Faculty
Curt M. Horvath, PhD
Professor
BMBCB/ENHRI
PhD, Northwestern University
Email: horvath@northwestern.edu
Phone: (847) 491-5530
Fax: (847) 491-4400
Room: Pancoe Rm 4401
Research Interests
Signal transduction and gene regulation in innate immune responses to cancer and viruses
My laboratory studies how polypeptide signals, cytokines important for antiviral and antitumor immunity, specify alterations in gene expression patterns. 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 dysfunction, and birth defects. We are particularly interested in the interactions between the antiviral immune system and viral pathogens.
The regulation of inducible transcriptional responses is being studied by focusing on transcription activating proteins involved in Interferon signaling called STATs (for Signal Transducers and Activators of Transcription) and IRFs (for Interferon Regulatory Factors). STATs become active as DNA-binding factors in response to cell surface receptor activation by the polypeptides and directly bind to the promoters of target genes. IRFs are constitutive DNA binding proteins with regulated subcellular distribution. Both families of proteins activate gene expression alone and in combination with other cellular proteins to give rise to a wide range of biological responses involved in innate and adaptive immune function.
Two major questions currently dominate the research in the lab. The first question is "How do STAT and IRF proteins function as transcription factors?" We have found several transcriptional co-activators that crucial for IFN responses and continue to investigate their role in gene regulation and chromatin remodeling. The second question is " How do viruses recognize and avoid IFN responses and STAT protein functions?". We have discovered a diverse range of STAT-directed IFN evasion mechanisms in the paramyxovirus family of RNA viruses, ranging from virus-induced ubiquitylation and degradation to cytoplasmic sequestration. The pursuit of both questions has resulted in many new and exciting research directions for future study in the areas of immune regulation, gene regulation, host-pathogen interactions, virology, and cell biology.
Selected Publications
Regulating Immune Response Using Polyvalent Nucleic Acid-Gold Nanoparticle Conjugates. Massich MD, Giljohann DA, Seferos DS, Ludlow LE, Horvath CM, Mirkin CA. Mol Pharm. 2009 Oct 7. [Epub ahead of print]
Paramyxovirus disruption of interferon signal transduction: STATus report. Ramachandran A, Horvath CM. J Interferon Cytokine Res. 2009 Sep;29(9):531-7.
A shared interface mediates paramyxovirus interference with antiviral RNA helicases MDA5 and LGP2. Parisien JP, Bamming D, Komuro A, Ramachandran A, Rodriguez JJ, Barber G, Wojahn RD, Horvath CM. J Virol. 2009 Jul;83(14):7252-60. Epub 2009 Apr 29.
A point mutation, E95D, in the mumps virus V protein disengages STAT3 targeting from STAT1 targeting. Puri M, Lemon K, Duprex WP, Rima BK, Horvath CM. J Virol. 2009 Jul;83(13):6347-56. Epub 2009 Apr 22.
Regulation of signal transduction by enzymatically inactive antiviral RNA helicase proteins MDA5, RIG-I, and LGP2. Bamming D, Horvath CM. J Biol Chem. 2009 Apr 10;284(15):9700-12. Epub 2009 Feb 11.
STAT2 is a primary target for measles virus V protein-mediated alpha/beta interferon signaling inhibition. Ramachandran A, Parisien JP, Horvath CM. J Virol. 2008 Sep;82(17):8330-8. Epub 2008 Jun 25.
Henipavirus V protein association with Polo-like kinase reveals functional overlap with STAT1 binding and interferon evasion. Ludlow LE, Lo MK, Rodriguez JJ, Rota PA, Horvath CM. J Virol. 2008 Jul;82(13):6259-71. Epub 2008 Apr 16.
Enabled interferon signaling evasion in an immune-competent transgenic mouse model of parainfluenza virus 5 infection. Kraus TA, Garza L, Horvath CM. Virology. 2008 Feb 5;371(1):196-205. Epub 2007 Oct 26.
View all publications by Curt M. Horvath listed in the National Library of Medicine (PubMed). IBiS students in blue