Pedersen Lab

Principal Investigator: Irene Munk Pedersen, PhD  

Research Focus: Stem cells


Pedersen Lab: In-depth

The research interest of the Pedersen laboratory is based on the recent discovery of microRNAs (miRs), which has revolutionized our understanding of gene control. miRs play key roles in controlling development, stem cell fates and differentiation, and mutations in human miR genes have been linked to disease states. An important task is to unveil the functions of individual miRs, determine how the miRs themselves are regulated and elucidate their role in normal cell homeostasis and human disease.

The main focus of the Pedersen laboratory is to investigate the role of specific miRs (identified by anti-miR library screens) in normal cells (induced pluripotent stem cells (iPSCs) and cells derived from iPSC) and explore how to use miRs as tools to regulate/counteract potential dysregulation in neurological disorders and cancer. A second area of research interest of the lab is to evaluate miRs function as novel restriction factors of mobile elements and retrovirus (LINE-1, hERVs and HIV-1) in human cells.


Pedersen Lab Grants

Current

NIH R01 "miR regulation of the neurovasculature function in health and disease"

Completed Research Support (from NIH)

NIH K01 "Cooperation of PTEN and SHIP as tumor suppressors in B-cells"


Publications

  • Pedersen IM, Buhl AM, Klausen P, Geisler CH and Jurlander J., The chimeric anti-CD20 antibody Rituximab induces apoptosis in B-cell chronic lymphocytic leukemia cells though a p38 mitogen activated protein-kinase-dependent mechanism. Blood 2002; 99: 1314-1319.
  • Chu P, Deforce D., Pedersen IM, Kitada S., Reed JC., Kipps JC., Latent sensitivity to Fas-mediated apoptosis after CD40 ligation may explain activity of CD154 gene therapy in chronic lymphocytic leukemia., Proc Natl Acad Sci U S A. 2002,99:3854-9.
  • Pedersen IM, Kitada S, Leoni LM, Zapata JM, Karres J, Tsukada N, Kipps TJ, Choi YS, Bennet F, Reed JC. Protection of CLL B-cells by a follicular dendritic cell line is dependent on induction of Mcl-1. Blood, 2002, 100:1795-801.
  • Reed JC., Kitada S., Pedersen IM., Shimmer A., Dysregulation of apoptosis genes in hematopoietic malignancies. Oncogene, 2002, 21:3459-74
  • Pedersen IM, Kitada S, Schimmer, A, Kim Y, Zapata JM,  Charboneau L, Andreeff M, Bennet,F, Sporn M, Liotta LA, Kipps TJ and Reed JC. The triterpenoid CDDO induces apoptosis in refractory CLL B-cells, Blood, 2002, 100:2965-2972.
  • Boatright KM., Renatus M., Scott FL., Sperandio S., Shin H., Pedersen IM.,  Ricci JE., Idris WA., Sutherlin DP., Green DR. and Salvesen GS., A Unified Model for Apical Caspase Activation”, Mol. Cell., 2003, 11:529-41.
  • Schimmer A, Pedersen IM , Kitada S, Eksioglu-Demiralp E, Minden MD,  Pinto R, Mah K, Andreeff M, Youngsoo K., Suh WS and Reed JC. Functional blocks in Caspase activation pathways are common in leukemia and predict patient-response to induction chemotherapy, Cancer Research, 2003, 63:1242-8.
  • Schimmer AD., Pedersen IM., Minden MD., Reed JC., Bcl-2 and Apoptosis in Chronic Lymphocytic Leukemia, Curr. Treat. Options Oncol, 2003, 4:211-8.   
  • Schimmer AD.,   Walsh K., Pinilla C., Bonneau M., Wang Z., Krajewska M., Bonneau M., Pedersen IM., Kitada S., Scott FL., Bailly-Maitre B., Glinsky G., Scudiero D., Sausville E., Salvesen G., Nefzi A., Ostresh JM., Houghten RA., and Reed JC., Small-molecule antagonists of apoptosis-suppressor XIAP exhibit broad anti-tumor activity, Cancer Cell, 2004, 5:25-35.
