Sebastian Joyce, Ph.D.

Professor

sebastian.joyce@vanderbilt.edu
Faculty Appointments
Professor of Pathology, Microbiology and Immunology Dorothy B. and Theodore R. Austin Chair in Pathology
Education
Ph.D., Microbiology&Immunology, Medical College of Virginia, Richmond, VirginiaM.Sc., Experimental Biology, Saurashtra University, Rajkot, IndiaB.Sc., Chemistry/Zoology/Botany, Bangalore University, Bangalore, India
Office Address
A-4223 MCN
TN 2363
Research Description
"ANTIGENS, ANTIGEN RECOGNITION BY T CELLS AND MUCOSAL IMMUNITY"

For detailed description, visit us at https://medschool.vanderbilt.edu/joyce-lab/

Sensation and actuation are fundamental to physiologic systems, which evolved to sense perturbations in homeostasis and actuate an appropriate response so as to restore a set homeostatic state unique to an organism. The immune system functions much like a sensor-actuator system akin to the nervous system. The immune system most times works rather quietly, unless o' course winter turns to spring--for those allergic begin coughing and sneezing and huffing and wheezing! So also, we have all felt the power of the immune system when recovering from an infectious disease or expulsing an intestinal worm or, alternatively, its wrath in those suffering autoimmune diseases. In all of these instances, the initiation of an immune response begins with sensing of an antigenic substance--this sensing is called immunologic recognition.

The focus of our research programme is on immunologic recognition that regulates T lymphocyte function in health and disease. This entails an in-depth understanding of (a) what T cells recognize during development and during an immune response; (b) how T cell antigens are processed and transported to cellular sites of assembly for presentation by MHC and MHC-like molecules; and (c) how antigen presentation leads to the induction of the proper immune response?

Our laboratory addresses these questions through three major projects: (a) large-scale pathogen-derived CD8 T cell epitope discovery and mechanisms of action of new generation, microbe-free mucosal vaccines; (b) mechanisms of peptide and lipid antigen processing and presentation; and (c) the molecular basis of NKT cell ontogeny and function. We take a systematic, multidisciplinary approach--immunologic, cell and molecular biologic, biochemical, proteomics and genomics--to address questions in these areas.
Research Keywords
IMMUNOLOGIC RECOGNITION: HOW T CELLS SEE ANTIGENS AND RESPOND TO REGULATE MUCOSAL IMMUNITY AND INFLAMMATION
Publications
Danielli S, Ma Z, Pantazi E, Kumar A, Demarco B, Fischer F, Paudel U, Weissenrieder J, Lee RJ, JOYCE S, Foskett JK, Bezbradica JS, et al. CALHM6 is an immunological synaptic channel-forming protein required for macrophage-natural killer cell communication upon infection. EMBO J. 2023 Apr; 42: e111450. DOI: 10.15252/embj.2022111450.

JOYCE S, et al. Cancer Antigens: Sources, Generation & Presentation. Handbook of Cancer & Immunology. 2023; DOI: 10.1007/978-3-030-80962-1_38-1.

JOYCE S, Okoye GD, Driver JP, et al. Die Kämpfe u´nd schla´chten—The Struggles and Battles of Innate-Like Effector T Lymphocytes with Microbes. Frontiers in Immunology. 2023; 14: in press. DOI: 10.3389/fimmu.2023.1117825.

Suryadevara N, Kumar A, Ye X, Rogers M, Williams JV, Wilson JT, Karijolich J, JOYCE S, et al. A molecular signature of lung-resident CD8+ T cells elicited by subunit vaccination. Scientific Reports. 2022 Nov 11/9/2022; 12: 19101. DOI: https://doi.org/10.1038/s41598-022-21620-7.

Postoak JL, Song W, Yang G, Guo X, Xiao S, Saffold CE, Zhang J, JOYCE S, Manley NR, Wu L, Van Kaer L, et al. Thymic epithelial cells require lipid kinase Vps34 for CD4 but not CD8 T cell selection. Journal of Experimental Medicine. 2022 Sep; 219: e20212554. DOI: https://doi.org/10.1084/jem.20212554.

