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Stanley Tahara, PhD

Title(s)Associate Professor of Molecular Microbiology & Immunology
Phone+1 323 442 1722
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    Our laboratory is interested in post-transcriptional regulation. Currently we study miRNA synthesis and function in the sickle cell disease model. Clinical consequences of this genetic illness lead to a spectrum of circulatory and respiratory symptoms originating from a single mutation of the beta-globin gene. In particular pulmonary hypertension results from the vascular occlusion caused by the abnormal red blood cell shape. This leads to expression of vasoactive cytokines and hormones which aggravate and prolong the original vascular insult. Plasminogen activator inhibitor-1 (SERPINE1) and endothelin 1 (EDN1) are two such cell modulators that are dysregulated in acute phases of the illness. We identified miRNAs which are responsible for reversing expression of both SERPINE1 and EDN1; more importantly, we examined in detail the transcriptional regulation and synthesis of these key miRNA mediators. This information has been useful in that we identified a potential pharmacologic therapy that induced specific miRNA expression for the purpose of reducing the expression of SERPINE1 and EDN1.

    The second area of interest examines the biological significance of protein arginine methylation of translation initiation factors. We are currently studying the effect of Arg362 methylation of factor eIF4A. The latter is the prototype of DEXD/H box nucleotide dependent helicases. We have found that methylation of Arg362 results in 1) significantly reduced ATPase activity and 2) inhibition of eIF4A assembly with eIF4G into the eIF4F heterotrimer. We believe this example of covalent modification is representative of a previously unknown regulatory circuit for modulating cellular protein synthesis. Our current efforts are directed towards identifying regulators of protein methylation and further examination of eIF4A with respect to mRNA specific effects in protein synthesis.

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    Collapse Research Activities and Funding
    TRANSLATIONAL CONTROL IN MHV-INFECTED CELLS
    NIH/NINDS R01NS030880Jan 1, 1994 - Dec 31, 1997
    Role: Principal Investigator
    REGULATORY ASPECTS OF EUKARYOTIC MRNA STRUCTURE
    NIH/NIGMS R01GM038512Aug 1, 1987 - Jul 31, 1991
    Role: Principal Investigator

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    Collapse Publications
    Publications listed below are automatically derived from MEDLINE/PubMed and other sources, which might result in incorrect or missing publications. Researchers can login to make corrections and additions, or contact us for help.
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    1. Kalra VK, Zhang S, Malik P, Tahara SM. Placenta growth factor mediated gene regulation in sickle cell disease. Blood Rev. 2018 01; 32(1):61-70. PMID: 28823762.
      View in: PubMed
    2. Chen CL, Huang JY, Wang CH, Tahara SM, Zhou L, Kondo Y, Schechter J, Su L, Lai MM, Wakita T, Cosset FL, Jung JU, Machida K. Hepatitis C virus has a genetically determined lymphotropism through co-receptor B7.2. Nat Commun. 2017 01 09; 8:13882. PMID: 28067225.
      View in: PubMed
    3. Li C, Zhou Y, Loberg A, Tahara SM, Malik P, Kalra VK. Activated Transcription Factor 3 in Association with Histone Deacetylase 6 Negatively Regulates MicroRNA 199a2 Transcription by Chromatin Remodeling and Reduces Endothelin-1 Expression. Mol Cell Biol. 2016 11 15; 36(22):2838-2854. PMID: 27573019.
      View in: PubMed
    4. Chen CL, Uthaya Kumar DB, Punj V, Xu J, Sher L, Tahara SM, Hess S, Machida K. NANOG Metabolically Reprograms Tumor-Initiating Stem-like Cells through Tumorigenic Changes in Oxidative Phosphorylation and Fatty Acid Metabolism. Cell Metab. 2016 Jan 12; 23(1):206-19. PMID: 26724859.
      View in: PubMed
    5. Gonsalves CS, Li C, Malik P, Tahara SM, Kalra VK. Peroxisome proliferator-activated receptor-a-mediated transcription of miR-301a and miR-454 and their host gene SKA2 regulates endothelin-1 and PAI-1 expression in sickle cell disease. Biosci Rep. 2015 Oct 12; 35(6). PMID: 26460070.
