Basta | Biomedical and Molecular Sciences | School of Medicine

Sam Basta PhD

Position(s)

Professor

Contact Info

613-533-6000 x36648

Faculty Bio

BSc, Biochemistry. Scotland, UK.

MSc, Immunology. England, UK.

PhD, Viral Immunology. Switzerland.

Post-Doctoral Fellow ( Viral Immunology section) NIH, USA.

Post-Doctoral Scientist (Immunology Program), University of Constance, Germany.

Research Interests

Antigen presentation of viral and tumour epitopes via MHC class-I to cytotoxic CD8+ T cells.
Immunobiology of antigen presenting cells e.g Mø, DCs.
Tumour immunology, immunotherapy.

For 4th Year Project Applicants

Interest applicants must have enrolled for MICR 386 as well as apply for the total 12 units projects (either MICR 499 or equivalent / or HSCI 598 + 599)

Research Topics

Anti-viral CD8+ T cell responses: Employing the well-characterized LCMV model of infection, we discovered that changes in the viral load, significantly altered T cell hierarchies (Microbes Infect. 2010). We also reported on the role of cross-presentation in shaping immunodominance in T cells after virus infection (Viral Immunology 2007) and highlighted a role for TLR ligands in regulating antiviral CD8+ T cell responses (J. Virol. 2011, J. Leukoc. Biol. 2011, JGV. 2021).

Cross-priming and cross-presentation: We studied and defined important molecular and cellular requirements needed for the activation of CD8+ T cells via cross priming (Science 2004, J. Immunol. 2002) and illustrated that the outcome of cross-priming during virus infection is not directly linked to the ability of the antigen to be cross-presented (Eur. J. Immunol. 2010).

Spleen-derived macrophages (Sp-Mø): We reported on how Sp-Mø cross-present viral antigens (J. Immunol. Meth 2008 & Immunol & Cell Biology 2010 - Outstanding Observation). We also characterizzed their ability to polarize into (M1) or alternatively activated (M2) Mø (Immunobiology 2014). Furthermore, we reported on how M2a polarized Mø can stimulate epitope-specific CD8+ T cells via antigen presentation to produce IFN-γ (Front Immunol.2017). Moreover, that Sustained IL-4 priming of Mø enhances the inflammatory response to TLR7/8 ligands (J. Leukoc. Biol. 2022).

Host-virus interactions: We studied CD8+ T cells activation in various viral models of infection e.g., influenza, LCMV and, vaccinia virus (Nat.Med. 2001, Viral Immunology 2003, Science 2004, J. Immunol. 2002, 2005). Our collaboration with Dr. Ohashi (Cell 2011) utilized the LCMV model to reveal an important role for IL-7 as a therapeutic model to alter the outcome of chronic viral infection.

Cytokine immune regulation and cytokine tumour immunotherapy:

In collaboration with Dr. Gee, we demonstrated the following:

IL-27 Improves Prophylactic Protection Provided by a Dead Tumor Cell Vaccine in a Mouse Melanoma Model. (Frontiers in Immunology, 2022).
Differential TLR7-mediated cytokine expression by R848 in M1vs M2 Mø after LCMV infection. (Journal of General Virology. 2021)
Initial virus infection blocks production of bacterial-induced IL-12/23 expression (Che Mat et al, 2018, Cytokine).

Selected Publications:

