Charles E. Samuel

Biography

Charles Samuel is the C. A. Storke II Professor. He earned a B.S. in Chemistry from Montana State and his Ph.D. in Biochemistry from U.C. Berkeley. He was a Damon Runyon Scholar at Duke Univ. Med. Sch. where he began work on interferon. At UCSB he served as Director of the Interdepartmental Biochemistry & Molecular Biology Program (BMSE) from 1987-95, as Founding Chair of the Department of Molecular, Cellular & Developmental Biology from 1995-98, and again as MCDB Chair from 2001-04. He is an NIH Research Career Development Awardee, an NIH MERIT awardee, a FASEB Wellcome Professorship awardee, a Humboldt Forschungspreis recipient, and an elected Fellow of the American Association for the Advancement of Science and the American Academy of Microbiology. He is an Associate Editor of the Journal of Biological Chemistry, and Journal of Interferon and Cytokine Research, and serves on the editorial board of Journal of Virology.

Research Description

The overall objective of the research in The Samuel Lab is to elucidate in molecular terms the mechanisms by which interferons exert their antiviral and cell growth control actions in mammalian cells. Present work includes biochemical and molecular genetic studies of two interferon-inducible enzymes, PKR and ADAR. PKR is a double-stranded RNA-dependent protein kinase induced by IFN, and activated by RNA-dependent autophosphorylation. PKR plays a major role in the regulation of translation of viral and cellular mRNAs and also modulates transcription and signaling. The ADAR1 deaminase is an RNA editing-enzyme that catalyzes the C-6 deamination of adenosine to yield inosine, thereby altering the genetic decoding and structure of RNAs. While PKR displays antiviral and proapoptic activities, ADAR1 is often proviral and antiapoptotic in virus-infected cells. Furthermore, PKR is not required for normal mouse embryogenesis, whereas ADAR1 is required.

Selected Publications

E BenDavid, C Yang, Y Zhou, CK Pfaller, CE Samuel, D Ma (2024) Host WD repeat-containing protein 5 inhibits protein kinase R-mediated integrated stress response during measles virus infection. Journal of Virology 98 (9), e01020-24

C E Samuel (2023) Interferon at the crossroads of SARS-CoV-2 infection and COVID-19 disease Journal of Biological Chemistry 299 (8)

DM Heithoff, SP Mahan, L Barnes, SA Leyn, CX George, …(2023) A broad-spectrum synthetic antibiotic that does not evoke bacterial resistance EBioMedicine 89

CE Samuel (2022) Interferonopathy resulting from dysregulation of interferon production. Journal of Interferon & Cytokine Research 42 (12), 655-657

E BenDavid, CK Pfaller, Y Pan, CE Samuel, D Ma (2022) Host 5′-3′ exoribonuclease XRN1 acts as a proviral factor for measles virus replication by downregulating the dsRNA-activated kinase PKR Journal of Virology 96 (22), e01319-22

DM Heithoff, L Barnes, SP Mahan, GN Fox, KE Arn, SJ Ettinger, ...(2022) Assessment of a smartphone-based loop-mediated isothermal amplification assay for detection of SARS-CoV-2 and influenza viruses JAMA Network Open 5 (1), e2145669-e2145669

CK Pfaller, CX George, CE Samuel (2021) Adenosine deaminases acting on RNA (ADARs) and viral infections Annual Review of Virology 8 (1), 239-264

Samuel, C.E. (2019) Adenosine deamnase acting on RNA1 (ADAR1), a suppressor of double-stranded RNA-triggered innate immune responses. J. Biol. Chem.: 294: 1710-1720.

Pataer, A., Ozpolat, B., Shao, R., Cashman, N.R., Plotkin, S.S., Samuel, C.E., et al. (2019) Therapeutic targeting of the PI4K2A/PKR lysosome network is critical for misfolded protein clearance and survival in cancer cells. Oncogene doi: 10.1038/s41388-019-1010-4.

Zhou, Y., Su, J.M., Samuel, C.E., and Ma, D. (2019) Measles virus forms inclusion bodies with properties of liquid organelles. J Virol. doi: 10.1128/JVI.00948-19

Bouxsein N.F, Leal, C., McAllister C.S., Li, Y., Ewert, K.K, Samuel, C.E. and Safinya, C.R. (2019). A 3D columnar phase of stacked short DNA organized by coherent membrane undulations. Langmuir 35(36):11891-11901.

Ma, D, George C.X., Nomburg, J., Pfaller, C.K., Cattaneo, R., and Samuel, C.E. (2018). Upon infection the cellular WD repeat-containing protein 5 localizes to cytoplasmic inclusion bodies and enhances measles virus replication. J. Virol.: doi: 10.1128/JVI.01726-17.

Tan,M.H., Li,Q., Shanmugam,R., Piskol,R., Kohler, J., et al. (2017) Dynamic landscape and regulation of RNA editing in mammals. Nature 550(7675):249-254.

George, C.X., Ramaswami, G., Li, J.B., Samuel, C.E. (2016) Editing of cellular self-RNAs by adenosine deaminase ADAR1 suppresses innate immune stress responses. J Biol Chem. 291:6158-68.

Kainulainen, M., Lau, S., Samuel, C.E., Hornung, V., Weber, F. (2016) NSs virulence factor of Rift Valley Fever Virus engages the F-box proteins FBXW11 and β-TRCP1 to degrade the antiviral protein kinase PKR. J Virol. 90:6140-6147.

George, C. X., Samuel, C. E. (2015) STAT2-dependent induction of RNA adenosine deaminse ADAR1 by type 1 interferon differs between mouse and human cells in the requirement for STAT1. Virology 485: 363-370.

Pfaller, C. K., Mastorakos, G.M., Matchett, W.E., Ma, X., et al. (2015) Measles virus defective interfering RNAs are generated frequently and early in the absence of C protein and can be destabilized by adenosine deaminase acting on RNA1-like hypermutations. J. Virol. 89: 7735-7747.

George, C.X., John, L., Samuel, C.E. (2014) An RNA Editor, Adenosine Deaminase Acting on Double-Stranded RNA (ADAR1). J. Interferon Cytokine Res. 34:437-46.

Pfaller, C.K., Radeke, M.J., Cattaneo, R., Samuel, C.E. (2014) Measles virus C protein impairs production of defective copyback double-stranded viral RNA and activation of protein kinase R. J. Virol. 88:456-68.

John, L., Samuel, C.E. (2014) Induction of stress granules by interferon and down-regulation by the cellular RNA adenosine deaminase ADAR1. Virology 454-455:299-310.