      View in: PubMed
    6. Gonsalves CS, Li C, Mpollo MS, Pullarkat V, Malik P, Tahara SM, Kalra VK. Erythropoietin-mediated expression of placenta growth factor is regulated via activation of hypoxia-inducible factor-1a and post-transcriptionally by miR-214 in sickle cell disease. Biochem J. 2015 Jun 15; 468(3):409-23. PMID: 25876995; PMCID: PMC4643367.
    7. Li C, Gonsalves CS, Eiymo Mwa Mpollo MS, Malik P, Tahara SM, Kalra VK. MicroRNA 648 Targets ET-1 mRNA and is cotranscriptionally regulated with MICAL3 by PAX5. Mol Cell Biol. 2015 Feb; 35(3):514-28. PMID: 25403488.
      View in: PubMed
    8. Li C, Mpollo MS, Gonsalves CS, Tahara SM, Malik P, Kalra VK. Peroxisome proliferator-activated receptor-a-mediated transcription of miR-199a2 attenuates endothelin-1 expression via hypoxia-inducible factor-1a. J Biol Chem. 2014 Dec 26; 289(52):36031-47. PMID: 25389292.
      View in: PubMed
    9. Ferreira R, Santos T, Amar A, Gong A, Chen TC, Tahara SM, Giannotta SL, Hofman FM. Argonaute-2 promotes miR-18a entry in human brain endothelial cells. J Am Heart Assoc. 2014 May 16; 3(3):e000968. PMID: 24837588.
      View in: PubMed
    10. Pullarkat V, Meng Z, Tahara SM, Johnson CS, Kalra VK. Proteasome inhibition induces both antioxidant and hb f responses in sickle cell disease via the nrf2 pathway. Hemoglobin. 2014; 38(3):188-95. PMID: 24670032.
      View in: PubMed
    11. Ferreira R, Santos T, Amar A, Tahara SM, Chen TC, Giannotta SL, Hofman FM. MicroRNA-18a improves human cerebral arteriovenous malformation endothelial cell function. Stroke. 2014 Jan; 45(1):293-7. PMID: 24203843.
      View in: PubMed
    12. Pham LK, Liang M, Adisetiyo HA, Liao CP, Cohen MB, Tahara SM, Frenkel B, Kasahara N, Roy-Burman P. Contextual effect of repression of bone morphogenetic protein activity in prostate cancer. Endocr Relat Cancer. 2013 Dec; 20(6):861-74. PMID: 24042462.
      View in: PubMed
    13. Patel N, Tahara SM, Malik P, Kalra VK. Involvement of miR-30c and miR-301a in immediate induction of plasminogen activator inhibitor-1 by placental growth factor in human pulmonary endothelial cells. Biochem J. 2011 Mar 15; 434(3):473-82. PMID: 21175428; PMCID: PMC3078570.
    14. Wooderchak WL, Zang T, Zhou ZS, Acuña M, Tahara SM, Hevel JM. Substrate profiling of PRMT1 reveals amino acid sequences that extend beyond the "RGG" paradigm. Biochemistry. 2008 Sep 09; 47(36):9456-66. PMID: 18700728.
      View in: PubMed
    15. Hsu YC, Acuña M, Tahara SM, Peng CA. Reduced phagocytosis of colloidal carriers using soluble CD47. Pharm Res. 2003 Oct; 20(10):1539-42. PMID: 14620504.
      View in: PubMed
    16. Nelson GW, Stohlman SA, Tahara SM. High affinity interaction between nucleocapsid protein and leader/intergenic sequence of mouse hepatitis virus RNA. J Gen Virol. 2000 Jan; 81(Pt 1):181-8. PMID: 10640556.
      View in: PubMed
    17. Ito T, Tahara SM, Lai MM. The 3'-untranslated region of hepatitis C virus RNA enhances translation from an internal ribosomal entry site. J Virol. 1998 Nov; 72(11):8789-96. PMID: 9765423.
      View in: PubMed
    18. Bergmann C, Dimacali E, Stohl S, Wei W, Lai MM, Tahara S, Marten N. Variability of persisting MHV RNA sequences constituting immune and replication-relevant domains. Virology. 1998 May 10; 244(2):563-72. PMID: 9601524.