JOYCE S, et al. Life in-between: bridging innate and adaptive immunity [editorial]. J Immunol. 2022 Jul 7/15/2022; 209: 193-5. DOI: https://doi.org/10.4049/jimmunol.2290012.

Gu H, Madrid DMC, S JOYCE, Driver JP, et al. A single-cell analysis of thymopoiesis and thymic iNKT cell development in pigs. Cell Reports. 2022 Jul 7/5/2022; 40: 111050. DOI: https://doi.org/10.1016/j.celrep.2022.111050.

Carson CS, Becker KW, Garland KM, Pagendarm HM, Stone PT, Arora K, Wang-Bishop L, Baljon JJ, Cruz LD, JOYCE S, Wilson JT, et al. A nanovaccine platform for enhancing cellular immunity via cytosolic co-delivery of antigen and immunostimulatory poly(IC) RNA. J Controlled Release. 2022 Feb; 345: 354-70. DOI: 10.1016/j.jconrel.2022.03.020.

Sharma J, Carson C, Douglas T, Wilson JT, JOYCE S, et al. Nano-particulate platforms for vaccine delivery to enhance antigen-specific CD8+ T cell response. Methods Mol Biol. 2022 Jan; 2412: 367-98. DOI: https://doi.org/10.1007/978-1-0716-1892-9_19.

JOYCE S, Okoye G.D., Van Kaer L, et al. Natural killer T lymphocytes integrate innate sensory information & relay context to effector immune responses. Crit Rev Immunol. 2021 Dec; 41: 55-88.

JOYCE S, Ternette Nicola, et al. Know thy immune self and non-self: Proteomics informs on the expanse of self and non-self, and how and where they arise. Proteomics. 2021 Nov; 21: DOI: 10.1002/pmic.202000143.

Miranda-Katz M, Erickson JJ, Lan J, Ecker A, Zhang Y, JOYCE S, Williams JV, et al. Novel HLA-B7-restricted human metapneumovirus epitopes enhance viral clearance in mice and are recognized by human CD8 + T cells. Sci Rep. 2021 Oct; 11: DOI: https://doi.org/10.1038/s41598-021-00023-0.

Shae Daniel, Baljon Jessalyn J., Wehbe Mohamed, Christov Plamen P., Becker Kyle W., Kumar Amrendra, Suryadevara Naveenchandra, Carson Carcia S., Palmer Christian R., Knight Frances C., JOYCE Sebastian, Wilson John T, et al. Co-delivery of peptide neoantigens and stimulator of interferon genes (STING) agonists enhances response to cancer vaccines. ACS Nano. 2020 Jul 7/23/2020; 14(in press): DOI: https://doi.org/10.1021/acsnano.0c02765.

Kumar A, Wilson JT, Suryadevara NC, DiPaolo RJ, Briien JD, JOYCE S, et al. Heterotypic immunity against vaccinia virus in an HLA-B*07:02 transgenic mousepox infection model. Scientific Reports. 2020 Jul; 10: 13167. DOI: https://doi.org/10.1038/s41598-020-69897-w.

Van Kaer Luc, JOYCE Sebastian, et al. Survivre et vivre: when iNKT cells met a Hippo [editorial]. J Exp Med. 2020 Jun 6/1/2020; 217(in press): DOI: https://doi.org/10.1084/jem.20200343.

Kumar A, Hill TM, Gordy LE, Suryadevara N, Wu L, Flyak AI, Bezbradica JS, Van Kaer L, JOYCE S, et al. Nur77 controls tolerance induction, terminal differentiation, and effector functions in semi-invariant natural killer T cells. Proc Natl Acad Sci USA. 2020 Jun; 117: 17156-65. DOI: https://doi-org.proxy.library.vanderbilt.edu/10.1073/pnas.2001665117.

Bezbradica Jelena, JOYCE Sebastian. NKT cells join the two step for inflammasome-independent IL-1beta release [editorial]. Cell Reports. 2020 Apr 4/7/2020; 31: 107481-1-107481-2. DOI: https://doi.org/10.1016/j.celrep.2020.03.045.

