NARENDRAN, ARU - University of Calgary - Department of Biochemistry & Molecular Biology

个人简介

M.D. (Doctor of Medicine) Ph.D. (Doctor of Philosophy)

研究领域

Acute lymphoblastic leukemia is the most common pediatric malignancy, constituting more than 25% of all childhood cancers. Although cure rates have improved greatly, approximately one in five children relapse and survival rates post relapse are very low. Given this, more effective and innovative therapeutic strategies are urgently needed in order to improve prognosis. Aurora kinases, a family of serine/threonine kinases essential for regulated mitotic cell division, have been identified as potential targets for cancer therapeutics. These proteins are involved in regulation of several mitotic processes including centromere duplication, formation of a bipolar mitotic spindle, chromosome alignment on the mitotic spindle and fidelity monitoring of the spindle checkpoint, among others. Elevated expression of Aurora kinases has been identified in several primary tumours types and is associated with aneuploidy and alterations in chromosomal structure. Since Aurora kinases are overexpressed in many forms of cancer and are involved in mitotic control and genomic instability, it is hypothesized that these kinases are promising therapeutic targets. Based on this, the overall aim of this research project is to define the role of Aurora kinase inhibition as an effective therapeutic approach for the treatment of refractory pediatric leukemia. Specifically, the objectives of this project include determining the incidence and activity of Aurora kinases in pediatric leukemia, conducting cytotoxicity studies to evaluate the effect of Aurora kinase inhibition in vitro, identifying drug combinations that display synergistic activity with Aurora kinase inhibition and evaluating in vivo activity of Aurora kinase inhibition in murine xenograft models of pediatric leukemia.