  • Pedersen IM. and  Reed JC., Microenvironmental interactions and survival of CLL B-cells., Leuk Lymphoma, 2004, 45:2365-72.
  • Pedersen IM, Wieland S, Cheng G, Violinia S, Croce CM, Chisari FV & David M., Interferon modulation of cellular miRs as a novel anti-viral mechanism, Nature, 2007, 449:919-22.       
  • Pedersen IM & David M., microRNAs in the immune response, Cytokine, 2008, 43:391-4.
  • Pedersen IM, Otero D., Kao E., Miletec A, Hother S. Ralfkiaer E, Rickert RC, Gronbeck K, David M, Onco-miR-155 targets SHIP to promote TNFa-dependent growth of B cell lymphomas, EMBO Mol. Med., 2009, 1:288-295.
  • Costinean S, Sandhu SK, Pedersen IM, Tili E, Trotta R, Perrotti D, Ciarlariello D, Neviani P, Harb J, Kauffman LR, Shidham A, Croce CM., Ship and C/ebp{beta} are targeted by miR-155 in B cells of E{micro}-miR-155 transgenic mice., Blood, 2009, 114:1374-82
  • Miletic AV*, Anzelon-Mills A*, Omori S, Pedersen IM, Shin D, Ravetch JV, Bolland S, Morse S and Rickert R, Coordinate Suppression of B Cell Lymphoma by PTEN and SHIP Phosphatases, J. Exp. Med., 2010, 207:2407-20
  • Idica A, Thompson J, Munk Pedersen I and Kadandale P. 2015. Using Undergraduate Molecular Biology Labs to Discover Targets of miRNAs in Humans. CourceSource
  • Spitale RC, Plikus MV and Pedersen IM, 2015, The emerging functions of regulatory RNA species in skin stem cells and regeneration, Exp. Dermatology, 24:827-8. PMID:26309056
  • Hamdorf M, Idica A, Zisoulis DG, Gamelin L, Martin C, Sanders K, and Pedersen IM, 2015, miR-128 represses retrotransposition by directly binding to L1 RNA, Nat. Struct. Mol. Biol, 22:824-31, PMID:26367248
  • Pedersen IM and Zisoulis DG, 2016, Transposable elements and miRNA: Regulation of Genomic Stability and Plasticity, Mobile Genetic Elements, 6(3):e1175537. PMID:27511122
  • Riess M, Fuchs NV, Idica A, Hamdorf M, Flory E, Pedersen IM, König R. 2017, Interferons Induce Expression of SAMHD1 in Monocytes through Down-regulation of miR-181a and miR-30a. J Biol Chem. 292:264-277. PMID:27909056
  • Daugaard I*, Sander K*, Vittayarukskul K, Idica I, Krog J, Chow R, Mortazavi A, Hager H, Hansen LL and Pedersen IM, 2017. miR-151a induces partial EMT by regulating E-Cadherin, Oncogenesis, 6:e366. PMID:28759022
  • Idica A, Sevrioukov E, Zisoulis DG, Hamdorf M, Castuera YG, Mortazavi A, Kadandale P and Pedersen IM, microRNA miR-128 inhibits LINE-1 (L1) retrotransposition by downregulating the nuclear import factor TNPO1, 2017 J Biol Chem. doi: 10.1074/jbc.M117.807677. PMID:28974576
  • Guzman* H., Sanders* K., Boshnakien A, Idica A, Jury D., Daugaard I, Zisoulis DG, and Pedersen IM, 2018, miR-128 represses telomerase activity by directly targeting TERT mRNA, Oncotarget, 9:13244-13253. PMID: 29568354
  • Fung L, Guzman H, Sevrioukov E, Idica A, Park E, Bochnakian A, Daugaard I, Jury D, Mortazavi A, Zisoulis DG and Pedersen IM. 2019, miR-128 Restriction of LINE-1 (L1) Retrotransposition Is Dependent on Targeting hnRNPA1 mRNA, Int. J Mol. Sci., 20, pii: E1955. PMID:31010097
  • Bochnakian A, Zhen A, Zisoulis DG, Idica A, KewalRamani V, Neel N, Daugaard I, Hamdorf M, Kitchen S, Lee K, and Pedersen IM. 2019. Interferon-inducible miR-128 modulates HIV-1 replication by targeting TNPO3 mRNA, J. Virol. [Epub ahead of print]. PMID:31341054
  • Jury D., Daugaard I, Sander KJ, Hansen LL, Agalliu D and Pedersen IM, 2019, miR-151a enhances Slug dependent angiogenesis, Oncotarget, in press

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