JOYCE Sebastian, Spiller Benjamin, Van Kaer Luc, et al. NKT CELLS: What one lipid giveth, another taketh away. Nature Immunol. 2019 Oct; 20: 1559-61.

Knight C, Gilchuk P, Kumar A, Becker K, Sevimli S, Jacobson ME, Suryadevera N, Wang-Bishop L, Boyd K, Crowe JE, JOYCE S, Wilson JT. Mucosal Immunization with a pH-Responsive Nanoparticle Vaccine Induces Protective CD8+ Lung-Resident Memory T Cells. ACS Nano. 2019 Sep 9/25/2019; 13: 10939-60. PMID: 31553872, DOI: 10.1021/acsnano.9b00326.

Rogers MC, Lamens KD, Shafagati N, Johnson M, Oury TD, Joyce S, Williams JV. CD4+ Regulatory T Cells Exert Differential Functions during Early and Late Stages of the Immune Response to Respiratory Viruses. J. Immunol [print-electronic]. 2018 Aug 8/15/2018; 201(4): 1253-66. PMID: 29997123, PMCID: PMC6089537, PII: jimmunol.1800096, DOI: 10.4049/jimmunol.1800096, ISSN: 1550-6606.

Yang J, Kumar A, Vilgelm AE, Chen SC, Ayers GD, Novitskiy SV, Joyce S, Richmond A. Loss of CXCR4 in Myeloid Cells Enhances Antitumor Immunity and Reduces Melanoma Growth through NK Cell and FASL Mechanisms. Cancer Immunol Res [print-electronic]. 2018 Aug 8/14/2018; PMID: 30108045, PII: 2326-6066.CIR-18-0045, DOI: 10.1158/2326-6066.CIR-18-0045, ISSN: 2326-6074.

Qiu F, Becker KW, Knight FC, Baljon JJ, Sevimli S, Shae D, Gilchuk P, Joyce S, Wilson JT. Poly(propylacrylic acid)-peptide nanoplexes as a platform for enhancing the immunogenicity of neoantigen cancer vaccines. Biomaterials [print-electronic]. 2018 Jul 7/30/2018; 182: 82-91. PMID: 30107272, PII: S0142-9612(18)30543-X, DOI: 10.1016/j.biomaterials.2018.07.052, ISSN: 1878-5905.

Kumar A, Suryadevara N, Hill TM, Bezbradica JS, Van Kaer L, JOYCE S, et al. Natural Killer T Cells: an ecological evolutionary developmental biology perspective. Frontiers in Immunology. 2017 Dec 12/7/2017; 8: 1858. DOI: 10.3389/fimmu.2017.01858.

Kumar A, Gordy LE, Bezbradica JS, Stanic AK, Hill TM, Boothby MR, Van Kaer L, JOYCE S, et al. NF-kB PROTECTS NKT CELLS FROM TUMOR NECROSIS FACTOR RECEPTOR 1-INDUCED DEATH. Scientific Reports. 2017 Nov 11/15/2017; 7: 15594.

Galassie AC, Goll JB, Samir P, Jensen TL, Hoek KL, Howard LM, Allos TM, Niu X, Gordy LE, Creech CB, Hill H, JOYCE S, Link AJ, Edwards KL, et al. Proteomics show antigen presentation processes in human immune cells after AS03-H5N1 vaccination. Proteomics. 2017 May 5/9/2017; 17: 1600453. doi: 10.1002/pmic.201600453.

Sevimli S, Knight FC, Gilchuk P, JOYCE S, Wilson JT, et al. Fatty acid-mimetic micelles for dual-delivery of antigens and imidazoquinoline adjuvants. ACS Biomater Sci Eng. 2017; 3: 179-94.

Kumar A, Bezbradica JS, Stanic AK, JOYCE S, et al. Characterization and Functional Analysis of Mouse Semi-invariant Natural Killer T Cells. Current Protocols in Immunology. 2017; 14.13.1-14.13.55.

