MAHONEY, DOUG - University of Calgary - Department of Biochemistry & Molecular Biology

研究领域

Based on very promising phase I-II clinical data, several oncolytic viruses have recently been approved for late stage evaluation in human cancer patients. As such, these agents may soon provide an exciting alternative to drug-based therapies for some cancers. Non-pathogenic oncolytic viruses distinguish tumor from normal because of cancer-specific genetic defects, and often lead to long-term cures in previously resistant preclinical cancer models. My lab studies the interactions between oncolytic viruses (OV) and mammalian host tumor cells and normal inflammatory and immune cells in the tumor microenvironment. The short-term goals of my research program are to: (1) interrogate cancer genomes for opportunities to improve virus spread and induce bystander killing in tumors and (2) probe the tumor microenvironment for opportunities to enhance virus-induced tumor targeting by the host's immune system. In the long-term, my vision is to develop and test novel oncolytic and adjunctive therapeutics, primarily for solid tumors of brain, neuroendocrine and soft-tissue origin.

近期论文

查看导师新发文章（温馨提示：请注意重名现象，建议点开原文通过作者单位确认）

Mahoney DJ, Stojdl DF. Molecular pathways: multimodal cancer-killing mechanisms employed by oncolytic vesiculoviruses. Clin Cancer Res. 2013 Feb 15;19(4):758-63. Mahoney DJ, Stojdl DF. Functional genomic screening to enhance oncolytic virotherapy. Br J Cancer. 2013 Feb 5;108(2):245-9. Brun J, Mahoney DJ, Le Boeuf F, Lefebvre C, Sanaei CA, Falls T, Mccart JA, Stojdl DF.Oncolytic Vaccinia virus safely and effectively treats skin tumors in mouse models of xeroderma pigmentosum. Int J Cancer. 2013 Feb 1;132(3):726-31. Mahoney DJ, Stojdl DF. Fighting fire with fire: rewiring tumor cells for oncolytic virotherapy. Future Oncol. 2012 Mar;8(3):219-21 Mahoney DJ, Lefebvre C, Allan K, Brun J, Sanaei CA, Baird S, Pearce N, Grönberg S, Wilson B, Prakesh M, Aman A, Isaac M, Mamai A, Uehling D, Al-Awar R, Falls T, Alain T, Stojdl DF. Virus-tumor interactome screen reveals ER stress response can reprogram resistant cancers for oncolytic virus-triggered caspase-2 cell death. Cancer Cell. 2011 Oct 18;20(4):443-56. Mahoney DJ, Swales C, Athanasou NA, Bombardieri M, Pitzalis C, Kliskey K, Sharif M, Day AJ, Milner CM, Sabokbar A. TSG-6 inhibits osteoclast activity via an autocrine mechanism and is functionally synergistic with osteoprotegerin. Arthritis Rheum. 2011 Apr;63(4):1034-43 Mahoney DJ, Stojdl DF. Potentiating oncolytic viruses by targeted drug intervention. Curr Opin Mol Ther. 2010 Aug;12(4):394-402. Mahoney DJ, Stojdl DF. A call to arms: using RNAi screening to improve oncolytic viral therapy. Cytokine Growth Factor Rev. 2010 Apr-Jun;21(2-3):161-7 Cheung HH, Mahoney DJ, Lacasse EC, Korneluk RG. Down-regulation of c-FLIP Enhances death of cancer cells by smac mimetic compound. Cancer Res. 2009 Oct 1;69(19):7729-38. Zarnegar BJ, Wang Y, Mahoney DJ, Dempsey PW, Cheung HH, He J, Shiba T, Yang X, Yeh WC, Mak TW, Korneluk RG, Cheng G. Noncanonical NF-kappaB activation requires coordinated assembly of a regulatory complex of the adaptors cIAP1, cIAP2, TRAF2 and TRAF3 and the kinase NIK. Nat Immunol. 2008 Dec;9(12):1371-8. LaCasse EC, Mahoney DJ, Cheung HH, Plenchette S, Baird S, Korneluk RG. IAP-targeted therapies for cancer. Oncogene. 2008 Oct 20;27(48):6252-75 Mahoney DJ, Cheung HH, Mrad RL, Plenchette S, Simard C, Enwere E, Arora V, Mak TW, Lacasse EC, Waring J, Korneluk RG. Both cIAP1 and cIAP2 regulate TNFalpha-mediated NF-kappaB activation. Proc Natl Acad Sci U S A. 2008 Aug 19;105(33):11778-83. Mahoney DJ, Mikecz K, Ali T, Mabilleau G, Benayahu D, Plaas A, Milner CM, Day AJ, Sabokbar A. TSG-6 regulates bone remodeling through inhibition of osteoblastogenesis and osteoclast activation. J Biol Chem. 2008 Sep 19;283(38):25952-62. Cheung HH, Plenchette S, Kern CJ, Mahoney DJ, Korneluk RG. The RING domain of cIAP1 mediates the degradation of RING-bearing inhibitor of apoptosis proteins by distinct pathways. Mol Biol Cell. 2008 Jul;19(7):2729-40. Mahoney DJ, Safdar A, Parise G, Melov S, Fu M, MacNeil L, Kaczor J, Payne ET, Tarnopolsky MA. Gene expression profiling in human skeletal muscle during recovery from eccentric exercise. Am J Physiol Regul Integr Comp Physiol. 2008 Jun;294(6):R1901-10. Kuznetsova SA, Mahoney DJ, Martin-Manso G, Ali T, Nentwich HA, Sipes JM, Zeng B, Vogel T, Day AJ, Roberts DD. TSG-6 binds via its CUB_C domain to the cell-binding domain of fibronectin and increases fibronectin matrix assembly. Matrix Biol. 2008 Apr;27(3):201-10

个人简介

研究领域

近期论文