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Aron E. Lukacher

TitleProfessor
InstitutionCollege of Medicine
DepartmentMicrobiology and Immunology
Address500 University Drive, Hershey, PA 17033
Phone7175316521
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    Collapse Overview 
    Collapse overview
    Education:
    1976-1980 Brandeis University, Waltham, MA
    Honors Thesis Mentor: David Freifelder, Ph.D.

    1980-1987 M.D., Ph.D., Medical Scientist Training Program,
    Washington University School of Medicine, St. Louis, MO
    Predoctoral Mentor: Thomas J. Braciale, M.D., Ph.D.

    Postgraduate Training:
    1987-1989 Dept. Pathology, Brigham and Women’s Hospital, Resident in Anatomic Pathology

    1989-1994 Dept. Pathology, Harvard Medical School, Research Fellow
    Postdoctoral Mentor: Thomas L. Benjamin, Ph.D.


    Research Interests:
    A major focus of our group is to understand the host immunological mechanisms needed to contain low-level persistent virus infections. For these studies, we predominantly use the mouse polyomavirus infection model. Our lab has developed state of the art immunological reagents and virological techniques to study T cell responses at different stages of mouse polyomavirus infection. Using these methodologies, we are defining at both cellular and molecular levels the mechanisms that regulate antiviral T cell function and fate. Polyomaviruses ubiquitously infect many vertebrate species, including humans, where they establish clinically silent lifelong infection in healthy hosts. In immunocompromised individuals, these viruses cause life threatening diseases. One of these viruses causes a fatal CNS demyelinating disease, whose incidence is rising in patients receiving immunomodulatory therapies for autoimmune diseases. Polyomaviruses are species specific, and no effective antiviral agents are available. A second major effort in our laboratory is to use mouse polyomavirus to understand the pathogenesis of this CNS disease and use it as a preclinical model to evaluate novel therapeutic compounds.



    Collapse Bibliographic 
    Collapse selected publications
    Publications listed below are automatically derived from MEDLINE/PubMed and other sources, which might result in incorrect or missing publications. Faculty can login to make corrections and additions.
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    1. Maru S, Jin G, Desai D, Amin S. Inhibition of Retrograde Transport Limits Polyomavirus Infection In Vivo. mSphere. 2017 Nov-Dec; 2(6). PMID: 29152583.
      View in: PubMed
    2. Maintenance of PD-1 on brain-resident memory CD8 T cells is antigen independent. Immunol Cell Biol. 2017 Nov; 95(10):953-959. PMID: 28829048.
      View in: PubMed
    3. Kim SC, Wang J, Dong Y, Mathews DV, Albrecht JA, Breeden CP, Farris AB, Lukacher AE, Ford ML, Newell KA, Adams AB. Alloimmunity But Not Viral Immunity Promotes Allograft Loss in a Mouse Model of Polyomavirus-Associated Allograft Injury. Transplant Direct. 2017 Jun; 3(6):e161. PMID: 28620645.
      View in: PubMed
    4. Qin Q, Lauver M, Maru S, Lin E, Lukacher AE. Reducing persistent polyomavirus infection increases functionality of virus-specific memory CD8 T cells. Virology. 2017 02; 502:198-205. PMID: 28063344.
      View in: PubMed
    5. Qin Q. Type I Interferons Regulate the Magnitude and Functionality of Mouse Polyomavirus-Specific CD8 T Cells in a Virus Strain-Dependent Manner. J Virol. 2016 05 15; 90(10):5187-99. PMID: 26984726; PMCID: PMC4859723 [Available on 10/29/16].
    6. Frost EL, Kersh AE, Evavold BD, Lukacher AE. Cutting Edge: Resident Memory CD8 T Cells Express High-Affinity TCRs. J Immunol. 2015 Oct 15; 195(8):3520-4. PMID: 26371252; PMCID: PMC4592826 [Available on 10/15/16].
    7. Badell IR, Kitchens WH, Wagener ME, Lukacher AE, Larsen CP, Ford ML. Pathogen Stimulation History Impacts Donor-Specific CD8(+) T Cell Susceptibility to Costimulation/Integrin Blockade-Based Therapy. Am J Transplant. 2015 Dec; 15(12):3081-94. PMID: 26228897.