Howard LM, Hoek KL, Goll JB, Samir P, Galassie A, Allos TM, Niu X, Gordy LE, Creech CB, Prasad N, Jensen TL, Hill H, Levy SE, JOYCE S, Link AJ, Edwards KM, et al. Cell-based systems biology analysis of AS03-adjuvanted H5N1 avian influenza vaccine in humans. PLoS ONE. 2017 Jan; 12: e0167488.

Gilchuk I, Gilchuk P, et alii, JOYCE S, Crowe JE, et al. Cross-neutralizing and protective human antibody specificities to poxvirus infections. Cell. 2016 Oct 10/21/2016; 167: 684-94.

Gilchuk P, Knight FC, Wilson JT, JOYCE Sebastian. Eliciting Epitope-Specific CD8+ T Cell Response by Immunization with Microbial Protein Antigens Formulated with a-Galactosylceramide: Theory, Practice, and Protocols. In: Vaccine Adjuvants: Methods and Protocols METHODS IN MOLECULAR BIOLOGY. 1494. New York (United States): Springer Science & Business Media, LLC; 2016 Oct 10/8/2016.p. 321-52.

Gilchuk P, Hill TM, Guy C, McMaster SR, Boyd KL, Rabacal WA, Lu P, Shyr Y, Kohlmeier JE, Sebzda E, Green D, JOYCE S, et al. A distinct lung interstitium-resident memory CD8+ T cell subset confers enhanced protection to lower respiratory tract infection. Cell Reports. 2016 Aug 8/16/2016; 16: 1800-9.

Hastings AK, Gilchuk P, Joyce S, Williams JV. Novel HLA-A2-restricted human metapneumovirus epitopes reduce viral titers in mice and are recognized by human T cells. Vaccine [print-electronic]. 2016 Apr 4/19/2016; PMID: 27105560, PII: S0264-410X(16)30175-X, DOI: 10.1016/j.vaccine.2016.04.034, ISSN: 1873-2518.

Hill TM, Bezbradica JS, Van Kaer L, JOYCE S. CD1d-Restricted Natural Killer T Cells. ELS. 2016 Mar.

Van Kaer Luc, Wu Lan, JOYCE Sebastian. Mechanisms and Consequences of Antigen Presentation by CD1. Trends in Immunology. 2016; 37: 738-54.

Li B, Siuta M, Bright V, Koktysh D, Matlock B, Dumas M, Zhu M, Holt A, Stec D, Deng S, Savage P, JOYCE S, Pham W, et al. Improved proliferation of antigen-specific cytolytic T lymphocytes using a multimodal nanovaccine. Int J Nanomed. 2016; 11: 1747-55.

Spencer CT, Bezbradica JS, Ramos MG, Arico CD, Conant SB, Gilchuk P, Gray JJ, Zheng M, Niu X, Hildebrand W, Link AJ, Joyce S. Viral infection causes a shift in the self peptide repertoire presented by human MHC class I molecules. Proteomics Clin Appl. 2015 Dec; 9(11-12): 1035-52. PMID: 26768311, DOI: 10.1002/prca.201500106, ISSN: 1862-8354.

Joyce S. Immunoproteasomes edit tumors, which then escapes immune recognition. Eur. J. Immunol [print-electronic]. 2015 Dec; 45(12): 3241-5. PMID: 26527367, PMCID: PMC4695966, DOI: 10.1002/eji.201546100, ISSN: 1521-4141.

Erickson JJ, Lu P, Wen S, Hastings AK, Gilchuk P, Joyce S, Shyr Y, Williams JV. Acute Viral Respiratory Infection Rapidly Induces a CD8+ T Cell Exhaustion-like Phenotype. J. Immunol [print-electronic]. 2015 Nov 11/1/2015; 195(9): 4319-30. PMID: 26401005, PMCID: PMC4733528, PII: jimmunol.1403004, DOI: 10.4049/jimmunol.1403004, ISSN: 1550-6606.

Stengel KR, Zhao Y, Klus NJ, Kaiser JF, Gordy LE, Joyce S, Hiebert SW, Summers AR. Histone Deacetylase 3 Is Required for Efficient T Cell Development. Mol. Cell. Biol [print-electronic]. 2015 Nov; 35(22): 3854-65. PMID: 26324326, PMCID: PMC4609739, PII: MCB.00706-15, DOI: 10.1128/MCB.00706-15, ISSN: 1098-5549.

