire M, Momparler LF, Raynal NJ, Bernstein M, Momparler RL. Inhibition of cytidine deaminase by zebularine enhances the antineoplastic action of 5-aza-2'-deoxycytidine. Cancer Chemother Pharmacol 2009; 63(3): 411-416.

Synergistic effect of 5-Aza-2'-deoxycytidine and genistein in combination against leukemia. - Raynal NJ-M, Momparler LF, Charbonneau M, Momparler RL. Synergistic effect of 5-Aza-2'-deoxycytidine and genistein in combination against leukemia.. Oncol Res 2008; 17(5): 223-230.

Antileukemic activity of genistein, a major isoflavone present in soy products - Raynal NJ-M, Momparler LF, Charbonneau M, Momparler RL. Antileukemic activity of genistein, a major isoflavone present in soy products. J Nat Prod 2008; 71(1): 3-7.

Antileukemic activity of genistein, a major isoflavone present in soy products - Raynal NJ, Momparler LF, Charbonneau M, Momparler RL. Antileukemic activity of genistein, a major isoflavone present in soy products. J Nat Prod 2008; 71(1): 3-7.

Synergistic effect of 5-Aza-2'-deoxycytidine and genistein in combination against leukemia. - Raynal NJ, Momparler LF, Charbonneau M, Momparler RL. Synergistic effect of 5-Aza-2'-deoxycytidine and genistein in combination against leukemia.. Oncol Res 2008; 17(5): 223-230.

Preclinical evaluation of the antineoplastic action of 5-aza-2'-deoxycytidine (decitabine, dacogen) and different histone deacetylase inhibitors of human Ewing's sarcoma cells - Hurtubise A, Bernstein M, Momparler RL. Preclinical evaluation of the antineoplastic action of 5-aza-2'-deoxycytidine (decitabine, dacogen) and different histone deacetylase inhibitors of human Ewing's sarcoma cells. Cancer Cell Int 2008; 8: 16 (on line).

Importance of dose-schedule of 5-aza-2'-deoxycytidine for epigenetic therapy of cancer - Lemaire M, Chabot GG, Raynal NJ, Momparler LF, Hurtubise A, Bernstein M, Momparler RL. Importance of dose-schedule of 5-aza-2'-deoxycytidine for epigenetic therapy of cancer. BMC Cancer 2008; 8: 128.

Effect of histone deacetylase inhibitor LAQ824 on antineoplastic action of 5-Aza-2'-deoxycytidine (decitabine) on human breast carcinoma cells - Hurtubise A, Momparler RL. Effect of histone deacetylase inhibitor LAQ824 on antineoplastic action of 5-Aza-2'-deoxycytidine (decitabine) on human breast carcinoma cells. Cancer Chemother Pharmacol 2006; 58(5): 618-625.

Cleavage of intracellular hepatitis C RNA in the virus core protein region by deoxyribozymes - Trépanier J, Tanner J, Momparler RL, Le NLO, Alvarez F, Alfieri C. Cleavage of intracellular hepatitis C RNA in the virus core protein region by deoxyribozymes. J Viral Hepat 2006; 13(2): 131-138.

Pharmacology of 5-Aza-2'-deoxycytidine (decitabine) - Momparler RL. Pharmacology of 5-Aza-2'-deoxycytidine (decitabine). Semin Hematol 2005; 42(3 Suppl 2): S9-16.

Epigenetic therapy of cancer with 5-aza-2'-deoxycytidine (decitabine) - Momparler RL. Epigenetic therapy of cancer with 5-aza-2'-deoxycytidine (decitabine). Semin Hematol 2005; 32(5): 443-451.

Enhancement of antineoplastic action of 5-aza-2'-deoxycytidine by zebularine on L1210 leukemia - Lemaire M, Momparler LF, Bernstein M, Marquez VE, Momparler RL. Enhancement of antineoplastic action of 5-aza-2'-deoxycytidine by zebularine on L1210 leukemia. Anticancer Drugs 2005; 16: 301-308.

Evaluation of antineoplastic action of 5-aza-2'-deoxycytidine (Dacogen) and docetaxel (Taxotere) on human breast, lung and prostate carcinoma cell lines - Hurtubise A, Momparler RL. Evaluation of antineoplastic action of 5-aza-2'-deoxycytidine (Dacogen) and docetaxel (Taxotere) on human breast, lung and prostate carcinoma cell lines. Anticancer Drugs 2004; 15(2): 161-167.