      View in: PubMed
    8. Soni C, Domeier PP, Wong EB. Distinct and synergistic roles of Fc?RIIB deficiency and 129 strain-derived SLAM family proteins in the development of spontaneous germinal centers and autoimmunity. J Autoimmun. 2015 Sep; 63:31-46. PMID: 26162758; PMCID: PMC4564365.
    9. Frost EL, Lukacher AE. The importance of mouse models to define immunovirologic determinants of progressive multifocal leukoencephalopathy. Front Immunol. 2014; 5:646. PMID: 25601860; PMCID: PMC4283601.
    10. Hofstetter AR, Evavold BD, Lukacher AE. Peptide immunization elicits polyomavirus-specific MHC class ib-restricted CD8 T cells in MHC class ia allogeneic mice. Viral Immunol. 2013 Feb; 26(1):109-13. PMID: 23374150; PMCID: PMC3578367.
    11. Wilson JJ, Pack CD, Lin E, Frost EL, Albrecht JA, Hadley A, Hofstetter AR, Tevethia SS, Schell TD, Lukacher AE. CD8 T cells recruited early in mouse polyomavirus infection undergo exhaustion. J Immunol. 2012 May 01; 188(9):4340-8. PMID: 22447978; PMCID: PMC3331907.
    12. Albrecht JA, Dong Y, Wang J, Breeden C, Farris AB, Lukacher AE, Newell KA. Adaptive immunity rather than viral cytopathology mediates polyomavirus-associated nephropathy in mice. Am J Transplant. 2012 Jun; 12(6):1419-28. PMID: 22420885; PMCID: PMC3365603.
    13. Hofstetter AR, Ford ML, Sullivan LC, Wilson JJ, Hadley A, Brooks AG, Lukacher AE. MHC class Ib-restricted CD8 T cells differ in dependence on CD4 T cell help and CD28 costimulation over the course of mouse polyomavirus infection. J Immunol. 2012 Apr 01; 188(7):3071-9. PMID: 22393155; PMCID: PMC3311765.
    14. Shen XZ, Billet S, Lin C, Okwan-Duodu D, Chen X, Lukacher AE, Bernstein KE. The carboxypeptidase ACE shapes the MHC class I peptide repertoire. Nat Immunol. 2011 Oct 02; 12(11):1078-85. PMID: 21964607; PMCID: PMC3197883.
    15. Desmarets M, Mylvaganam G, Waller EK, Josephson CD, Pack C, Lukacher AE, Zimring JC. Minor antigens on transfused RBCs crossprime CD8 T cells but do not induce full effector function. Am J Transplant. 2011 Sep; 11(9):1825-34. PMID: 21884408; PMCID: PMC4284100.
    16. Wilson JJ, Lin E, Pack CD, Frost EL, Hadley A, Swimm AI, Wang J, Dong Y, Breeden CP, Kalman D, Newell KA, Lukacher AE. Gamma interferon controls mouse polyomavirus infection in vivo. J Virol. 2011 Oct; 85(19):10126-34. PMID: 21775464; PMCID: PMC3196421.
    17. Hofstetter AR, Sullivan LC, Lukacher AE, Brooks AG. Diverse roles of non-diverse molecules: MHC class Ib molecules in host defense and control of autoimmunity. Curr Opin Immunol. 2011 Feb; 23(1):104-10. PMID: 20970974; PMCID: PMC4254846.
    18. Rouse BT, Lukacher AE. Some unmet challenges in the immunology of viral infections. Discov Med. 2010 Oct; 10(53):363-70. PMID: 21034678; PMCID: PMC3884557.
    19. Lin E, Kemball CC, Hadley A, Wilson JJ, Hofstetter AR, Pack CD, Lukacher AE. Heterogeneity among viral antigen-specific CD4+ T cells and their de novo recruitment during persistent polyomavirus infection. J Immunol. 2010 Aug 01; 185(3):1692-700. PMID: 20622115; PMCID: PMC3642206.
    20. Ganusov VV, Lukacher AE, Byers AM. Persistence of viral infection despite similar killing efficacy of antiviral CD8(+) T cells during acute and chronic phases of infection. Virology. 2010 Sep 15; 405(1):193-200. PMID: 20580390; PMCID: PMC2922917.
    21. Swimm AI, Bornmann W, Jiang M, Imperiale MJ, Lukacher AE, Kalman D. Abl family tyrosine kinases regulate sialylated ganglioside receptors for polyomavirus. J Virol. 2010 May; 84(9):4243-51. PMID: 20181697; PMCID: PMC2863717.