Wen SC, Schuster JE, Gilchuk P, Boyd KL, Joyce S, Williams JV. Lung CD8+ T Cell Impairment Occurs during Human Metapneumovirus Infection despite Virus-Like Particle Induction of Functional CD8+ T Cells. J. Virol [print-electronic]. 2015 Sep; 89(17): 8713-26. PMID: 26063431, PMCID: PMC4524081, PII: JVI.00670-15, DOI: 10.1128/JVI.00670-15, ISSN: 1098-5514.

Hill TM, Gilchuk P, Cicek BB, Osina MA, Boyd KL, Durrant DM, Metzger DW, Khanna KM, Joyce S. Border Patrol Gone Awry: Lung NKT Cell Activation by Francisella tularensis Exacerbates Tularemia-Like Disease. PLoS Pathog. 2015 Jun; 11(6): e1004975. PMID: 26068662, PMCID: PMC4465904, PII: PPATHOGENS-D-15-00244, DOI: 10.1371/journal.ppat.1004975, ISSN: 1553-7374.

Gilchuk P, Hill TM, Wilson JT, Joyce S. Discovering protective CD8 T cell epitopes--no single immunologic property predicts it!. Curr. Opin. Immunol [print-electronic]. 2015 Jun; 34: 43-51. PMID: 25660347, PII: S0952-7915(15)00014-X, DOI: 10.1016/j.coi.2015.01.013, ISSN: 1879-0372.

Hastings AK, Erickson JJ, Schuster JE, Boyd KL, Tollefson SJ, Johnson M, Gilchuk P, Joyce S, Williams JV. Role of type I interferon signaling in human metapneumovirus pathogenesis and control of viral replication. J. Virol [print-electronic]. 2015 Apr; 89(8): 4405-20. PMID: 25653440, PMCID: PMC4442394, PII: JVI.03275-14, DOI: 10.1128/JVI.03275-14, ISSN: 1098-5514.

Hoek, KL, Samir, P, Niu, X, Howard, LM, Prasad, N, Galassie, A, Liu, Q, Allos, TM, Guo, Y, Shyr, Y, Levy, S., Joyce, S, Edwards, KE, Link, AJ. A cell-based systems biology assessment of human blood to monitor immune responses following influenza vaccination. 2015.

Yang J, Hawkins OE, Barham W, Gilchuk P, Boothby M, Ayers GD, Joyce S, Karin M, Yull FE, Richmond A. Myeloid IKKß promotes antitumor immunity by modulating CCL11 and the innate immune response. Cancer Res [print-electronic]. 2014 Dec 12/15/2014; 74(24): 7274-84. PMID: 25336190, PMCID: PMC4349570, PII: 0008-5472.CAN-14-1091, DOI: 10.1158/0008-5472.CAN-14-1091, ISSN: 1538-7445.

Wen SC, Tollefson SJ, Johnson M, Gilchuk P, Boyd KL, Shepherd B, Joyce S, Williams JV. Acute clearance of human metapneumovirus occurs independently of natural killer cells. J. Virol [print-electronic]. 2014 Sep; 88(18): 10963-9. PMID: 24965465, PMCID: PMC4178848, PII: JVI.01558-14, DOI: 10.1128/JVI.01558-14, ISSN: 1098-5514.

Gilchuk P, Spencer CT, Conant SB, Hill T, Gray JJ, Niu X, Zheng M, Erickson JJ, Boyd KL, McAfee KJ, Oseroff C, Hadrup SR, Bennink JR, Hildebrand W, Edwards KM, Crowe JE, Williams JV, Buus S, Sette A, Schumacher TN, Link AJ, Joyce S. Discovering naturally processed antigenic determinants that confer protective T cell immunity. J. Clin. Invest [print-electronic]. 2013 May; 123(5): 1976-87. PMID: 23543059, PMCID: PMC3635741, PII: 67388, DOI: 10.1172/JCI67388, ISSN: 1558-8238.

