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College of Arts & Sciences
Department of Biological Sciences


Graduate Student Directory

Evelyn Chukwurah

Degree Program: Molecular, Cellular, and Developmental Biology
Email: chukwura@email.sc.edu
Room: CLS 507
Major Professor: Dr. Rekha Patel

Research interests

Eukaryotic cells engage a signaling pathway known as the Integrated Stress Response (ISR) to mount an appropriate response to a diverse range of stressful cellular conditions. A key component of the ISR is the attenuation of general protein synthesis through the phosphorylation of the alpha subunit of the eukaryotic initiation factor, eIF2 (eIF2α). Four dedicated serine-threonine protein kinases (GCN2- general control nonderepressible 2, HRI – Heme-Regulated Inhibitor, PERK – PKR like ER Kinase, and PKR – Protein Kinase R) each phosphorylate eIF2α in response to specific cellular stressors.

The interferon-inducible eIF2α kinase PKR is activated by dsRNA generated during viral infection. This interaction induces a conformational change that exposes an ATP binding site, which results in PKR’s trans-autophosphorylation, activation and subsequent eIF2α activation. PKR is also activated in response to ER stress, oxidative stress, serum deprivation, and heat shock through its interaction with its cellular activator, PACT (Protein Activator of PKR). PACT, which is constitutively phosphorylated at S246, is phosphorylated at S287 during stress. This second phosphorylation event increases PACT-PACT homodimer formation as well as PACT-PKR heterodimer formation, inducing the same conformational change that results in PKR activation.

PKR‘s activity is inhibited by its interaction with the RISC-associated protein, TRBP (TAR RNA Binding Protein). During viral infection and the previously mentioned stressful conditions, TRBP interacts with PKR and dsRNA in the former and with PKR and PACT in the latter, precluding interactions between dsRNA or PACT and PKR, and consequently PKR activation.

My current research interests involve elucidating how stress-induced post-translational modifications of TRBP affect its ability to efficiently inhibit PKR, and the mechanisms by which PKR is inhibited during HIV infection through the formation of a PKR inhibitory complex consisting PACT, ADAR1 (Adenosine Deaminase Acting on RNA 1), and the viral transactivator Tat.

Education

Lee University. B.Sc. Chemistry 2010

University of South Carolina. Ph.D. Biological Sciences 2017 (anticipated)

Publications

Chukwurah E., Handy I., and Patel R.C. “ADAR1 and PACT contribute to efficient translation of transcripts containing HIV-1 trans-activating response (TAR) element” currently in review

Chukwurah E., and Patel R.C.“Phosphorylation of the RNA-induced silencing complex protein, TRBP, regulates PKR activity during cell stress” manuscript in preparation

International Presentations

Chukwurah E., and Patel RC. “Phosphorylation of the RNA-induced silencing complex protein, TRBP, regulates PKR activity during cell stress” December 3-7, 2016. ASCB 2016, San Francisco, CA. Poster.

Chukwurah E., and Patel RC. “Regulation of the interferon-induced eIf2α kinase PKR by TRBP phosphorylation” October 16-19, 2016. Cytokines 2016, San Francisco, CA. Poster.

Radetskyy R, Chukwurah E, Daher A, Burugu S, Routy J.P., Patel RC, Gatignol A. “A multiprotein complex with RNA binding proteins ADAR1, PACT, Tat and PKR contribute to low innate immunity against HIV-1” May 25 – 27 2016. ISHEID 2016, Marseille, FRA. Oral presentation.

Chukwurah E, Patel RC. “Regulation of Protein Kinase R (PKR) activation during cell stress by TRBP phosphorylation” April 2-6, 2016. ASBMB 2016, San Diego, CA.Poster.

Chukwurah E, Radetskyy R, Daher A, Gatignol A, Patel RC. “Inhibition of interferon (IFN)-induced Protein Kinase R (PKR) during HIV infection via altered function of PACT” October 11-14, 2015. Cytokines 2015, Bamberg, GER. Poster.

Daher A, Burugu S, Clerzius G, Shaw E, Chukwurah E, Radetskyy R, Labbé RP, Routy JP, Patel RC, Gatignol A. “PKR as a restriction factor during HIV-1 infection counteracted by virus-induced cellular mechanisms” July 19-22, 2015. IAS 2015, Vancouver, CAN. Poster.

Chukwurah E, Radetskyy R, Daher A, Gatignol A, Patel RC. “Mechanism of Protein Kinase R (PKR) Inhibition via altered function of PACT during HIV infection” May 18-23, 2015. CSHL Retroviruses, Cold Spring Harbor, NY. Poster.

Awards

  • Presidential Fellowship Recipient, University of South Carolina (August 2011- May 2015)
  • American Society for Biochemistry and Molecular Biology 2016 Graduate Student/ Postdoctoral Travel Award (April 2016)
  • American Society for Cell Biology 2016 Graduate Student Travel Award (September 2016)
  • University of South Carolina Graduate School Travel Grant (April 2016, December 2016)
  • University of South Carolina Biology Department Travel Award (May 2015, April 2016, and September 2016)
  • Cold Spring Harbor Laboratory Travel Award (May 2015)
  • SPARC Graduate Fellowship Recipient, University of South Carolina (May 2015 – May 2016)
  • International Student Merit Scholarship Recipient, Office of International Programs, University of South Carolina (January 2015)

Teaching

CHEM 102L Fundamental Chemistry II Laboratory Department of Chemistry and Biochemistry (Fall 2011- Spring 2012)

BIOL 302L Cellular & Molecular Biology Laboratory Department of Biological Sciences (Spring 2013 - present)