Investigators

Roberto Baccala, Ph.D.

Associate Professor
Autoimmunity & Viral Immunopathology
Department 858-434-1969

Research Focus

Our research focuses on mechanisms of immunopathology in autoimmune and anti-viral responses, with emphasis on three main areas. The first addresses the primary role of the innate immune system in systemic autoimmunity. Our earlier work in mouse models of lupus provided direct in vivo evidence for the essential role of type I interferons, endolysosomal Toll‐like receptors, and plasmacytoid dendritic cells in disease pathogenesis, thereby contributing to the current paradigm that abnormal activation of this innate immune pathway by self-nucleic acids is a key event in systemic autoimmunity. We also showed that the pathogenicity of this pathway can be controlled at the endolysosomal surface by modulating the function of SLC15A4, a peptide/histidine transporter and promising new therapeutic target. Current efforts aim at elucidating the mechanisms by which SLC15A4 promotes TLR responses and developing specific pharmacologic inhibitors. The second area of research investigates the contribution of microenvironmental triggers of innate immune activation in systemic autoimmunity. We found that certain viral and xenobiotic agents, particularly when acting in combination, can significantly increase the susceptibility to lupus‐like disease, including in otherwise non‐autoimmune mouse strains. These results support a multi-hit model of autoimmunity in which the effect of genetic predisposition is enhanced by microenvironmental exposures, and ongoing studies are examining the mechanistic basis for the observed synergisms. The third area of research addresses the role of the innate immune system in virus‐induced immunopathology using a novel mouse model of arenavirus‐induced lethality. We found that certain variants of the lymphocytic choriomeningitis virus cause in certain mouse strains severe vascular leakage, pulmonary edema, respiratory failure, and death, recapitulating key aspects of viral hemorrhagic fevers and other lethal viral diseases characterized by severe vascular injury, including COVID‐19. Notably, vascular leakage and disease severity correlated with the potency of the anti-viral immune response and the action of type I interferons on both immune and endothelial cells, providing a relevant in vivo model for mechanistic studies at the interface of the immune and the vascular systems.


Education

Ph.D. in Biology/Immunology, Pasteur Institute and University of Paris VII, 1989
B.S. in Biochemistry, ETH (Swiss Fed. Inst. Of Technology, Zurich, 1984


Professional Experience

2021 – Present, Current Associate Professor, San Diego BioMed
2008 – 2021 Associate Professor, The Scripps Research Institute
2000 – 2008 Assistant Professor, Department of Immunology, The Scripps Research Institute
1995 – 2000 Research Group Leader, Division of Hematology, C.H.U.V. Lausanne, Switzerland
1993 – 1995 Assistant Professor, Department of Immunology, Scripps Clinic & Research Foundation
1989 – 1993 Post-Doctoral Fellow, Department of Immunology, Scripps Clinic & Research Foundation


Honors and Awards

1993 New Investigator Award of the University of California
1993 Scholar Award of the American Foundation for AIDS Research
1989 – 1990 Postdoctoral Fellowship of the Swiss National Science Foundation
1987 – 1988 Fellowship of the French Government
1986 Fellowship of the Swiss National Science Foundation
1985 Fellowship of the Stefano Franscini Foundation, ETH Switzerland
1980 Fellowship of the Government of Canton Ticino, Switzerland

Select Publications

Baccala R, Gonzalez-Quintial R, Schreiber RD, Lawson BR, Kono DH, and Theofilopoulos AN 2012. Anti-IFN-alpha/beta Receptor Antibody Treatment Ameliorates Disease in Lupus-Predisposed Mice. J Immunol 189:5976-5984. PMID: 23175700.

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Santiago-Raber ML, Baccala R, Haraldsson KM, Choubey D, Stewart TA, Kono DH, and Theofilopoulos AN. 2003. Type-1 interferon receptor deficiency reduces lupus-like disease in NZB mice. J. Exp. Med. 197:777-788. PMID 12642605.

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Baccala R, Hoebe K, Kono DH, Beutler BA, and Theofilopoulos AN. 2007. TLR-dependent and TLR-independent pathways of type I interferon induction in systemic autoimmunity. Nat Med 13:543-551. PMID: 17479100.

Baccala R, Gonzalez-Quintial R, Blasius AL, Rimann I, Ozato K, Kono DH, Beutler B, and Theofilopoulos AN. 2013. Essential requirement for IRF8 and SLC15A4 implicates plasmacytoid dendritic cells in the pathogenesis of lupus. Proc Natl Acad Sci USA 110:2940-2945. PMID: 23382217.

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Gonzalez-Quintial R, Nguyen A, Kono DH, Oldstone MBA, Theofilopoulos AN, and Baccala R. 2018. Lupus acceleration by a MAVS-activating RNA virus requires endosomal TLR signaling and host genetic predisposition. PLoS ONE 13: e0203118. PMID: 30199535.

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Gonzalez-Quintial, R., Mayeux JM, Kono DH, Theofilopoulos AN, Pollard KM, and Baccala R. 2019. Silica exposure and chronic virus infection synergistically promote lupus-like systemic autoimmunity in mice with low genetic predisposition. Clin Immunol, 205:75-82. PMID: 31175964.

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Baccala, R., Welch, M.J, Gonzalez-Quintial, R., Walsh, K.B., Teijaro, J.R., Nguyen, A., Ng, C.T., Sullivan, B.M., Zarpellon, A., Ruggeri, Z.M., de la Torre, J.C., Theofilopoulos, A.N., and Oldstone, M.B.A. 2014. Type I interferon is a therapeutic target for virus-induced lethal vascular damage. Proc Natl Acad Sci USA, 111:8925-8930. PMID: 24889626.

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Theofilopoulos AN, Kono DH, Baccala R. The multiple pathways to autoimmunity. Nat Immunol. 2017 Jun 20;18(7):716-724. doi: 10.1038/ni.3731. PMID: 28632714; PMCID: PMC5791156.

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All of Dr. Roberto Baccala’s Publications