Spencer CT, Dragovic SM, Conant SB, Gray JJ, Zheng M, Samir P, Niu X, Moutaftsi M, Van Kaer L, Sette A, Link AJ, Joyce S. Sculpting MHC class II-restricted self and non-self peptidome by the class I Ag-processing machinery and its impact on Th-cell responses. Eur. J. Immunol [print-electronic]. 2013 May; 43(5): 1162-72. PMID: 23386199, PMCID: PMC3798073, DOI: 10.1002/eji.201243087, ISSN: 1521-4141.

Erickson JJ, Gilchuk P, Hastings AK, Tollefson SJ, Johnson M, Downing MB, Boyd KL, Johnson JE, Kim AS, Joyce S, Williams JV. Viral acute lower respiratory infections impair CD8+ T cells through PD-1. J. Clin. Invest [print-electronic]. 2012 Aug; 122(8): 2967-82. PMID: 22797302, PMCID: PMC3408742, PII: 62860, DOI: 10.1172/JCI62860, ISSN: 1558-8238.

Spencer CT and Joyce S. Know thyself: variations in self peptidome and their immunologic consequences. ASHI Quarterly. 2012; 36(3): 28-36.

Gordy LE, Bezbradica JS, Flyak AI, Spencer CT, Dunkle A, Sun J, Stanic AK, Boothby MR, He YW, Zhao Z, Van Kaer L, Joyce S. IL-15 regulates homeostasis and terminal maturation of NKT cells. J. Immunol [print-electronic]. 2011 Dec 12/15/2011; 187(12): 6335-45. PMID: 22084435, PMCID: PMC3237743, PII: jimmunol.1003965, DOI: 10.4049/jimmunol.1003965, ISSN: 1550-6606.

Joyce S, Girardi E, Zajonc DM. NKT cell ligand recognition logic: molecular basis for a synaptic duet and transmission of inflammatory effectors. J. Immunol. 2011 Aug 8/1/2011; 187(3): 1081-9. PMID: 21772035, PMCID: PMC3166221, PII: 187/3/1081, DOI: 10.4049/jimmunol.1001910, ISSN: 1550-6606.

Dragovic SM, Hill T, Christianson GJ, Kim S, Elliott T, Scott D, Roopenian DC, Van Kaer L, Joyce S. Proteasomes, TAP, and endoplasmic reticulum-associated aminopeptidase associated with antigen processing control CD4+ Th cell responses by regulating indirect presentation of MHC class II-restricted cytoplasmic antigens. J. Immunol [print-electronic]. 2011 Jun 6/15/2011; 186(12): 6683-92. PMID: 21572029, PMCID: PMC3537507, PII: jimmunol.1100525, DOI: 10.4049/jimmunol.1100525, ISSN: 1550-6606.

Boelte KC, Gordy LE, Joyce S, Thompson MA, Yang L, Lin PC. Rgs2 mediates pro-angiogenic function of myeloid derived suppressor cells in the tumor microenvironment via upregulation of MCP-1. PLoS ONE. 2011; 6(4): e18534. PMID: 21494556, PMCID: PMC3073977, DOI: 10.1371/journal.pone.0018534, ISSN: 1932-6203.

Aiken C and Joyce S. TRIM5 does double duty [editorial]. Nature. 2011; 472: 305-6.

Gordy LE, Bezbradica JS, Flyak AI, Spencer CT, Dunkle A, Stanic A.K., Sun J, Boothby MR, He Y-W, Zhao Z, Van Kaer L, and Joyce S. IL-15 regulates homeostasis and terminal maturation of NKT cells. J Immunol. 2011; 187: 6335-45.

Spencer CT, G Pavlo, SM Dragovic and S Joyce. Minor histocompatibility antigens: presentation principles, recognition logic and the potential for a healing hand [editorial]. Current Opinion in Organ Transplantation. 2010; 15((4)): 512-25.

Joyce S and Gordy LE. Natural killer T cell-a cat o' nine lives! [editorial]. EMBO J. 2010; 29: 1475-6.