Antineoplastic action of 5-aza-2'-deoxycytidine (Dacogen) and depsipeptide on Raji lymphoma cells - Shaker S, Bernstein M, Momparler RL. Antineoplastic action of 5-aza-2'-deoxycytidine (Dacogen) and depsipeptide on Raji lymphoma cells. Oncol Rep 2004; 11(6): 1253-1256.

Enhancement of antineoplastic action of 5-aza-2'-deoxycytidine by phenylbutyrate on L1210 leukemic cells - Lemaire M, Momparler LF, Farinha NJ, Bernstein M, Momparler RL. Enhancement of antineoplastic action of 5-aza-2'-deoxycytidine by phenylbutyrate on L1210 leukemic cells. Leuk Lymphoma 2004; 45(1): 147-154.

Action of troxacitabine on cells transduced with human cytidine deaminase cDNA - Boivin A-J, Gourdeau H, Momparler RL. Action of troxacitabine on cells transduced with human cytidine deaminase cDNA. Cancer Invest 2004; 22(1): 25-29.

Activation of expression of p15, p73 and E-cadherin in leukemic cells by different concentrations of 5-aza-2'-deoxycytidine (Decitabine) - Farinha NJ, Shaker S, Lemaire M, Momparler LF, Bernstein M, Momparler RL. Activation of expression of p15, p73 and E-cadherin in leukemic cells by different concentrations of 5-aza-2'-deoxycytidine (Decitabine). Anticancer Res 2004; 24(1): 75-78.

Cancer epigenetics - Momparler RL. Cancer epigenetics. Oncogene 2003; 22(42): 6479-6483.

Preclinical evaluation of antineoplastic activity of inhibitors on DNA methylation (decitabine) and histone deacetylation (trichostatin A, depsipeptide) in combination against myeloid leukemia cells - Shaker S, Bernstein M, Momparler LF, Momparler RL. Preclinical evaluation of antineoplastic activity of inhibitors on DNA methylation (decitabine) and histone deacetylation (trichostatin A, depsipeptide) in combination against myeloid leukemia cells. Leukemia Res 2003; 27(15): 437-444.

Synergistic antineoplastic action of DNA methylation inhibitor 5-aza-2'-deoxycytidine and histone deacetylase inhibitor depsipeptide on human breast carcinoma cells - Primeau M, Gagnon J, Momparler RL. Synergistic antineoplastic action of DNA methylation inhibitor 5-aza-2'-deoxycytidine and histone deacetylase inhibitor depsipeptide on human breast carcinoma cells. Int J Cancer 2003; 103(2): 177-184.

Interaction of 5-aza-2'-deoxycytidine and depsipeptide on antineoplastic activity and activation of sigma 14-3-3, E-cadherin and TIMP3 expression in human breast carcinoma cells - Gagnon J, Shaker S, Primeau M, Hurbutise A, Momparler RL. Interaction of 5-aza-2'-deoxycytidine and depsipeptide on antineoplastic activity and activation of sigma 14-3-3, E-cadherin and TIMP3 expression in human breast carcinoma cells. Anticancer Drugs 2003; 14(3): 193-202.

Antineoplastic action of 5-aza-2'-deoxycytidine and phenylbutyrate on human lung cancer - Boivin A-J, Momparler LF, Hurbutise A, Momparler RL. Antineoplastic action of 5-aza-2'-deoxycytidine and phenylbutyrate on human lung cancer. Anticancer Drugs 2002; 13(8): 1-6.

Cytotoxic activity of 2('),2(')-difluorodeoxycytidine, 5-aza-2(')-deoxycytidine and cytosine arabinoside in cells transduced with deoxycytidine kinase gene - Beauséjour C, Gagnon J, Primeau M, Momparler RL. Cytotoxic activity of 2('),2(')-difluorodeoxycytidine, 5-aza-2(')-deoxycytidine and cytosine arabinoside in cells transduced with deoxycytidine kinase gene. Biochem Biophys Res Commun 2002; 293(5): 1478-1484.

Human cytidine deaminase as an ex vivo drug selectable marker in gene-modified primary bone marrow stromal cells - Eliopoulos N, Al-Khaldi A, Beauséjour CM, Momparler RL, Momparler LF, Galipeau J. Human cytidine deaminase as an ex vivo drug selectable marker in gene-modified primary bone marrow stromal cells. Gene Ther 2002; 9(7): 452-462.