      View in: PubMed
    19. Tahara SM, Dietlin TA, Nelson GW, Stohlman SA, Manno DJ. Mouse hepatitis virus nucleocapsid protein as a translational effector of viral mRNAs. Adv Exp Med Biol. 1998; 440:313-8. PMID: 9782298.
      View in: PubMed
    20. Williams-Hill DM, Duncan RF, Nielsen PJ, Tahara SM. Differential expression of the murine eukaryotic translation initiation factor isogenes eIF4A(I) and eIF4A(II) is dependent upon cellular growth status. Arch Biochem Biophys. 1997 Feb 01; 338(1):111-20. PMID: 9015395.
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    21. Stohlman SA, Hinton DR, Cua D, Dimacali E, Sensintaffar J, Hofman FM, Tahara SM, Yao Q. Tumor necrosis factor expression during mouse hepatitis virus-induced demyelinating encephalomyelitis. J Virol. 1995 Sep; 69(9):5898-903. PMID: 7637037.
      View in: PubMed
    22. Stohlman SA, Yao Q, Bergmann CC, Tahara SM, Kyuwa S, Hinton DR. Transcription and translation of proinflammatory cytokines following JHMV infection. Adv Exp Med Biol. 1995; 380:173-8. PMID: 8830475.
      View in: PubMed
    23. Kyuwa S, Cohen M, Nelson G, Tahara SM, Stohlman SA. Modulation of cellular macromolecular synthesis by coronavirus: implication for pathogenesis. J Virol. 1994 Oct; 68(10):6815-9. PMID: 8084020.
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    24. Tahara SM, Dietlin TA, Bergmann CC, Nelson GW, Kyuwa S, Anthony RP, Stohlman SA. Coronavirus translational regulation: leader affects mRNA efficiency. Virology. 1994 Aug 01; 202(2):621-30. PMID: 8030227.
      View in: PubMed
    25. Fernández-Checa JC, Yi JR, Garcia-Ruiz C, Knezic Z, Tahara SM, Kaplowitz N. Expression of rat liver reduced glutathione transport in Xenopus laevis oocytes. J Biol Chem. 1993 Feb 05; 268(4):2324-8. PMID: 8428906.
      View in: PubMed
    26. Tahara S, Bergmann C, Nelson G, Anthony R, Dietlin T, Kyuwa S, Stohlman S. Effects of mouse hepatitis virus infection on host cell metabolism. Adv Exp Med Biol. 1993; 342:111-6. PMID: 8209716.
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    27. Tahara SM, Dietlin TA, Dever TE, Merrick WC, Worrilow LM. Effect of eukaryotic initiation factor 4F on AUG selection in a bicistronic mRNA. J Biol Chem. 1991 Feb 25; 266(6):3594-601. PMID: 1995620.
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    28. Ou JH, Bao H, Shih C, Tahara SM. Preferred translation of human hepatitis B virus polymerase from core protein- but not from precore protein-specific transcript. J Virol. 1990 Sep; 64(9):4578-81. PMID: 2384923.
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    29. Darzynkiewicz E, Stepinski J, Ekiel I, Goyer C, Sonenberg N, Temeriusz A, Jin Y, Sijuwade T, Haber D, Tahara SM. Inhibition of eukaryotic translation by nucleoside 5'-monophosphate analogues of mRNA 5'-cap: changes in N7 substituent affect analogue activity. Biochemistry. 1989 May 30; 28(11):4771-8. PMID: 2548592.
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    30. Darzynkiewicz E, Stepinski J, Ekiel I, Jin Y, Haber D, Sijuwade T, Tahara SM. Beta-globin mRNAs capped with m7G, m2.7(2)G or m2.2.7(3)G differ in intrinsic translation efficiency. Nucleic Acids Res. 1988 Sep 26; 16(18):8953-62. PMID: 3174438.
      View in: PubMed
    31. Darzynkiewicz E, Ekiel I, Lassota P, Tahara SM. Inhibition of eukaryotic translation by analogues of messenger RNA 5'-cap: chemical and biological consequences of 5'-phosphate modifications of 7-methylguanosine 5'-monophosphate. Biochemistry. 1987 Jul 14; 26(14):4372-80. PMID: 2822090.
      View in: PubMed