Our laboratory focuses on understanding the mechanisms that regulate the directed migration of immune cells into tissue compartments during viral infection. Thus, the interactions between cytokines and chemotactic proteins or chemokines are being evaluated. We have identified novel chemokine-dependent mechanisms for innate and adaptive immune cell trafficking to the liver. Additionally, antiviral events mediated by chemokines are being evaluated. These studies will yield significant novel information for developing antiviral and anticancer treatment protocols.

Biography

Thais P. Salazar-Mather, Assistant Professor of Medical Science in the Department of Molecular Microbiology and Immunology, focuses her research on understanding the interaction of pathogens with the host immune system. She has developed a unique expertise in mechanisms controlling cellular trafficking for defense against infections in tissues. Dr. Salazar-Mather's goals are aimed at defining the molecular events controlled by cytokines and chemokines for the delivery of immune cell functions to different anatomical sites and evaluating antiviral events mediated by chemokines. She serves as an Ad Hoc reviewer for several journals in her field and is a member of NIH Study Sections. Dr. Salazar-Mather has received the Dean's Teaching in Excellence Award in 2005, 2006, 2007, 2008, and 2009 in recognition of exemplary teaching in Medical Microbiology.

Research Description

Our laboratory is focused on understanding how immune cells work in concert to eliminate pathogens from infected tissue sites. Central to this process are a group of soluble proteins called cytokines that are produced by immune cells in order to communicate and coordinate the appropriate offensive response. Chemotactic cytokines or chemokines act to direct the movement or trafficking of immune cells to tissues during infection or inflammation. Research in my laboratory is characterizing the interplay between cytokines and chemokines, and their precise and nonredundant roles in regulation of innate and adaptive immune cell trafficking. These mechanisms are being dissected in the in vivo context of a virus infection. We have identified novel chemokine-dependent mechanisms promoting immune cell trafficking to the liver during infection. Recent efforts have identified a role for type 1 interferons in the regulation of chemokine responses that mobilize the egress of monocyte/macrophages from the bone marrow to peripheral tissues. Current studies are aimed at defining the intracellular signaling pathways that lead to chemokine induction in the bone marrow, and the mechanisms that promote entry of innate immune cells into infected tissue sites. Many basic techniques in cellular immunology, virology, molecular biology, histology and in vivo trafficking assays are being used to further understand inflammatory and protective responses in various tissues. Information resulting from these studies continues to enhance our understanding of in vivo chemokine biology and function, as well as yield significant novel information for developing antiviral and anticancer treatment protocols.

Awards

ACADEMIC HONORS
Recipient of Dean's Teaching Excellence Award for Medical Microbiology, 2005, 2006, 2007, 2008, 2009

Affiliations

PROFESSIONAL AFFILIATIONS
Member of American Association of Immunologists
Member of Society for Natural Immunity
Member of American Society for Microbiology
Member of American Society for Virology

Funded Research

RESEARCH GRANTS
Active

• NIH(NCI) R01-CA102708; Key Innate Mechanisms of Natural Killer Cell Trafficking; September 1, 2003-June 30, 2009; Principal Investigator; Direct Costs - $875,000/5yr; 50% effort


• NIH R01-A146709; NK Receptors and CD1 Roles in NK and NKT Cell Function; April 1, 2001-March 31, 2006; Co-Principal Investigator; $750,000/5yr; 10% effort

• NIH 1P20-RR015578 (COBRE); Program, "Center for Genetics and Genomics" (John Sedivy-PI); Project A, "Characterization of Events Regulating the Balance Between Resistance and Infection"; October 1, 2002-August 31, 2005; Co-Principal Investigator (Christine Biron-Project PI); 10% effort


• NIH KO1-CA79076; Natural Killer Cell Trafficking and Delivery of Function; September 1, 1998-August 31, 2003; Principal Investigator; Direct Costs - $581,562/5yr; 80% effort


• NIH Research Supplement Grant (to CA41268); Natural Killer Cell Growth and Development; July 1, 1996-August 31, 1998; Direct Costs - $99,519/2.6yr; 100% effort

Teaching Experience

Integrated Medical Microbiology/Infectious Diseases; primary lecturer in Immunology, Virology and Bacteriology to first year medical students; and Microbial Pathogenesis.

Courses Taught

• Graduate Independent Study (BI0293)
• Independent Research (BIO195/195)
• Medical Microbiology (BI158)
• Microbial Pathogenesis (BI0264 (Staff))
• Scientific Foundations of Medicine/Microbiology (BI365S03 (Co-Course Leader))

