Research Focus
Honors
Selected Publications
Contact
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Korennykh?Group Website

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Research Focus
We aim to understand mechanisms of human innate immunity, response to damage, and stress. In particular, we are interested in structural and cell biology of pathways mediated bydsRNA, other kinds of RNA, and by receptor proteins that recognize or process these RNA molecules.

Intracellular response todsRNA

Double-stranded RNA ordsRNAis a major regulator of gene expression in all mammalian cells. A number of membrane-tethered,cytosolicand nuclear proteins serve as receptors that recognizedsRNAand controldsRNAresponse. Often,dsRNAresponse is linked to the production ofinterferons, pro-inflammatory cytokines and control of innate and adaptive immunity.
Broader roles of these programs in homeostasis, cell cycle, differentiation, senescence and aging are also emerging.

Other signaling RNA

One of the key programs activated bydsRNAin all mammalian cells involves cleavage of the intracellular RNA pool by akinasefamily receptor,RNaseL. We are interested in structural and cell biology ofRNaseL.
We are also interested in a sister protein ofRNaseL,Ire1.Ire1controls the unfolded protein response (UPR) by splicing anintronfrom a transcription factorXBP1mRNA-- without using thespliceosome. As we have shown recently,Ire1andRNaseL employ similar mechanisms for RNA recognition.

Our methods

X-ray crystallography
?Human/murinecell biology?
Biochemistry?
Biophysics?
Systems biology
Some of our recent work includes studies of receptors (sensors) involved in stress and immune responses.


Research Areas
Chemical Biology



Honors
Burroughs Wellcome Fund Award (2014)
Sidney Kimmel Foundation Award (2014)
General Biology Research Award, 6th Annual Awards, BioMed Central (London, 2011)
UCSF Dean’s Postdoctoral Research Prize and Lecture (2010)
Jane Coffin Childs Postdoctoral Fellow (2007-2010)
Cancer Research Institute (CRI) Postdoctoral Fellowship (2007)
Burroughs Wellcome Graduate Fellow (2001-2003)
George Soros International Scholar (ISSEP, 1995)


Selected Recent Publications
Han, Y.; Donovan, J.;Rath, S.; Whitney, G.;Chitrakar, A.;Korennykh, A., "Structure of HumanRNaseL Reveals the Basis for Regulated RNA Decay in the IFN Response."Science2014,343(6176), 1244-1248.
Donovan, J.;Dufner, M.;Korennykh, A., "Structural basis forcytosolicdouble-stranded RNA surveillance by humanoligoadenylatesynthetase."Proceedings of the National Academy of Sciences of the United States of America2013,110(5), 1652-1657.
Han, Y.; Whitney, G.; Donovan, J.;Korennykh, A., "Innate Immune Messenger2-5ATethers HumanRNaseLintoActive High-Order Complexes."Cell Reports2012,2(4), 902-913.
Korennykh, A.; Walter, P., "Structural Basis of the Unfolded Protein Response."Annual Review of Cell and Developmental Biology, Vol 282012,28, 251-277.
Korennykh, A. V.;Korostelev, A. A.;Egea, P. F.; Finer-Moore, J.; Stroud, R. M.; Zhang, C.;Shokat, K. M.; Walter, P., "Structural and functional basis for RNA cleavage byIre1."Bmc Biology2011,9.
Korennykh, A. V.;Egea, P. F.;Korostelev, A. A.; Finer-Moore, J.; Stroud, R. M.; Zhang, C.;Shokat, K. M.; Walter, P., "Cofactor-mediated conformational control in thebifunctionalkinase/RNaseIre1."Bmc Biology2011,9.
Plantinga, M. J.;Korennykh, A. V.;Piccirilli, J. A.;Correll, C. C., "TheRibotoxinRestrictocinRecognizes Its RNA Substrate by Selective Engagement of Active Site Residues."Biochemistry2011,50(14), 3004-3013.
Rubio, C.;Pincus, D.;Korennykh, A.;Schuck, S.;El-Samad, H.; Walter, P., "Homeostatic adaptation to endoplasmic reticulum stress depends onIre1kinaseactivity."Journal of Cell Biology2011,193(1), 171-184.
Aragon, T.; van Anken, E.; Pincus, D.; Serafimova, I. M.; Korennykh, A. V.; Rubio, C. A.; Walter, P., "Messenger RNA targeting to endoplasmic reticulum stress signalling sites."Nature 2009, 457 (7230), 736-U9.
Korennykh, A. V.;Egea, P. F.;Korostelev, A. A.; Finer-Moore, J.; Zhang, C.;Shokat, K. M.; Stroud, R. M.; Walter, P., "The unfolded protein response signals through high-order assembly of Ire1."Nature2009,457(7230),687-U2.
Plantinga, M. J.;Korennykh, A. V.;Piccirilli, J. A.;Correll, C. C., "Electrostatic interactions guide the active site face of a structure-specific.ribonucleaseto its RNA substrate."Biochemistry2008,47(34), 8912-8918.
Korennykh, A. V.; Correll, C. C.; Piccirilli, J. A., "Evidence for the importance of electrostatics in the function of two distinct families of ribosome inactivating toxins."Rna-a Publication of the Rna Society 2007, 13 (9), 1391-1396.
Korennykh, A. V.; Plantinga, M. J.; Correll, C. C.; Piccirilli, J. A., "Linkage between substrate recognition and catalysis during cleavage of sarcin/ricin loop RNA by restrictocin."Biochemistry 2007, 46 (44), 12744-12756.
Korennykh, A. V.;Piccirilli, J. A.;Correll, C. C., "The electrostatic character of the ribosomal surface enables extraordinarily rapid target location by ribotoxins."Nature Structural & Molecular Biology2006,13(5), 436-443.