近期论文

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Steele M and Narendran A. Mechanisms of Defective Erythropoiesis and Anemia in Pediatric Acute Lymphoblastic Leukemia (ALL). Ann Hematol. 2012 Apr 29. [Epub ahead of print]. de Oliveira C, Brassesco MS, Scrideli CA, Tone LG and Narendran A. MicroRNA Expression and Activity in Pediatric Acute Lymphoblastic Leukemia (ALL). Pediatric Blood and Cancer. 2012 Apr 10. doi: 10.1002/pbc.24167. [Epub ahead of print]. Lee C, Fotovati A, Triscott J, Chen J, Venugopal C, Singhal A, Dunham C, Kerr JM, Verreault M, Yip S, Wakimoto H, Jones C, Jayanthan A, Narendran A, Singh SK, Dunn SE. Polo-Like Kinase 1 (PLK1) Inhibition Kills Glioblastoma Multiforme Brain Tumour Cells in Part Through Loss of SOX2 and Delays Tumour Progression in Mice. Stem Cells. 2012. 30(6):1064-75 Mineyko A, Narendran A, Fritzler M, B. Comm, Wei, X-C, Schmeling H and Kirton A. Inflammatory biomarkers of pediatric focal cerebral arteriopathy. In press. Neurology. 2012. Jayanthan A, Bernoux D, Bose P, Riabowol K, Narendran A. Multi-tyrosine kinase inhibitors in preclinical studies for pediatric CNS AT/RT: Evidence for synergy with Topoisomerase-I inhibition. Cancer Cell Int. 2011. 29;11(1):44-55. Banderali U, Belke D, Singh A, Jayanthan A, Giles WR, Narendran A. Curcumin Blocks Kv11.1 (erg) Potassium Current and Slows Proliferation in the Infant Acute Monocytic Leukemia Cell line THP-1. Cell Physiol Biochem. 2011. 28(6):1169-80. Maddigan A, Truitt L, Arsenault R, Freywald T, Allonby O, Dean J, Narendran A, Xiang J, Weng A, Napper S, Freywald A. EphB Receptors Trigger Akt Activation and Suppress Fas Receptor-Induced Apoptosis in Malignant T Lymphocytes. J Immunol. 2011. 1;187(11):5983-94. Baderali U, Jayanthan A, Hoeksma K, Narendran A, Giles, W. Ion channels in pediatric CNS Atypical Teratoid/Rhabdoid Tumor (AT/RT) cells: potential targets for novel therapeutic agents. J Neurooncol. 2011. 107(1):111-9. Hoeksema KA, Jayanthan A, Cooper T, Gore L, Trippett T, Boklan J, Arceci RJ, Narendran A. Systematic in-vitro evaluation of the NCI/NIH Developmental Therapeutics Program Approved Oncology Drug Set for the identification of a candidate drug repertoire for MLL-rearranged leukemia. Onco Targets Ther. 2011. 4:149-68. Mummery A, Narendran A, Lee KY. Targeting Epigenetics through Histone Deacetylase Inhibitors in Acute Lymphoblastic Leukemia. Curr Cancer Drug Targets. 2011. 11(7):882-93. Singh A, Jayanthan A, Farran A, Elwi AN, Kim SW, Farran P, Narendran A. Induction of apoptosis in pediatric acute lymphoblastic leukemia (ALL) cells by the therapeutic opioid methadone and effective synergy with Bcl-2 inhibition. Leuk Res. 2011. 35(12):1649-57. Jayanthan A, Incoronato A, Blackmore C, Bernoux D, Lewis VA, Stam R, Whitlock JA and A. Narendran, Cytotoxicity, Drug Combinability, and Biological Correlates of ABT-737 Against Acute Lymphoblastic Leukemia Cells with MLL Rearrangement. Pediatr Blood Cancer. 2011 Mar;56(3):353-60. Koro K, Parkin, S, Yang, A, Narendran A, Egan C and A. Magliocco. Interactions between breast cancer cells and bone marrow derived cells in vitro define a role for Osteopontin in affecting breast cancer cell migration. Breast Cancer Research and Treatment. 2011 Feb;126(1):73-83. Blackmore C, Jayanthan A, Ujack E, Magliocco A, Narendran A. Analysis of multiple growth regulatory proteins using dissociable staining antibody arrays on solid tumor biopsy specimens. Fetal and Pediatric Pathology. Fetal Pediatr Pathol. 2011 Feb;30(3):177-88. Miettunen, P. Narendran, A. Jayanthan, A, Behrens and E Cron, R Successful treatment of severe pediatric rheumatic disease associated macrophage activation syndrome with IL-1 inhibition following conventional immunosuppressive therapy. Rheumatology (Oxford). 2011 Feb;50(2):417-9. Sooriyaarachchi M, Narendran A and Gailer J. Comparative hydrolysis and plasma protein binding of cis-platin and carboplatin in human plasma in vitro. Royal Society of Chemistry Journal, Metallomics. 2011 Jan;3(1):49-55. Blackmore C, Coppes MJ and Narendran A. A Review of Candidate Genes and Potential Targets for Therapeutics in Wilms tumor. Clin Transl Oncol. 2010 Sep;12(9):597-605. Ho, J. Leung, A. Narendran, A. Obesity as a Complication of Cancer in Children. In Overweightness and Walking. Editors: Caleb I. Black. Nova Scientific Publishers. NY . Sept. 2010. Horton TM, Sposto R, Brown P, Reynolds CP, Hunger SP, Winick NJ, Raetz EA, Carroll WL, Arceci RJ, Borowitz MJ, Gaynon PS, Gore L, Jeha S, Maurer BJ, Siegel SE, Biondi A, Kearns PR, Narendran A, Silverman LB, Smith MA, Zwaan CM, Whitlock JA. Toxicity assessment of molecularly targeted drugs incorporated into multiagent chemotherapy regimens for pediatric acute lymphoblastic leukemia (ALL): Review from an international consensus conference. Pediatric Blood and Cancer. Jul 1;54(7):872-8., 2010. Jayanthan A, Mittunen P, Incoronato A, Ortiz C, Anderson R, Lewis VA and A Narendran. Childhood Acute Lymphoblastic Leukemia (ALL) in Children Presenting with Severe Osteolysis: A model to study leukemia –bone interactions and potential targeted therapeutics. Pediatric Hematology Oncology. 2010 Apr;27(3):212-27.