Selected Publications

• Crane, M.J., K.L Hokeness-Antonelli, and T.P. Salazar-Mather. Regulation of inflammatory monocyte/macrophage recruitment from the bone marrow during murine cytomegalovirus infection: role for type I interferons in localized induction of CCR2 ligands. J. Immunol. 183: 2810-2817. 2009.(2009)
• Wesche-Soldato,D.E., C. Chun-Shiang, S.H. Gregory, T.P. Salazar-Mather, C.A. Ayala, and A. Ayala. CD8+ T cells promote inflammation and apoptosis in the liver after sepsis: role of Fas-FasL. Am. J. Pathol., 171:87-96, 2007(2007)
• Hokeness, K.L., E.S. Deweerd, M.W. Munks, C.A. Lewis, R.P. Gladue, and T.P. Salazar-Mather. CXCR3-dependent recruitment of antigen-specific T lymphocytes to liver during murine cytomegalovirus infection. J Virol. 81:1241-1250, 2007.(2007)
• Hokeness-Antonelli, K.L., M. J. Crane, A.M. Dragoi, W-M. Chu, and T.P Salazar-Mather. IFN-α/β-mediated inflammatory responses and antiviral defense in liver are TLR9-independent but MyD88-dependent during murine cytomegalovirus infection. J. Immunol. 179:6176-6183. 2007.(2007)
• Salazar-Mather, T.P. and K.L Hokeness. Cytokine and chemokine networks: Pathways to antiviral defense. Curr. Top. Micro. Immunol. 303:29-46, 2006.(2006)
• Huang D, F.D. Shi, S. Jung, G.C. Pien, J. Wang J, T.P. Salazar-Mather, T.T. He J.T. Weaver, H.G. Ljunggren, C.A. Biron, D.R. Littman, R.M. Ransohoff. The neuronal chemokine CX3CL1/fractalkine selectively recruits NK cells that modify experimental autoimmune encephalomyelitis within the central nervous system. FASEB J. 7:896-905, 2006.(2006)
• Hokeness, K.L., W.A. Kuziel, C.A. Biron, and T.P. Salazar-Mather. Monocyte chemoattactant protein-1 and CCR2 interactions are required for IFN-α/β-induced inflammatory responses and antiviral defense in liver. J. Immunol. 174:1549-1556, 2005.(2005)
• Serbina, N., T.P. Salazar-Mather, C.A. Biron, W.A. Kuziel, and E.G. Pamer. TNF/iNOS producing dendritic cells (Tip-DCs) mediate innate immune defense against bacterial infection. Immunity, 19:59-70, 2003.(2003)
• Dalod, M., T. Hamilton, R. Salomon, T.P. Salazar-Mather, S. Henry, and C.A. Biron. Dendritic cell responses to early murine cytomegalovirus infection: subset functional specialization and differential regulation by IFN-α/β. J. Exp. Med.197:885-898, 2003.(2003)
• Salazar-Mather, T.P. and K.L. Hokeness. Calling in the troops: Regulation of inflammatory cell trafficking through innate cytokine/chemokine networks. Invited Review Viral Immunol., 16:291-306, 2003.(2003)
• Dalod, M., T.P. Salazar-Mather, L. Malmgaard, C.A. Lewis, and C.A. Biron. IFN-α/β and IL-12 responses to viral infections: Pathways regulating dendritic cell cytokine expression in vivo. J. Exp. Med. 195:517-528, 2002.(2002)
• Nguyen, K.B., T.P. Salazar-Mather, M.Y. Dalod, J.E. Durbin, and C.A. Biron. Coordinated and distinct roles of NK cell responses to viral infection. J. Immunol. 169:4279-4287, 2002.(2002)
• Salazar-Mather, T.P., C.A. Lewis, and C.A. Biron. Type 1 interferons regulate inflammatory cell trafficking and macrophage inflammatory protein 1αdelivery to the liver. J. Clin. Invest. 110:321-330, 2002.(2002)
• Malmgarrd, L., T.P. Salazar-Mather, C.A. Lewis, and C.A. Biron. Pathways to IFN-α/β induction in vivo during viral infection. J. Virol. 76:4520-4525, 2002.(2002)
• Su, H.S., K.B. Nguyen, T.P. Salazar-Mather, M.C. Ruzek, M.Y. Dalod, and C.A. Biron. NK cell functions restrain T cell responses during viral infection. Eur. J. Immunol. 31:3048-3055, 2001.(2001)
• Salazar-Mather, T.P., T.A. Hamilton, and C.A. Biron. A chemokine-to-cytokine-to-chemokine cascade critical in antiviral defense. J. Clin. Invest. 105:985-993, 2000.(2000)
• Biron, C.A., K.B. Nguyen, G.C. Pien, L.P. Cousens, and T.P. Salazar-Mather. Natural killer cells in antiviral defense: Function and regulation by innate cytokines. Annu. Rev. Immunol. 17:189-220, 1999.(1999)
• Biron, C.A., L.P. Cousens, M.C. Ruzek, H.C. Su, and T.P. Salazar-Mather. Early cytokine responses to viral infections and their roles in shaping endogenous cellular immunity. Adv. Exp. Med. Biol. 452:143-149, 1998.(1998)
• Salazar-Mather, T.P., J.S. Orange, and C.A. Biron. Early murine cytomegalovirus infection induces liver natural killer cell inflammation and protection through MIP-1α-dependent pathways. J. Exp. Med. 187:1-14, 1998. Photography from this paper was selected for issue cover.(1998)
• Orange, J.S., T.P. Salazar-Mather, S.M. Opal, and C.A. Biron. Mechanisms for virus-induced liver disease: a TNF-mediated pathology independent of NK and T cells during murine cytomegalovirus infection. J. Virol. 171:9248-9258, 1997.(1997)
• Salazar-Mather, T.P., R. Ishikawa, and C.A. Biron. Natural killer (NK) cell trafficking and cytokine expression in splenic compartments after IFN-induction and viral infection. J. Immunol. 157:3054-3064, 1996.(1996)
• Orange, J.S., T.P. Salazar-Mather, S.M. Opal, S.F. Wolf, R.L. Spencer, A.H. Miller, B.S. McEwen, and C. A. Biron. Mechanisms of IL-12-mediated toxicities during experimental viral infections:role of TNF and glucocorticoids. J. Exp. Med. 181:901-914, 1995.(1995)