    22. Hudson KE, Lin E, Hendrickson JE, Lukacher AE, Zimring JC. Regulation of primary alloantibody response through antecedent exposure to a microbial T-cell epitope. Blood. 2010 May 13; 115(19):3989-96. PMID: 20086249; PMCID: PMC2869558.
    23. Swanson PA, Hofstetter AR, Wilson JJ, Lukacher AE. Cutting edge: shift in antigen dependence by an antiviral MHC class Ib-restricted CD8 T cell response during persistent viral infection. J Immunol. 2009 May 01; 182(9):5198-202. PMID: 19380764; PMCID: PMC2861783.
    24. Sullivan CS, Sung CK, Pack CD, Grundhoff A, Lukacher AE, Benjamin TL, Ganem D. Murine Polyomavirus encodes a microRNA that cleaves early RNA transcripts but is not essential for experimental infection. Virology. 2009 Apr 25; 387(1):157-67. PMID: 19272626; PMCID: PMC2722155.
    25. Swanson PA, Lukacher AE, Szomolanyi-Tsuda E. Immunity to polyomavirus infection: the polyomavirus-mouse model. Semin Cancer Biol. 2009 Aug; 19(4):244-51. PMID: 19505652; PMCID: PMC2694952.
    26. Swanson PA, Pack CD, Hadley A, Wang CR, Stroynowski I, Jensen PE, Lukacher AE. An MHC class Ib-restricted CD8 T cell response confers antiviral immunity. J Exp Med. 2008 Jul 07; 205(7):1647-57. PMID: 18541714; PMCID: PMC2442642.
    27. Andrews NP, Pack CD, Lukacher AE. Generation of antiviral major histocompatibility complex class I-restricted T cells in the absence of CD8 coreceptors. J Virol. 2008 May; 82(10):4697-705. PMID: 18337581; PMCID: PMC2346753.
    28. Shen XZ, Lukacher AE, Billet S, Williams IR, Bernstein KE. Expression of angiotensin-converting enzyme changes major histocompatibility complex class I peptide presentation by modifying C termini of peptide precursors. J Biol Chem. 2008 Apr 11; 283(15):9957-65. PMID: 18252713; PMCID: PMC2442301.
    29. Kemball CC, Szomolanyi-Tsuda E, Lukacher AE. Allogeneic differences in the dependence on CD4+ T-cell help for virus-specific CD8+ T-cell differentiation. J Virol. 2007 Dec; 81(24):13743-53. PMID: 17913814; PMCID: PMC2168883.
    30. Kemball CC, Pack CD, Guay HM, Li ZN, Steinhauer DA, Szomolanyi-Tsuda E, Lukacher AE. The antiviral CD8+ T cell response is differentially dependent on CD4+ T cell help over the course of persistent infection. J Immunol. 2007 Jul 15; 179(2):1113-21. PMID: 17617604.
      View in: PubMed
    31. Andrews NP, Pack CD, Vezys V, Barber GN, Lukacher AE. Early virus-associated bystander events affect the fitness of the CD8 T cell response to persistent virus infection. J Immunol. 2007 Jun 01; 178(11):7267-75. PMID: 17513776.
      View in: PubMed
    32. Byers AM, Hadley A, Lukacher AE. Protection against polyoma virus-induced tumors is perforin-independent. Virology. 2007 Feb 20; 358(2):485-92. PMID: 17011010; PMCID: PMC2861337.
    33. Vezys V, Masopust D, Kemball CC, Barber DL, O'Mara LA, Larsen CP, Pearson TC, Ahmed R, Lukacher AE. Continuous recruitment of naive T cells contributes to heterogeneity of antiviral CD8 T cells during persistent infection. J Exp Med. 2006 Oct 02; 203(10):2263-9. PMID: 16966427; PMCID: PMC2118117.
    34. Byers AM, Andrews NP, Lukacher AE. CD94/NKG2A expression is associated with proliferative potential of CD8 T cells during persistent polyoma virus infection. J Immunol. 2006 May 15; 176(10):6121-9. PMID: 16670321.
      View in: PubMed
    35. Han Lee ED, Kemball CC, Wang J, Dong Y, Stapler DC, Hamby KM, Gangappa S, Newell KA, Pearson TC, Lukacher AE, Larsen CP. A mouse model for polyomavirus-associated nephropathy of kidney transplants. Am J Transplant. 2006 May; 6(5 Pt 1):913-22. PMID: 16611327.
