CBG Faculty

Stanley Tahara, PhD
Stanley Tahara, PhD
Associate Professor of Molecular Microbiology & Immunology
Molecular Microbiology and Immunology
HMR 510A 2011 Zonal Avenue Health Sciences Campus Los Angeles
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.

Placenta growth factor mediated gene regulation in sickle cell disease Blood Rev. 2018 Jan; 32(1):61-70. . View in PubMed

Hepatitis C virus has a genetically determined lymphotropism through co-receptor B72. Nat Commun. 2017 Jan 09; 8:13882. . View in PubMed

Hepatitis C virus has a genetically determined lymphotropism through co-receptor B72. Nat Commun. 2017 01 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

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. . 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

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

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

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