Mircea Ivan

Mircea Ivan, MD, PhD

Associate Professor of Medicine

DOWNLOAD CV

Bio

 

We are interested in specific molecular responses to hypoxia and their relevance for cancer biology. My postdoctoral work in Dr. William Kaelin's laboratory elucidated the key signaling event that allows metazoan cells to monitor ambient O2 tension. In 2016 my first-author Science and PNAS papers were highlighted in connection to the annual Lasker Foundation awards.

 

In 2007 my group was the first to identify microRNAs induced by decreased oxygen tension, including miR-210, now widely recognized as universal “hypoxia-miR”. Hypoxia-regulated noncoding RNAs are integrated into our broader interest in metabolic responses to oxygen deprivation. 


We are developing new combinatorial therapeutic approaches based on rational interference with tumor metabolism, the main focus being on glioma and glioblastoma. In 2013 we generated proof of concept showing that blockade of pyruvate dehydrogenase kinase using dichloroacetate (DCA) significantly increases the efficacy of antiangiogenic agents in xenografts. With the support of IU Brain Tumor Working group, we continue to refine this strategy, aiming to open the road for clinical trials.


Since 2016 I have been serving as Senior Associate Editor for the Journal of Cellular and Molecular Medicine (Wiley, IF: 4.93).


 


 

 

 

Key Publications

 

  1. Ivan M, Kaelin WG Jr. The EGLN-HIF O(2)-Sensing System: Multiple Inputs and
    Feedbacks. Mol Cell. 2017 Jun 15;66(6):772-779. doi:10.1016/j.molcel.2017.06.002. Review. PubMed PMID: 28622522; PubMed Central PMCID: PMC5613951

  2. Brady LK, Wang H, Radens CM, Bi Y, Radovich M, Maity A, Ivan C, Ivan M, Barash
    Y, Koumenis C. Transcriptome analysis of hypoxic cancer cells uncovers intron
    retention in EIF2B5 as a mechanism to inhibit translation. PLoS Biol. 2017 Sep
    29;15(9):e2002623. doi: 10.1371/journal.pbio.2002623. eCollection 2017 Sep.
    PubMed PMID: 28961236

  3. Mantel CR, O’Leary HA,  Chitteti BR, Huang X, Cooper S, Hangoc G, Brustovetsky N, Srour EF, Lee MR, Messina-Graham S, Haas DM, Falah N, Kapur R, Pelus LM, Bardeesy N, Fitamant J, Ivan M, Kim K-S, Broxmeyer HE. Enhancing hematopoietic stem cell transplantation efficacy by mitigating oxygen shock. Cell 2015 Jun 9. pii: S0092-8674(15)00574-7. doi: 10.1016/j.cell.2015.04.054; PMID:26073944.

  4. Fishel ML, Wu X, Devlin CM, Logsdon DP, Jiang Y, Luo M, He Y, Yu Z, Tong Y, Lipking KP, Maitra A, Rajeshkumar NV, Scandura G, Kelley MR, Ivan M. Apurinic/Apyrimidinic Endonuclease/ Redox Factor-1 (APE1/Ref-1) Redox Function Negatively Regulates NRF2. J Biol Chem. 2015 Jan 30; 290(5):3057-68. doi:10.1074/jbc.M114.621995 pii: jbc.M114.621995 PMID: 25492865

  5. Ferdin J, Nishida N, Wu X, Nicoloso MS, Shah MY, Devlin C, Ling H, Shimizu M, Kumar K, Cortez MA, Ferracin M, Bi Y, Yang D, Czerniak B, Zhang W, Schmittgen TD, Voorhoeve MP, Reginato MJ, Negrini M, Davuluri RV, Kunej T, Ivan M, Calin GA. HINCUTs in Cancer: Hypoxia-Induced Non-Coding Ultraconserved Transcripts. Cell Death Differ, 2013 Dec;20(12):1675-87. doi: 10.1038/cdd.2013.119. PMID: 24037088; PMCID: PMC3824588

  6. Kumar K, Wigfield S, Gee HE, Devlin CM, Singleton D, Li JL,  Buffa F, Huffman M,  Sinn AL, Silver J, Turley H, Leek R, Harris AL, Ivan M. Dichloroacetate Reverses the Hypoxic Adaptation to Bevacizumab and Enhances its Antitumor Effects in Mouse Xenografts. J Mol Med, June 2013, 91(6): 749-758

  7. Devlin CM, Tim Lahm T, Hubbard WC, Van Demark M, Wang K, Wu X, Bielawska A, Obeid L, Ivan M, Petrache I. A Dihydroceramide-Based Response to Hypoxia. J Biol Chem, 2011 Nov 4;286(44):38069-78 PMID: 21914808; PMCID: PMC320748

  8. Kulshreshtha R, Ferracin M, Wojcik SE, Garzon R, Alder H, Agosto-Perez FJ, Davuluri R, Liu C-G, Croce CM, Negrini M, Calin GA, Ivan M. A MicroRNA Signature of Hypoxia. Mol. Cell. Biol. 2007 27(5):1859-67.

 

Connect


(317) 274-0322 


Hematology/Oncology
Joseph E. Walther Hall, Room C225 980 W. Walnut St.
Indianapolis , IN 46202


  

Cancer
Translational Research

Titles & Appointments

  • Associate Professor of Microbiology & Immunology