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Faculty Detail    
Name ALLAN J ZAJAC
 
Campus Address BBRB 446 Zip 2170
Phone 205-975-5644
E-mail azajac@uab.edu
Other websites Publications via Pubmed
     


Faculty Appointment(s)
Appointment Type Department Division Rank
Primary  Microbiology  Microbiology Associate Professor
Center  Arthritis & Musculoskeletal Diseases Center  Arthritis & Musculoskeletal Diseases Center Associate Professor
Center  Center for AIDS Research  Center for AIDS Research Associate Professor
Center  Comprehensive Cancer Center  Comprehensive Cancer Center Associate Professor

Graduate Biomedical Sciences Affiliations
Cellular and Molecular Biology Program 
Hughes Med-Grad Fellowship Program 
Immunology 
Medical Scientist Training Program 
Microbiology 
Pathobiology and Molecular Medicine 

Biographical Sketch 
Dr. Zajac completed his undergraduate studies in microbiology and virology at the University of Warwick, England (B.Sc with honors, 1991). For graduate studies he moved to the University of North Carolina at Chapel Hill (Ph.D, 1996) and then continued to pursue his interest in viral immunology as a Damon Runyon-Walter Winchell postdoctoral fellow in Rafi Ahmed's laboratory at Emory University. Allan was appointed as a Faculty member in the Department of Microbiology at UAB in November, 1999.

Research/Clinical Interest
Title
Anti-Viral Immunity; T Cell Responses; Immunological Memory
Description
Globally there are over 500 million citizens living with chronic HIV, hepatitis C, or hepatitis B virus infections and every year acute viral infections also cause significant disease, distress, and death. Thus, there is a critical need to develop better strategies to improve viral control and limit pathogenesis, that are ideally directed by an in-depth fundamental understanding of disease processes and host protection mechanisms. My research program is focused on immune responses to infection. I am fascinated by why certain infections and vaccines elicit robust and highly effective responses that can control the pathogen and subsequently provide life long protection, whereas during persistent infections these responses become corrupted. This corruption of the immune response can be catastrophic, resulting in failure to contain the infection, clinical complications, and increased likelihood of transmission. The majority of my research efforts involve investigating cell-mediated immune responses. Our studies have shown that virus-specific CD8 T cells succumb to exhaustion during chronic viral infections as they sequentially lose the typical arrays of effector functions that usually combat the infection. In published and ongoing studies we have used cytokine-reporter mice to track the ontogeny of T cell responses following viral infections. These studies have helped to define the origins of virus-specific memory CD4 T cells as well as the very early activation of anti-viral CD8 T cells which occurs during the first stages of a chronic viral infection. We are currently addressing the specific roles of functionally distinct subsets of T cell during acute and chronic infections and are pin-pointing which populations confer superior infection control and are most resistant to exhaustion. Many studies, including findings from my own laboratory, have highlighted the vital role for CD4 T cells in supporting CD8 T cell responses. Defining how these populations communicate and collaborate to drive strong anti-viral activities assists with devising strategies to improve inferior responses and understanding why immunity can erode. We discovered that the CD4 T cell derived cytokine IL-21 is essential for sustaining cell-mediated immunity in chronically infected hosts. We are now working towards defining exactly how this cytokine operates to support anti-viral T cell responses and exploring whether this can be therapeutically harnessed to boost immunity and improve viral control. Interactions between the cells of the immune system allows for the exchange of molecular information and commands which launch and regulate the individuals response to infections. We are also defining how adhesion molecules, which function to promote cellular interactions, shape the fate decisions of the responding T cells. We have shown that ablating specific adhesion molecule interactions can alter the magnitude, functional quality, and recall potential of anti-viral CD8 T cell responses. The next steps are now being taken to determine whether blocking these interactions is a viable therapeutic option for enhancing immune responses and better containing viral infections. Our studies generate fundamental information which is broadly applicable to understanding immunity to infections. Through a network of local and national collaborators we are continually expanding the scope of our studies. This includes exploring the roles of specific cytokines in developing and sustaining pathogenic autoimmune responses, such as inflammatory bowel disease, as well as examining the roles of cytokines and T cell responses during transplantation. We also have longstanding collaborations to better define how responses to chronic infections of humans, especially HIV infection, are regulated and subverted.

