Curt M. Horvath Professor of Molecular Biosciences

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

LGP2 synergy with MDA5 in RLR-mediated RNA recognition and antiviral signalingBruns AM and Horvath CM. Cytokine. 2015 August;74(2):198-206.

The Innate Immune Sensor LGP2 Activates Antiviral Signaling by Regulating MDA5-RNA Interaction and Filament AssemblyBruns AM, Leser GP, Lamb RA, and Horvath CM. Molecular Cell. 2014 September 4;55(5):771-781.

High-Density Nucleosome Occupancy Map of Human Chromosome 9p21–22 Reveals Chromatin Organization of the Type I Interferon Gene ClusterFreaney JE, Zhang Q, Yigit E, Kim R, Widom J, Wang J-P, and Horvath CM. Journal of Interferon & Cytokine Research. 2014 September 2;34(9):676-685.

MDA5 and LGP2: Accomplices and Antagonists of Antiviral Signal TransductionRodriguez KR, Bruns AM, and Horvath CM. Journal of Virology. 2014 August;88(15):8194-8200.

Extensive Cooperation of Immune Master Regulators IRF3 and NFκB in RNA Pol II Recruitment and Pause Release in Human Innate Antiviral TranscriptionFreaney JE, Kim R, Mandhana R, and Horvath CM. Cell Reports. 2013 September 12;4(5):959-973.

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