Aron E Lukacher, MD, PhD

Immunology
Microbial Pathogenesis

Professor
Pathology & Laboratory Medicine

Pathology Division(s):
Anatomic Pathology
Experimental Pathology

Email Address:
alukach@emory.edu

Education:

B.A.   Brandeis University, 1976 - 1980

M.D., Ph.D.   Washington University School of Medicine, 1980 - 1987

Research Interests:

- Immune response to infection by oncogenic DNA viruses
Our laboratory studies the immune response to infection by oncogenic DNA viruses. We use the well-characterized polyoma virus-mouse model. Polyoma virus, a natural mouse DNA virus, is arguably the most potent experimental oncogenic pathogen known. A major focus of our work is to elucidate mechanisms controlling induction, regulation, and maintenance of effective immunosurveillance against virus-induced neoplasia. Because oncogenic viruses persistently infect their hosts, we are also interested in understanding the programming of polyoma-specific memory T cell responses in the setting of chronic encounter with viral antigens. These studies have important implications for development of vaccines to persistently infecting viruses. Most humans are persistently infected by polyomaviruses which can have devastating consequences in immunocompromised individuals. In collaboration with Drs. Larsen and Newell (Dept. Surgery, Emory Univ), we have developed a kidney transplant mouse model to investigate the pathogenesis of polyomavirus-associated nephropathy, a leading cause of kidney transplant failure. The goal of our research is to develop strategies to manipulate the T cell response to polyoma virus to reverse susceptibility to virus-induced tumorigenesis and prevent kidney transplant rejection.

Clinical Focus:

Autopsy Pathology

Cardiac Pathology

Honors / Awards:

Dean's Clinical Investigator Award, 2001-2004

Presidential Early Career Award for Scientists and Engineers, 1996

Postdoctoral NIH Individual National Research Service Award, 1989-1991

Medical Scientist Training Program NIH Fellowship, 1980-1987

Molly W. and Charles K. Schiff Memorial Award in Science, 1980

Shalom Award to encourage original research in the undergraduate student body, 1980

Summa Cum Laude with High Honors in Biochemistry, 1980

Phi Beta Kappa, 1979

New York State Regents Scholarship, 1976

Specialty Boards:

1988 Diplomate National Board of Medical Examiners

1992 Diplomate Anatomic Pathology

Selected Publications:

Published and Accepted Research Articles -

Kemball, C.C., E.D.H. Lee, E. Szomolanyi-Tsuda, T.C. Pearson, C.P. Larsen, and A.E. Lukacher. 2006. Costimulation requirements for antiviral CD8+ T cells differs for acute and persistent phases of polyoma virus infection. J. Immunol., in press.

Lee, E.D.H., C.C. Kemball, J. Wang, Y. Dong, D.C. Stapler, Jr., K.M. Hamby, K.A. Newell, T.C. Pearson, A.E. Lukacher, and C.P. Larsen. 2006. A mouse model for polyomavirus-associated nephropathy of kidney transplants. Am. J. Transplant., in press.

Kumar, S., M.J. Skeen, Y. Adiri, H. Yoon, V.D. Vezys, A.E. Lukacher, B.D. Evavold, H.K. Ziegler, and J.M. Boss. 2006. A cytokine promoter/yellow fluorescent protein reporter transgene serves as an early activation marker of lymphocyte subsets. Cell. Immunol., in press.

Kemball, C.C., E.D.H. Lee, V.Vezys, T.C. Pearson, C.P. Larsen, and A.E. Lukacher. 2005. Late priming and variability in epitope-specific CD8+ T cell responses during a persistent virus infection. J. Immunol.174:7590-7960.

Kambayashi, T., E. Assarsson, A.E. Lukacher, H.-G. Ljunggren, and P.E. Jensen. 2003. Memory CD8+ T cells provide an early source of IFN-¿. J. Immunol. 170:2399-2408.

Byers, A.M., C.C. Kemball, J.M. Moser, and A.E. Lukacher. 2003. Cutting Edge: Rapid in vivo CTL activity by polyoma virus-specific effector and memory CD8+ T cells. J. Immunol., 171:17-21.

Moser, J.M., J. Gibbs, P.E. Jensen, and A.E. Lukacher. 2002. CD94/NKG2A receptors regulate antiviral CD8+ T cell responses. Nature Immunol. 3:189-195.

Shirasugi, N., A.B. Adams, M.M. Durham, A.E. Lukacher, H. Xu, P. Rees, S.R. Cowan, M.A. Williams, T.C. Pearson, and C.P. Larsen. 2002. Prevention of chronic rejection in murine cardiac allografts: a comparison of chimerism- and nonchimerism-inducing costimulation blockade-based tolerance induction regimens. J. Immunol. 169:2677-2684.

Drake III, D.R., M.L. Shawver, A. Hadley, E. Butz, C. Maliszewski, and A.E. Lukacher. 2001. Induction of polyoma virus-specific CD8+ T lymphocytes by distinct dendritic cell subpopulations. J. Virol. 75:544-547.

Moser, J.M., J.D. Altman, and A.E. Lukacher. 2001. Antiviral CD8+ T cell responses in neonatal mice: susceptibility to polyoma virus-induced tumors is associated with lack of cytotoxic function by viral antigen-specific T cells. J. Exp. Med. 193:595-605.

Daniels, M.A., J.D. Miller, J.M. Moser, L. Devine, P. Kavathas, A.E. Lukacher, J.D. Altman, and S.C. Jameson. 2001. CD8 binding to MHC class I molecules is influenced by T cell maturation and glycosylation. Immunity 15:1051-1061.