Selected Publications 
Publication PUBMEDID
Zajac, A., Blattman, J., Murali-Krishna, K., Sourdive, D., Suresh, M., Altman, J. & Ahmed R. (1998). Viral immune evasion due to persistence of activated T cells without effector function. Journal of Experimental Medicine 188, 2205-2213.  9858507 
Yi JS, Du M, Zajac AJ. (2009). A Vital Role for Interleukin-21 in the Control of a Chronic Viral Infection.
Science. May 14 
19443735 
Harrington LE, Janowski KM, Oliver JR, Zajac AJ, Weaver CT. (2008). Memory CD4 T cells emerge from effector T-cell progenitors. Nature 452, 356-360  18322463 
Wojciechowski, S., Jordan, M., Zhu, Y., White, J., Zajac, A. & Hildeman, D. (2006). Bim mediates apoptosis of CD127lo effector T cells and limits T cell memory. Eur. J. Immunol. Jun 8  16761315 
Tebo, A., Fuller, M., Gaddis, D., Kojima, K., Rehani, K. & Zajac, A. (2005). Rapid recruitment of CD8 T cells restructures immunodominance during recall responses. Journal of Virology 79, 12703-12713.  16188973 
Fuller, M., Hildeman, D., Sabbaj, S., Gaddis, D., Tebo, A., Shang, L., Goepfert, P. & Zajac, A. (2005). Cutting Edge: Emergence of CD127hi functionally competent memory T Cells is compromised by high viral loads and inadequate T cell help. Journal of Immunology 174, 4204-4214.  15879083 
Fuller, M., Khanolkar, A., Tebo, A., & Zajac, A. (2004). Maintenance, loss and resurgence of T cell responses during acute, protracted and chronic viral infections. Journal of Immunology 172, 4204-4214.  15034033 
Khanolkar, A., Fuller, M. & Zajac, A. (2004). CD4 T cell-dependent CD8 T cell maturation. Journal of Immunology 172, 2834-2844.  14978084 
Zajac, A., Dye, J. & Quinn, D. (2003). Control of lymphocytic choriomeningitis virus infection in granzyme B deficient mice. Virology 305, 1-9.  12504535 
Fuller, M. & Zajac, A. (2003). Ablation of CD8 and CD4 cell responses by high viral loads. Journal of Immunology 170, 477-86.  12496434 
Khanolkar, A., Fuller, M., Zajac, A. (2002). T cell responses to viral infections: Lessons from lymphocytic choriomeningitis virus. Immunologic Research 26, 309-321.  12403369 
McMahon, C., Zajac, A., Jamieson, A., Corral, L., Mammer, G., Ahmed, R., Raulet, D. (2002). Viral and bacterial infections induce expression of multiple NK cell receptors in responding CD8+ T cells. Journal of Immunology 169, 1444-1452.  12133970 
Puglielli, M., Zajac, A., van der Most, R., Dzuris, J., Sette, A., Altman, J. & Ahmed, R. (2001). In vivo selection of a lymphocytic choriomeningitis virus variant that affects recognition of the GP33-43 epitope by H-2Db but not H-2Kb. Journal of Virology 75, 5099-5107.  11333891 
Grayson, J., Zajac, A., Altman, J. & Ahmed, R. (2000). Increased expression of Bcl-2 in antigen specific memory CD8+ T cells. Journal of Immunology (Cutting Edge) 164, 3946-3954.  10754284 
Zajac, A., Vance, R., Held, W., Sourdive, D., Altman, J., Raulet, D. & Ahmed, R. (1999). Impaired anti-viral T-cell responses due to expression of the LY49A inhibitory receptor. Journal of Immunology 163, 5526-5534.  10553080 
Buchmeier, M. & Zajac, A. (1999). Lymphocytic choriomeningitis virus. In “Persistent Viral Infections”; R. Ahmed & I. Chen eds. John Wiley & Sons publishers. pp 575-605.   

Keywords
Immunology, Virology, Pathogenesis, Vaccines, T cells