Curt M. Horvath Signal transduction & gene regulation in innate immune responses to cancer and viruses

Research Interests

How do polypeptide signals, including an array of cytokines important for innate and adaptive immune responses, specify alterations in gene expression patterns in the nucleus?  Greater knowledge of these processes will lead to improved diagnostic tools and treatment options for many diseases resulting from defective cell signaling like cancer, immune deficiencies, chronic inflammation, and birth defects.  Several biomedically relevant signaling pathways are under investigation, examining both the activation and propagation of intracellular signaling and the general and gene-specific phenomena controlling downstream transcriptional regulation.

We are particularly interested in the interactions between the innate immune system and viral pathogens in human cells, and one system that we have widely explored is cell-intrinsic innate antiviral immunity.  Infection by RNA viruses results in cytosolic accumulation of chemically distinct, non-self RNA species.  Sentry proteins in the cytoplasm recognize these non-self RNAs, and trigger downstream signal transduction events that culminate in activated antiviral transcription.  Induced transcription factors IRF3 and NFκB accumulate in the nucleus where they drive the expression of virus-induced genes, including the primary antiviral cytokine, IFNβ.  IFNβ binds to receptors to activate the JAK-STAT-ISGF3 signaling system to activate the expression of diverse direct and indirect antiviral effectors.  Our research in cytokine signaling mechanisms has resulted in many new and exciting research directions for future study in the areas of immune regulation, gene regulation, cancer biology, host-pathogen interactions, virology, and cell biology.

Selected Publications

The Human STAT2 Coiled-Coil Domain Contains a Degron for Zika Virus Interferon Evasion. Parisien J-P, Lenoir JJ, Alvarado G, and Horvath CM. Journal of Virology. 2022 January;96(1):e0130121.

Immune regulator LGP2 targets Ubc13/UBE2N to mediate widespread interference with K63 polyubiquitination and NF-κB activation. Lenoir JJ, Parisien J-P, and Horvath CM. Cell Reports. 2021 December 28;37(13):110175.  

Circuits between infected macrophages and T cells in SARS-CoV-2 pneumonia. Grant RA, Morales-Nebreda L, Markov NS, Swaminathan S, Querrey M, Guzman ER, Abbott DA, Donnelly HK, Donayre A, Goldberg IA, Klug ZM, Borkowski N, Lu Z, Kihshen H, Politanska Y, Sichizya L, Kang M, Shilatifard A, Qi C, Lomasney JW, Argento AC, Kruser JM, Malsin ES, Pickens CO, Smith SB, Walter JM, Pawlowski AE, Schneider D, Nannapaneni P, Abdala-Valencia H, Bharat A, Gottardi CJ, Budinger GRS, Misharin AV, Singer BD, Wunderink RG and The NU SCRIPT Study Investigators (Horvath CM). Nature. 2021 February 25;590(7847):635-641.  

RNA Helicase LGP2 Negatively Regulates RIG-I Signaling by Preventing TRIM25-Mediated Caspase Activation and Recruitment Domain Ubiquitination. Quicke KM, Kim KY, Horvath CM, and Suthar MS. Journal of Interferon & Cytokine Research. 2019 November;39(11):669-683.   

IFN-γ–inducible antiviral responses require ULK1-mediated activation of MLK3 and ERK5. Saleiro D, Blyth GT, Kosciuczuk EM, Ozark PA, Majchrzak-Kita B, Arslan AD, Fischietti M, Reddy NK, Horvath CM, Davis RJ, Fish EN, and Platanias LC. Science Signaling. 2018 November 20;11(557):eaap9921.  

View all publications by Curt M. Horvath listed in the National Library of Medicine (PubMed). Current and former IBiS students in blue.