Department of Microbiology & Immunology
MRB Route 1019
Phone: (409) 772-4917
|PhD | 2009 | MRC National Institute for Medical Research, London, England|
|MSc | 1999 | Weizmann Institute of Science, Rehovot, Israel|
|BSc | 1996 | Universidad Nacional Autonoma de Mexico, Mexico|
Overview: Innate immunity to virus infection. Pattern recognition receptor signaling, ubiquitin and E3‐ ubiquitin ligases in regulation of virus replication. Antagonism of innate immune response by viruses.
Work in the Rajsbaum laboratory focuses on the study of host‐pathogen interactions and innate immune responses to viruses. Innate and cell‐intrinsic immune responses are essential to protect host cells against pathogens. Members of the tripartite motif (TRIM) family of E3‐ubiquitin ligases are involved in antiviral immunity by directly inhibiting viral replication or by sensing and transmitting signals to induce antiviral cytokines. However, to establish productive infection, viruses have developed sophisticated mechanisms to counteract host immune responses, including targeting TRIM proteins. Our lab is interested in elucidating the mechanisms by which TRIM proteins and other signaling molecules regulate antiviral functions and how viruses (Influenza, dengue, Zika, West Nile, Ebola, Nipah and other viruses) evade these immune responses. We and others have shown that members of the TRIM family (TRIM5, TRIM6, TRIM25) catalyze the synthesis of unanchored polyubiquitin chains that activate antiviral signaling pathways. In addition, new evidence indicates that TRIMs and ubiquitination of viral proteins can have both antiviral and proviral functions depending on the host environment. Our lab aims to dissect these molecular mechanisms that regulate virus replication using in vitro biochemical methods, primary immune cells, and in vivo animal models. We also hope to identify new components of innate immune signaling pathways and viral factors that could be targeted for therapeutic intervention.
1: Rajsbaum R*, Versteeg GA*, Schmid S, Maestre AM, Belicha-Villanueva A,
Martinez-Romero C, Patel JR, Morrison J, Pisanelli G, Miorin L, Laurent-Rolle M,
Moulton HM, Stein DA, Fernandez-Sesma A, tenOever BR, Garcia-Sastre A. Unanchored K48-linked polyubiquitin synthesized by the E3-ubiquitin ligase TRIM6 stimulates the interferon-IKKε kinase-mediated antiviral response. Immunity. 2014 Jun 19;40(6):880-95.
2: Rajsbaum R, Garcia-Sastre A, Versteeg GA. TRIMmunity: the roles of the TRIM E3-ubiquitin ligase family in innate antiviral immunity. J Mol Biol. 2014 Mar 20;426(6):1265-84. Review.
3: Rajsbaum R, Garcia-Sastre A. Viral evasion mechanisms of early antiviral responses involving regulation of ubiquitin pathways. Trends Microbiol. 2013 Aug;21(8):421-9. Review.
4: Versteeg GA*, Rajsbaum R*, Sanchez-Aparicio MT, Maestre AM, Valdiviezo J, Shi M, Inn KS, Fernandez-Sesma A, Jung J, Garcia-Sastre A. The E3-ligase TRIM family of proteins regulates signaling pathways triggered by innate immune pattern-recognition receptors. Immunity. 2013 Feb 21;38(2):384-98.
5: Rajsbaum R, Albrecht RA, Wang MK, Maharaj NP, Versteeg GA, Nistal-Villan E, Garcia-Sastre A, Gack MU. Species-specific inhibition of RIG-I ubiquitination and IFN induction by the influenza A virus NS1 protein. PLoS Pathog. 2012;8(11):e1003059
6: Rajsbaum R, Stoye JP, O'Garra A. Type I interferon-dependent and –independent expression of tripartite motif proteins in immune cells. Eur J Immunol. 2008 Mar;38(3):619-30.