Faculty

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Stanley Tahara, PhD
Associate Professor of Molecular Microbiology & Immunology
Molecular Microbiology and Immunology
HMR 510A 2011 Zonal Avenue Health Sciences Campus Los Angeles
+1 323 442 1722

Overview

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.

Publications

Placenta growth factor mediated gene regulation in sickle cell disease. Blood Rev. 2017 Aug 16. View in: PubMed

Hepatitis C virus has a genetically determined lymphotropism through co-receptor B7. 2. Nat Commun. 2017 Jan 09; 8:13882. View in: PubMed

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 Nov 15; 36(22):2838-2854. View in: PubMed

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. View in: PubMed

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). View in: PubMed

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. View in: PubMed

MicroRNA 648 Targets ET-1 mRNA and is cotranscriptionally regulated with MICAL3 by PAX5. Mol Cell Biol. 2015 Feb; 35(3):514-28. View in: PubMed

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. View in: PubMed

Argonaute-2 promotes miR-18a entry in human brain endothelial cells. J Am Heart Assoc. 2014 May 16; 3(3):e000968. View in: PubMed

MicroRNA-18a improves human cerebral arteriovenous malformation endothelial cell function. Stroke. 2014 Jan; 45(1):293-7. View in: PubMed

Proteasome inhibition induces both antioxidant and hb f responses in sickle cell disease via the nrf2 pathway. Hemoglobin. 2014; 38(3):188-95. View in: PubMed

Contextual effect of repression of bone morphogenetic protein activity in prostate cancer. Endocr Relat Cancer. 2013 Dec; 20(6):861-74. View in: PubMed

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. View in: PubMed

Substrate profiling of PRMT1 reveals amino acid sequences that extend beyond the "RGG" paradigm. Biochemistry. 2008 Sep 09; 47(36):9456-66. View in: PubMed

Reduced phagocytosis of colloidal carriers using soluble CD47. Pharm Res. 2003 Oct; 20(10):1539-42. View in: PubMed

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. View in: PubMed

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. View in: PubMed

Variability of persisting MHV RNA sequences constituting immune and replication-relevant domains. Virology. 1998 May 10; 244(2):563-72. View in: PubMed

Mouse hepatitis virus nucleocapsid protein as a translational effector of viral mRNAs. Adv Exp Med Biol. 1998; 440:313-8. View in: PubMed

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. View in: PubMed

Tumor necrosis factor expression during mouse hepatitis virus-induced demyelinating encephalomyelitis. J Virol. 1995 Sep; 69(9):5898-903. View in: PubMed

Transcription and translation of proinflammatory cytokines following JHMV infection. Adv Exp Med Biol. 1995; 380:173-8. View in: PubMed

Modulation of cellular macromolecular synthesis by coronavirus: implication for pathogenesis. J Virol. 1994 Oct; 68(10):6815-9. View in: PubMed

Coronavirus translational regulation: leader affects mRNA efficiency. Virology. 1994 Aug 01; 202(2):621-30. View in: PubMed

Expression of rat liver reduced glutathione transport in Xenopus laevis oocytes. J Biol Chem. 1993 Feb 05; 268(4):2324-8. View in: PubMed

Effects of mouse hepatitis virus infection on host cell metabolism. Adv Exp Med Biol. 1993; 342:111-6. View in: PubMed

Effect of eukaryotic initiation factor 4F on AUG selection in a bicistronic mRNA. J Biol Chem. 1991 Feb 25; 266(6):3594-601. View in: PubMed

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. View in: PubMed

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. View in: PubMed

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. View in: PubMed

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. View in: PubMed

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