Potential of 5-aza-2'-deoxycytidine (Decitabine) a potent inhibitor of DNA methylation for therapy of advanced non-small cell lung cancer - Momparler RL, Ayoub J. Potential of 5-aza-2'-deoxycytidine (Decitabine) a potent inhibitor of DNA methylation for therapy of advanced non-small cell lung cancer. Lung Cancer 2001; 34(4): S111-S115.

Antineoplastic action and expression of retinoic acid receptor ß gene in breast carcinoma cells treated with 5-aza-2'-deoxycytidine and an histone deacetylase inhibitor - Bovenzi V, Momparler RL. Antineoplastic action and expression of retinoic acid receptor ß gene in breast carcinoma cells treated with 5-aza-2'-deoxycytidine and an histone deacetylase inhibitor. Cancer Chemother Pharmacol 2001; 48(1): 71-76.

Selection of drug-resistant transduced cells with cytosine nucleoside analogs using human cytidine deaminase gene - Beauséjour C, Eliopoulos N, Momparler LF, Le NLO, Momparler RL. Selection of drug-resistant transduced cells with cytosine nucleoside analogs using human cytidine deaminase gene. Cancer Gene Ther 2001; 8(9): 669-676.

DNA methylation and cancer - Momparler RL, Bovenzi V. DNA methylation and cancer. J Cell Physiol 2000; 183: 145-154.

Quantitation of the inhibition of DNA methylation of retinoic acid receptors b gene by 5-aza-2'-deoxycytidine in tumor cells using single nucleotide primer extension assay - Bovenzi V, Momparler RL. Quantitation of the inhibition of DNA methylation of retinoic acid receptors b gene by 5-aza-2'-deoxycytidine in tumor cells using single nucleotide primer extension assay. Anal Biochem 2000; 281(1): 55-61.

Chemoprotection against nucleoside analogs using the human cytidine deaminase gene. Marrow protection: transduction of hematopoietic - Eliopoulos N, Beauséjour C, Momparler RL. Chemoprotection against nucleoside analogs using the human cytidine deaminase gene. Marrow protection: transduction of hematopoietic. Dans: Bertino JR (ed). Progress in Experimental Tumor Research. 2000; 124-142.

Evaluation of an inhibitor of DNA methylation, 5-aza-'2-deoxycytidine, for the treatment of lung cancer and the future role of gene therapy - Eliopoulos N, Beauséjour C, Ayoub J, Momparler RL. Evaluation of an inhibitor of DNA methylation, 5-aza-'2-deoxycytidine, for the treatment of lung cancer and the future role of gene therapy. Dans: Habib, NA (ed). Cancer Gene Therapy: Past Achievements and the Future Challenges. Londres. Kluwer Academic / Plenum Publishers, 2000; 433-446.

Potential of ribozymes against deoxycytidine kinase to confer drug resistance to cytosine nucleoside analogs - Beauséjour C, Tremblay G, Momparler RL. Potential of ribozymes against deoxycytidine kinase to confer drug resistance to cytosine nucleoside analogs. Biochem Biophys Res Commun 2000; 278: 569-575.

Coexpression of rat glutathione S-transferase A3 and human cytidine deaminase by a bicustronic retroviral vector confers in vitro resistance to nitrogen mustards and cytosine arabinoside in murine fibroblasts - Létourneau S, Palerme JS, Beauséjour C, Delisle JS, Momparler RL, Cournoyer D. Coexpression of rat glutathione S-transferase A3 and human cytidine deaminase by a bicustronic retroviral vector confers in vitro resistance to nitrogen mustards and cytosine arabinoside in murine fibroblasts. Cancer Gene Ther 2000; 7(5): 757-765.

Gene amplification of human cytidine deaminase proviral cDNA and increased levels of its mRNA produces enhanced drug resistance to cytosine arabinoside in retroviral-transduced murine fibroblasts - Beauséjour C, Momparler RL. Gene amplification of human cytidine deaminase proviral cDNA and increased levels of its mRNA produces enhanced drug resistance to cytosine arabinoside in retroviral-transduced murine fibroblasts. Cancer Lett 1999; 135: 29-36.

DNA methylation of the retinoic acid receptor beta gene in breast cancer and possible therapeutic role of 5'-aza-2'-deoxycytidine - Bovenzi V, Le NLO, Côté S, Sinnett D, Momparler LF, Momparler RL. DNA methylation of the retinoic acid receptor beta gene in breast cancer and possible therapeutic role of 5'-aza-2'-deoxycytidine. Anticancer Drugs 1999; 10: 471-476.