*Petrina M, *Alothaimeen T, Bouzeineddine NZ, Trus E, Banete A, Gee K#, and Basta S#. Granulocyte Macrophage Colony Stimulating Factor exerts dominant effects over Macrophage Colony Stimulating Factor during Macrophage differentiation. Inflammation Research. 2023. In press. #Corresponding author. *Contributed equally.
Seaver K, Kourko O, Gee K, Greer PA, and Basta S#. IL-27 Improves Prophylactic Protection Provided by a Dead Tumor Cell Vaccine in a Mouse Melanoma Model. Frontiers in Immunology. 2022
Banete A, Barilo J, Whittaker R and Basta S#. The Activated Macrophage - A Tough Fortress for Virus Invasion: How Viruses Strike Back. Frontiers in Microbiology. 2022.
Alothaimeen T, Trus E, Basta S#, and Gee K#. Differential TLR7-mediated cytokine expression by R848 in M-CSF versus GM-CSF-derived macrophages after LCMV infection. Journal of General Virology. 2021.
Banete A, Gee K and Basta S#. Sustained IL-4 priming of macrophages enhances the inflammatory response to TLR7/8 ligand R848. Journal of Leukocyte Biology 2022.
Petrina M, Martin J, and Basta S#. Granulocyte macrophage colony-stimulating factor has come of age: from a vaccine adjuvant to antiviral immunotherapy. Cytokine and Growth Factor Reviews. 2021,
Alothaimeen T, Seaver K, Mulder R, Gee K#, and Basta S#. GM-CSF-derived macrophages exhibit distinctive early immune response to lymphocytic choriomeningitis virus infection. 2020 Viral Immunology.
Che Mat, N*, Siddiqui S*, Mehta D, Seaver K, Banete A, Alothaimeen T, Gee K#, and Basta S#. Lymphocytic Choriomeningitis Virus Infection of Dendritic Cells interferes with TLR-induced IL-12/IL-23 Expression. Cytokine. 2018. 108:105-114.
Banete A, Seaver K, Bakshi D, Gee K and *Basta S. On taking the STING out of immune activation. Journal of Leukocyte Biology. 2018.
Mulder R, Banete A, Seaver K, and *Basta S. M(IL-4) tissue macrophages support efficient interferon-gamma production in antigen-specific CD8+ T cells with reduced proliferative capacity. Frontiers in Immunology. 2017
The Role of Virus Infection in Deregulating the Cytokine Response to Secondary Bacterial Infection. Mehta D, Petes C, Gee K and *Basta S. *Corresponding author. J Interferon Cytokine Res. 2015.
Mulder R, Banete A and *Basta S. Spleen-derived macrophages are readily polarized into classically activated (M1) or alternatively activated (M2) states. *Corresponding author. Immunobiology. 2014.
Siddiqui S and *Basta S. CD8+ T Cell Immunodominance to Lymphocytic Choriomeningitis Virus is Modified in the Presence of Toll-Like Receptor Agonists. J Virol. 2011.
Gambhir V, Kim J, Siddiqui S, Jones G and *Basta S. Influence of 1,25(OH)2D3 on TLR-induced activation of antigen presenting cells is dependent on the order of receptor engagement. Immunobiology. 2011
Siddiqui S, Alatery A, Kus A, *Basta S. TLR engagement prior to virus infection influences MHC-I antigen presentation in an epitope-dependent manner as a result of nitric oxide release. *Corresponding author. J. Leukoc. Biol. 2011.
Mulder DJ, Pooni A, Mak N, David J. Hurlbut DJ, Basta S, and Justinich C. The role of antigen presentation by esophageal epithelial cells in eosinophilic esophagitis. American Journal of Pathology. 2011. 178:744-53.
Pellegrini M, Calzascia T, Elford A, Shahinian A, Lang P, Morre M, Tedder T, Sparwasser T, Nussenzweig M, Basta S., Ohashi P and Mak T. IL-7 engages multiple mechanisms to overcome chronic viral infection and limit organ pathology. Cell. 18:601-13 2011.
Alatery A, Tarrab E, Lamarre A, and *Basta, S. The outcome of cross-priming during virus infection is not directly linked to the ability of the antigen to be cross-presented. Eur. J Immunol. 2010. 40(8):2190-9. 2010. *Corresponding author. (Funded by NSERC).
Alatery A, Siddiqui S, Chan M, Kus A, Petrof E, and *Basta, S. Cross but not direct presentation of cell-associated virus antigens by spleen macrophages is influenced by their differentiation state. Immunol & Cell Biology. 2010. 88:3-12. *Corresponding author. (Funded by NSERC).
Siddiqui, S, Tarrab E, Lamarre A, and *Basta, S. Altered Immunodominance hierarchies of CD8+ T cells in the spleen after infection at different sites is contingent on high virus inoculum. Microbes & Infection. 2010. 12:324-30. *Corresponding author. (Funded by NSERC).
Alatery A and *Basta S. An efficient culture method for generating large quantities of mature mouse splenic macrophages. J. Immunol. Methods. 2008. 338:47-57 (Funded by NSERC). *Corresponding author.
Schlosser E, Fischer S, Basta S, Busch D, Gander B, and Groettrup M. Coencapsulation of adjuvants and antigen into the same biodegradable microspheres enables the generation of potent cytotoxic T lymphocyte responses. Vaccine. 2008. 26:1626-37.
Dunbar E, Alatery A and *Basta S. Cross-priming of a single viral protein from lymphocytic choriomeningitis virus alters immunodominance hierarchies of CD8+ T cells during subsequent viral infections. Viral Immunology. 2007. 20:585-98. (Funded by NSERC). *Corresponding author.
Basta S, Stoessel R, Basler M, van den Broek M, and Groettrup M. Cross-Presentation of the Long-Lived Lymphocytic Choriomeningitis Virus Nucleoprotein Does Not Require Neosynthesis and Is Enhanced via Heat Shock Proteins. J. Immunol. 2005.
Chen W, Pang K, Masterman K, Kennedy G, Basta S, Dimopoulos N, Hornung F, Smyth M, Bennink JR, and Yewdell. JW. Reversal in the Immunodominance Hierarchy in Secondary CD8+ T Cell Responses to Influenza A Virus: Roles for Cross-Presentation and Lysis-Independent Immunodomination. J. Immunol. 2004. 173:5021-5027. (NIH, USA).
*Norbury CC, *Basta S, Donohue KB, Tscharke DC, Princiotta MF, Berglund P, Gibbs J, Bennink JR, & Yewdell JW. CD8+ T cell cross-priming via transfer of proteasome substrates. Science. 2004. 304:1318-21. *Primary authorship. (NIH, USA).
Chen W, Masterman K, Basta S, Haeryfar SM, Dimopoulos N, Knowles B, Bennink JR and Yewdell JW. Cross-priming of CD8+ T cells by viral and tumor antigens is a robust phenomenon. Eur. J. Immunol. 2004. 34:194–199. (NIH, USA).
Cho Y, Basta S, Chen W, Bennink JR, Yewdell JW. Heat-Aggregated Noninfectious Influenza Virus Induces a More Balanced CD8(+)-T-Lymphocyte Immunodominance Hierarchy Than Infectious Virus. J. Virol. 2003. 77:4679-84. (NIH, USA).
Basta S, Chen W, Bennink JR, Yewdell JW. Inhibitory effects of cytomegalovirus proteins US2 and US11 point to contributions from direct priming and cross-priming in induction of vaccinia virus-specific CD8(+) T cells. J Immunol. 2002. 168:5403-8. (NIH, USA).
Chen W, Calvo PA, Malide D, Gibbs J, Schubert U, Bacik I, Basta S, O'Neill R, Schickli J, Palese P, Henklein P, Bennink JR, Yewdell JW. A novel influenza A virus mitochondrial protein that induces cell death. Nat. Med. 2001. 7:1306-12. (NIH, USA).

Team

Faculty Bio

Research Interests

For 4th Year Project Applicants

Research Topics

Selected Publications:

Faculty