Mircea Ivan, M.D., Ph.D.

Associate Professor of Medicine
Associate Professor of Microbiology and Immunology

Description and summary of research focus of the laboratory 

We aim to understand the role of specific microRNAs in the hypoxia response and in the progression of breast cancer. The current focus is on miR-210.  We have demonstrated that miR-210 is a direct target of Hypoxia Inducible Factors (HIFs), master regulators of the response to low oxygen, with critical roles in tumor formation. Importantly, miR-210 was found by multiple studies to be overexpressed in breast cancer, and its upregulation was recently associated with adverse prognosis and metastatic potential in breast cancer. We aim to mechanistically dissect the role of miR-210 in cell survival under stress, to identify critical miR-210 gene targets and develop animal models of breast cancer with altered level of miR-210. 

  • Gee HE, Ivan C, Calin GA, Ivan M. Hypoxamirs and Cancer: from Biology to Targeted Therapy. Antioxid Redox Signal. 2014; Sep 10;21(8):1220-38. doi: 10.1089/ars.2013.5639. (corresponding author); featured article.
  • Rupaimoole R, Wu S, Pradeep S, Ivan C, Pecot C, Gharpure K, Sidalaghatta Nagaraja A, Armaiz-Pena GN, Michael McGuire , Zand B, Dalton H, Filant J, Bottsford-Miller J, Lu C, Sadaoui N, Mangala LS, Taylor M, van den Beucken T, Koch E, Rodriguez-Aguayo C, Huang L, Bar-Eli M, Wouters B, Radovich M, Ivan M, Calin GA, Zhang W, Lopez-Berestein G, Sood AK. Hypoxia Mediated Downregulation of miRNA Biogenesis Promotes Tumor Progression. Nature Communications 2014 5:5202;  DOI: 10.1038/ncomms6202.
  • van den Beucken T, Koch E,  Chu K, Rupaimoole R, Prickaerts P, Adriaens M, Voncken JW, Harris AL, Buffa F, Haider S, Starmans M, Yao C, Ivan M, Ivan C, Pecot C, Boutros P, Sood AK, Koritzinsky M, Wouters B. Hypoxia promotes stem cell phenotypes and poor prognosis through epigenetic regulation of DICER. Nature Communications 2014 5:5202 DOI: 10.1038/ncomms6203.
  • 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. (joint-corresponding author).
  • 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 (corresponding author).
  • 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 (equal corresponding author).
  • Favaro E, Ramachandran A, McCormick R, Gee H, Blancher C, Crosby M, Devlin C, Blick C, Buffa F, Li J-L, Vojnovic B, Pires de Neves R, Glazer P, Iborra F, Ivan M, Ragoussis J, Harris AL. MicroRNA-210 Regulates Mitochondrial Free Radical Response to Hypoxia and Krebs Cycle in Cancer Cells by Targeting Iron Sulfur Cluster Protein ISCU. PLoS ONE 2010 Apr26 5(4): e10345; (joint-corresponding author).
  • Crosby ME, Kulshreshtha R, Ivan M, Glazer PM. microRNA Regulation of DNA Repair Gene Expression in Hypoxic Stress. Cancer Res. 2009; 1;69(3):1221-9 (joint-corresponding author). ISI-Highly cited
  • 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. Epub 2006 Dec 28. (corresponding author). ISI - Highly cited
  • Ivan M, Kondo K, Yang H, Kim W, Valiando J, Ohh M, Salic A, Asara JM, Lane WS, Kaelin WG. HIFalpha targeted for VHL-mediated destruction by proline hydroxylation: implications for O2 sensing. Science. 2001 Apr 20; 292 (5516): 464-8 (research article). ISI- Highly cited.

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  • 1994-1998:  Cardiff University School of Medicine (formerly University of Wales College of Medicine), Cardiff, United Kingdom
  • 1987-1993:  "Carol Davila" University of Medicine and Pharmacy, Bucharest, Romania (M.D. awarded 1993) 

Department of Microbiology and Immunology | IU School of Medicine | 635 Barnhill Drive, MS 420 | Indianapolis, IN 46202 | (317) 274-0506