Drug resistance to 5'aza-2'-deoxycytidine, 2,2'-difluorodeoxycytidine and cytosine arabinoside conferred by retroviral-mediated transfer of human cytidine deaminase cDNA into muring cells - Eliopoulos N, Momparler RL. Drug resistance to 5'aza-2'-deoxycytidine, 2,2'-difluorodeoxycytidine and cytosine arabinoside conferred by retroviral-mediated transfer of human cytidine deaminase cDNA into muring cells. Cancer Chemother Pharmacol 1998; 42: 373-378.

Effect of 5'-aza-2'-deoxycydine and vitamine D3 analogs on growth and differenciation of human myeloid leukemic cells - Doré BT, Momparler RL. Effect of 5'-aza-2'-deoxycydine and vitamine D3 analogs on growth and differenciation of human myeloid leukemic cells. Cancer Chemother Pharmacol 1998; 41: 274-280.

Coexpression of cytidine deaminase and mutant dihydrofolade by a bicistronic retroviral vector confers resistance to cytosine arabinoside and methotrexate - Beauséjour C, Oanh NLO, Létourneau S, Cournoyer D, Momparler RL. Coexpression of cytidine deaminase and mutant dihydrofolade by a bicistronic retroviral vector confers resistance to cytosine arabinoside and methotrexate. Hum Gene Ther 1998; 9: 2537-2544.

Retroviral transfer and long term expression of human cytidine deaminase cDNA in hematopoietic cells following transplantation in mice - Eliopoulos N, Bovenzi V, Le NLO, Momparler LF, Greenbaum M, Létourneau S, Cournoyer D, Momparler RL. Retroviral transfer and long term expression of human cytidine deaminase cDNA in hematopoietic cells following transplantation in mice. Gene Ther 1998; 5: 1545-1551.

Demethylation by 5'-aza-2'-deoxycytidine of specific 5-methylcytosine sites in the promoter region of the retinoic acid receptor beta in human colon carcinoma cells - Côté S, Sinnett D, Momparler RL. Demethylation by 5'-aza-2'-deoxycytidine of specific 5-methylcytosine sites in the promoter region of the retinoic acid receptor beta in human colon carcinoma cells. Anticancer Drugs 1998; 9: 743-750.

Pilot phase I-II study on 5-Aza-2'-deoxycytidine (Decitabine) in patients with metastatic lung cancer - Momparler RL, Bouffard DY, Momparler LF, Dionne J, Bélanger K, Ayoub J. Pilot phase I-II study on 5-Aza-2'-deoxycytidine (Decitabine) in patients with metastatic lung cancer. Anticancer Drugs 1997; 8: 358-368.

Pharmacological approach for optimization of the dose-schedule of 5-Aza-2'-deoxycytidine (Decitabine) for the therapy of leukemia - Momparler RL, Côté S, Eliopoulos N. Pharmacological approach for optimization of the dose-schedule of 5-Aza-2'-deoxycytidine (Decitabine) for the therapy of leukemia. Leukemia 1997; 11: 175-180.

Activation of the retinoic acid receptor beta gene by 5-aza-2'-deoxycytidine in human DLD-1 colon carcinoma cells - Côté S, Momparler RL. Activation of the retinoic acid receptor beta gene by 5-aza-2'-deoxycytidine in human DLD-1 colon carcinoma cells. Anticancer Drugs 1997; 8: 56-61.

Resistance to cytosine arabinoside by retroviral-mediated gene transfer of human cytidine deaminase into murine fibroblast and hematopoietic cells - Momparler RL, Eliopoulos N, Bovenzi V, Létourneau S, Greenbaum M, Cournoyer D. Resistance to cytosine arabinoside by retroviral-mediated gene transfer of human cytidine deaminase into murine fibroblast and hematopoietic cells. Cancer Gene Ther 1996; 3: 331-338.

Transfection of murine fibroblast cells with human cytidine deaminase cDNA confers resistance to cytosine arabinoside - Momparler RL, Laliberté J, Eliopoulos N, Beauséjour C, Cournoyer D. Transfection of murine fibroblast cells with human cytidine deaminase cDNA confers resistance to cytosine arabinoside. Anticancer Drugs 1996; 7: 266-274.

Mutation in the ligand-binding domain of the retinoic acid receptor alpha in HL-60 leukemic cells resistant to retinoic acid and with increased sensitivity to vitamin D3 analogs - Doré BT, Momparler RL. Mutation in the ligand-binding domain of the retinoic acid receptor alpha in HL-60 leukemic cells resistant to retinoic acid and with increased sensitivity to vitamin D3 analogs. Leukemia Res 1996; 20: 761-769.

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