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

Transcriptional and chromatin regulation in interferon and innate antiviral gene expression. Au-Yeung N and Horvath CM. Cytokine & Growth Factor Reviews. 2018 December;44:11-17.

Sendai Virus Infection Induces Expression of Novel RNAs in Human Cells. Mandhana R and Horvath CM. Scientific Reports. 2018 November 14;8:16815.

Histone H2A.Z Suppression of Interferon-Stimulated Transcription and Antiviral Immunity Is Modulated by GCN5 and BRD2. Au-Yeung N and Horvath CM. iScience. 2018 August 31;6:68-82.

Constitutively Active MDA5 Proteins Are Inhibited by Paramyxovirus V Proteins. Mandhana R, Qian LK, and Horvath CM. Journal of Interferon & Cytokine Research. 2018 August;38(8):319-332.

RNA sensor LGP2 inhibits TRAF ubiquitin ligase to negatively regulate innate immune signaling. Parisien J-P, Lenoir JJ, Mandhana R, Rodriguez KR, Qian K, Bruns AM, and Horvath CM. EMBO reports. 2018 June 1;19(6):e45176.

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