      View in: PubMed
    36. Kemball CC, Lee ED, Szomolanyi-Tsuda E, Pearson TC, Larsen CP, Lukacher AE. Costimulation requirements for antiviral CD8+ T cells differ for acute and persistent phases of polyoma virus infection. J Immunol. 2006 Feb 01; 176(3):1814-24. PMID: 16424212.
      View in: PubMed
    37. Kumar S, Skeen MJ, Adiri Y, Yoon H, Vezys VD, Lukacher AE, Evavold BD, Ziegler HK, Boss JM. A cytokine promoter/yellow fluorescent protein reporter transgene serves as an early activation marker of lymphocyte subsets. Cell Immunol. 2005 Oct; 237(2):131-40. PMID: 16405934.
      View in: PubMed
    38. Kemball CC, Lee ED, Vezys V, Pearson TC, Larsen CP, Lukacher AE. Late priming and variability of epitope-specific CD8+ T cell responses during a persistent virus infection. J Immunol. 2005 Jun 15; 174(12):7950-60. PMID: 15944301.
      View in: PubMed
    39. Lukacher AE. Pathogen-host standoff: immunity to polyomavirus infection and neoplasia. Immunol Res. 2004; 29(1-3):139-50. PMID: 15181277.
      View in: PubMed
    40. Byers AM, Kemball CC, Moser JM, Lukacher AE. Cutting edge: rapid in vivo CTL activity by polyoma virus-specific effector and memory CD8+ T cells. J Immunol. 2003 Jul 01; 171(1):17-21. PMID: 12816977.
      View in: PubMed
    41. Kambayashi T, Assarsson E, Lukacher AE, Ljunggren HG, Jensen PE. Memory CD8+ T cells provide an early source of IFN-gamma. J Immunol. 2003 Mar 01; 170(5):2399-408. PMID: 12594263.
      View in: PubMed
    42. Byers AM, Kemball CC, Andrews NP, Lukacher AE. Regulation of antiviral CD8+ T cells by inhibitory natural killer cell receptors. Microbes Infect. 2003 Feb; 5(2):169-77. PMID: 12650775.
      View in: PubMed
    43. Lukacher AE. IFN-gamma suspends the killing license of anti-tumor CTLs. J Clin Invest. 2002 Nov; 110(10):1407-9. PMID: 12438437; PMCID: PMC151825.
    44. Shirasugi N, Adams AB, Durham MM, Lukacher AE, Xu H, Rees P, Cowan SR, Williams MA, Pearson TC, Larsen CP. Prevention of chronic rejection in murine cardiac allografts: a comparison of chimerism- and nonchimerism-inducing costimulation blockade-based tolerance induction regimens. J Immunol. 2002 Sep 01; 169(5):2677-84. PMID: 12193741.
      View in: PubMed
    45. Moser JM, Byers AM, Lukacher AE. NK cell receptors in antiviral immunity. Curr Opin Immunol. 2002 Aug; 14(4):509-16. PMID: 12088687.
      View in: PubMed
    46. Moser JM, Gibbs J, Jensen PE, Lukacher AE. CD94-NKG2A receptors regulate antiviral CD8(+) T cell responses. Nat Immunol. 2002 Feb; 3(2):189-95. PMID: 11812997.
      View in: PubMed
    47. Daniels MA, Devine L, Miller JD, Moser JM, Lukacher AE, Altman JD, Kavathas P, Hogquist KA, Jameson SC. CD8 binding to MHC class I molecules is influenced by T cell maturation and glycosylation. Immunity. 2001 Dec; 15(6):1051-61. PMID: 11754824.
      View in: PubMed
    48. Moser JM, Altman JD, Lukacher AE. 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. 2001 Mar 05; 193(5):595-606. PMID: 11238590; PMCID: PMC2193393.
    49. Moser JM, Lukacher AE. Immunity to polyoma virus infection and tumorigenesis. Viral Immunol. 2001; 14(3):199-216. PMID: 11572632.
      View in: PubMed
    50. Drake DR, Shawver ML, Hadley A, Butz E, Maliszewski C, Lukacher AE. Induction of polyomavirus-specific CD8(+) T lymphocytes by distinct dendritic cell subpopulations. J Virol. 2001 Jan; 75(1):544-7. PMID: 11119625; PMCID: PMC113949.
    51. Drake DR, Knoepp L, Lukacher AE, Actor JK. Patterns of expression of viral and cytokine gene transcripts during mouse polyoma virus infection. Comb Chem High Throughput Screen. 2000 Aug; 3(4):329-41. PMID: 10974145.