Drake III, D.R., J.M. Moser, A. Hadley, J.D. Altman, C. Maliszewski, E. Butz, and A.E. Lukacher. 2000. Polyomavirus-infected dendritic cells induce antiviral CD8+ T lymphocytes. J. Virol. 74:4093-4101.

Drake III, D.R., L. Knoepp, J. K. Actor, and A.E. Lukacher. 2000. Patterns of expression of viral and cytokine transcripts during mouse polyoma virus infection. Combinatorial Chemistry & High Throughput Screening 3:329-341.

Lukacher, A.E., J.M. Moser, A. Hadley, and J.D. Altman. 1999. Visualization of polyoma virus-specific CD8+ T cells in vivo during infection and tumor rejection. J. Immunol. 163:3369-3378.

Wilson, C.S., J.M. Moser, P.E. Jensen, J.D. Altman, and A.E. Lukacher. 1999. Cross-recognition of two middle T protein epitopes by immunodominant polyoma virus-specific CTL. J. Immunol. 162:3933-3941.

Lukacher, A.E. and C.S. Wilson. 1998. Resistance to polyoma virus-induced tumors correlates with CTL recognition of an immunodominant H-2Dk-restricted epitope in the middle T protein. J. Immunol. 160:1724-1734.

Hennigar, R., M. Pochet, D. Hunt, A. Lukacher, V. Venema, E. Seal, and M. Marrero. 1998. Phosphorylation of fatty acid synthase in mouse and human breast cancer cell lines. Biochem. Biophy. Acta 1392:85-100.

Jensen, P.E., J.C. Moore, and A.E. Lukacher. 1998. A europium fluoroimmunoassay for measuring peptide binding to MHC class I molecules. J. Immunol. Methods 21:71-80.

Drake III, D.R., and A.E. Lukacher. 1998. ¿2-microglobulin knockout mice are highly susceptible to polyoma virus tumorigenesis. Virology 252:275-284.

Lukacher, A.E.,Y. Ma, J.P. Carroll, S.R. Abromson-Leeman, J.C. Laning, M.E. Dorf, and T.L. Benjamin. 1995. Susceptibility to tumors induced by polyoma virus is conferred by an endogenous mouse mammary tumor virus superantigen. J. Exp. Med. 181:1683-1692.

Lukacher, A.E., R. Freund, J.P. Carroll, R.T. Bronson, and T.L. Benjamin. 1993. PyvS: A dominantly acting gene in C3H/BiDa mice conferring susceptibility to tumor induction by polyoma virus. Virology 196:241-248.

McDermott, M.R., A.E. Lukacher, V.L. Braciale, T.J. Braciale, and J. Bienenstock. 1987. Characterization and in vivo distribution of influenza-virus-specific T-lymphocytes in the murine respiratory tract. Am. Rev. Respir. Dis. 135:245-249.

Morrison, L.A., A.E. Lukacher, V.L. Braciale, D.P. Fan, and T.J. Braciale. 1986. Differences in antigen presentation to MHC class I- and class II-restricted influenza virus-specific cytolytic T lymphocyte clones. J. Exp. Med. 163:903-921.

Braciale, T.J., T.J. Henkel, A. Lukacher, and V.L. Braciale. 1986. Fine specificity and antigen receptor expression among influenza virus-specific cytolytic T lymphocyte clones. J. Immunol. 137:995-1002.

Lukacher, A.E., L.A. Morrison, V.L. Braciale, B. Malissen, and T.J. Braciale. 1985. Expression of specific cytolytic activity by H-2I region-restricted, influenza virus-specific T lymphocyte clones. J. Exp. Med. 162:171-187.

Lukacher, A.E., V.L. Braciale, and T.J. Braciale. 1984. In vivo effector function of influenza virus-specific cytotoxic T lymphocyte clones is highly specific. J. Exp. Med. 160:814-826.

Segal, G.B., A. Lukacher, B.R. Gordon, and M.A. Lichtman. 1980. Glucocorticoid suppression of human lymphocyte DNA synthesis: influence of phytohemagglutinin concentration. J. Lab. Clin. Med. 95:624-632.

Book Chapters -

Lukacher, A.E. 1999. Polyomavirus. In Persistent Viral Infections. R. Ahmed and I. Chen, eds. John Wiley & Sons, Ltd. New York, p.117-130.

Lukacher, A.E., L.A. Morrison, V.L. Braciale, and T.J. Braciale. 1986. T lymphocyte function in recovery from experimental viral infection: the influenza model. In Mechanisms of Host Resistance to Infectious Agents, Tumors, and Allografts. R.M. Steinman and R.J. North, eds. The Rockefeller University Press: New York. pp. 233-254.

Braciale, T.J., A.E. Lukacher, L. Morrison, and V.L. Braciale. 1985. Viral antigen recognition by CTL of different subsets. Cold Spring Harbor Current Communication in Molecular Biology. W.G. Laver and G.M. Air, eds. Cold Spring Harbor Press: New York. pp. 113-117.

Other Publications -

Lukacher, A.E. 2004. Pathogen-host standoff: Immunity to polyomavirus infection and neoplasia. Immunol. Res. 29:139-150.

Byers, A.M., C.C. Kemball, N.P. Andrews, and A.E. Lukacher. 2003. Regulation of antiviral CD8+ T cells by inhibitory natural killer cell receptors. Microbes and Infection 5:169-177.

Moser, J.M., A.M. Byers, and A.E. Lukacher. 2002. NK cell receptors in antiviral immunity. Curr. Op. Immunol. 14:509-516.

Lukacher, A.E. 2002. IFN-¿ suspends the killing license of anti-tumor CTLs. J. Clin. Invest. 110:1407-1409.

Moser, J.M. and A.E. Lukacher. 2001. Immunity to polyoma virus infection and tumorigenesis. Viral Immunol. 14:199-216.