      View in: PubMed
    52. Drake DR, Moser JM, Hadley A, Altman JD, Maliszewski C, Butz E, Lukacher AE. Polyomavirus-infected dendritic cells induce antiviral CD8(+) T lymphocytes. J Virol. 2000 May; 74(9):4093-101. PMID: 10756021; PMCID: PMC111923.
    53. Lukacher AE, Moser JM, Hadley A, Altman JD. Visualization of polyoma virus-specific CD8+ T cells in vivo during infection and tumor rejection. J Immunol. 1999 Sep 15; 163(6):3369-78. PMID: 10477607.
      View in: PubMed
    54. Wilson CS, Moser JM, Altman JD, Jensen PE, Lukacher AE. Cross-recognition of two middle T protein epitopes by immunodominant polyoma virus-specific CTL. J Immunol. 1999 Apr 01; 162(7):3933-41. PMID: 10201912.
      View in: PubMed
    55. Drake DR, Lukacher AE. Beta 2-microglobulin knockout mice are highly susceptible to polyoma virus tumorigenesis. Virology. 1998 Dec 05; 252(1):275-84. PMID: 9875336.
      View in: PubMed
    56. Jensen PE, Moore JC, Lukacher AE. A europium fluoroimmunoassay for measuring peptide binding to MHC class I molecules. J Immunol Methods. 1998 Jun 01; 215(1-2):71-80. PMID: 9744749.
      View in: PubMed
    57. Hennigar RA, Pochet M, Hunt DA, Lukacher AE, Venema VJ, Seal E, Marrero MB. Characterization of fatty acid synthase in cell lines derived from experimental mammary tumors. Biochim Biophys Acta. 1998 May 20; 1392(1):85-100. PMID: 9593836.
      View in: PubMed
    58. Lukacher AE, Wilson CS. Resistance to polyoma virus-induced tumors correlates with CTL recognition of an immunodominant H-2Dk-restricted epitope in the middle T protein. J Immunol. 1998 Feb 15; 160(4):1724-34. PMID: 9469430.
      View in: PubMed
    59. Lukacher AE, Ma Y, Carroll JP, Abromson-Leeman SR, Laning JC, Dorf ME, Benjamin TL. Susceptibility to tumors induced by polyoma virus is conferred by an endogenous mouse mammary tumor virus superantigen. J Exp Med. 1995 May 01; 181(5):1683-92. PMID: 7722447; PMCID: PMC2191990.
    60. Lukacher AE, Freund R, Carroll JP, Bronson RT, Benjamin TL. Pyvs: a dominantly acting gene in C3H/BiDa mice conferring susceptibility to tumor induction by polyoma virus. Virology. 1993 Sep; 196(1):241-8. PMID: 8395116.
      View in: PubMed
    61. McDermott MR, Lukacher AE, Braciale VL, Braciale TJ, Bienenstock J. Characterization and in vivo distribution of influenza-virus-specific T-lymphocytes in the murine respiratory tract. Am Rev Respir Dis. 1987 Jan; 135(1):245-9. PMID: 2432811.
      View in: PubMed
    62. Braciale TJ, Henkel TJ, Lukacher A, Braciale VL. Fine specificity and antigen receptor expression among influenza virus-specific cytolytic T lymphocyte clones. J Immunol. 1986 Aug 01; 137(3):995-1002. PMID: 2424996.
      View in: PubMed
    63. Morrison LA, Lukacher AE, Braciale VL, Fan DP, Braciale TJ. Differences in antigen presentation to MHC class I-and class II-restricted influenza virus-specific cytolytic T lymphocyte clones. J Exp Med. 1986 Apr 01; 163(4):903-21. PMID: 3485173; PMCID: PMC2188068.
    64. Lukacher AE, Morrison LA, Braciale VL, Malissen B, Braciale TJ. Expression of specific cytolytic activity by H-2I region-restricted, influenza virus-specific T lymphocyte clones. J Exp Med. 1985 Jul 01; 162(1):171-87. PMID: 2409206; PMCID: PMC2187708.
    65. Lukacher AE, Braciale VL, Braciale TJ. In vivo effector function of influenza virus-specific cytotoxic T lymphocyte clones is highly specific. J Exp Med. 1984 Sep 01; 160(3):814-26. PMID: 6206190; PMCID: PMC2187390.
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