Lee K, Gudapati P, Dragovic S, Spencer C, Joyce S, Killeen N, Magnuson MA and Boothby M. Mammalian target of rapamycin protein complex 2 regulates differentiation of Th1 and Th2 cell subsets via distinct signaling pathways. Immunity. 2010; 32: 743-53.

Escande-Beillard N, Washburn L, Zekzer D, Wu ZP, Eitan S, Ivkovic S, Lu Y, Dang H, Middleton B, Bilousova TV, Yoshimura Y, Evans CJ, Joyce S, Tian J and Kaufman DL. Neurons preferentially respond to self-MHC class I allele products regardless of peptide presented. J Immunol. 2010; 184: 816-23.

Hoek KL, LE Gordy, PL Collins, VV Parekh, TM Aune, S Joyce, JW Thomas, L Van Kaer and Eric Sebzda. Follicular B cell trafficking within the spleen actively restricts humoral immune responses. Immunity. 2010; 33: 254-65.

Van Kaer L and S Joyce. The hunt for iNKT cell antigens: α-galactosidase-deficient mice to the rescue? [editorial]. Immunity. 2010; 33: 143-5.

Florence WC, Xia C, Gordy LE, Chen W, Zhang Y, Scott-Browne J, Kinjo Y, Yu KO, Keshipeddy S, Pellicci DG, Patel O, Kjer-Nielsen L, McCluskey J, Godfrey DI, Rossjohn J, Richardson SK, Porcelli SA, Howell AR, Hayakawa K, Gapin L, Zajonc DM, Wang PG, Joyce S. Adaptability of the semi-invariant natural killer T-cell receptor towards structurally diverse CD1d-restricted ligands. EMBO J. 2009 Dec 12/2/2009; 28(23): 3781. PMID: 19953109, PMCID: PMC2790496, PII: emboj2009348, DOI: 10.1038/emboj.2009.348, ISSN: 1460-2075.

WC Florence, C Xia, LE Gordy, W Chen, Y Zhang, J Scott-Browne, Y Kinjo, KOA Yu, S Keshipeddy, DG Pellicci, O Patel, L Kjer-Nielsen, J McCluskey, DI Godfrey, J Rossjohn, SK Richardson, SA Porcelli, AR Howell, K Hayakawa, L Gapin, DM Zajonc, PG Wang and S Joyce. Adaptability of the semi-invariant natural killer T-cell receptor towards structurally diverse CD1d-restricted ligands. EMBO J. 2009; 28: 3579-90.

Ni CY, Wu ZH, Florence WC, Parekh VV, Arrate MP, Pierce S, Schweitzer B, Van Kaer L, Joyce S, Miyamoto S, Ballard DW, Oltz EM. Cutting edge: K63-linked polyubiquitination of NEMO modulates TLR signaling and inflammation in vivo. J. Immunol. 2008 Jun 6/1/2008; 180(11): 7107-11. PMID: 18490708, PMCID: PMC2601684, PII: 180/11/7107, ISSN: 0022-1767.

Joyce S, Van Kaer L. Invariant natural killer T cells trigger adaptive lymphocytes to churn up bile. Cell Host Microbe. 2008 May 5/15/2008; 3(5): 275-7. PMID: 18474352, PII: S1931-3128(08)00125-X, DOI: 10.1016/j.chom.2008.04.007, ISSN: 1934-6069.

Florence WC, Bhat RK, Joyce S. CD1d-restricted glycolipid antigens: presentation principles, recognition logic and functional consequences. Expert Rev Mol Med. 2008; 10: e20. PMID: 18601810, PII: S1462399408000732, DOI: 10.1017/S1462399408000732, ISSN: 1462-3994.

Joyce, S. and Van Kaer, L. Lung NKT cell commotion takes your breath away [editorial]. Nature Med. 2008; 14: 609-10.

Villarino AV, Artis D, Bezbradica JS, Miller O, Saris CJ, Joyce S and Hunter CA. IL-27R deficiency delays the onset of colitis and protects from helminth-induced pathology in a model of chronic IBD. Int Immunol. 2008; 20: 739-52.

Torres, V.J., Stauff, D.L., Pishchany, G., Bezbradica, J.S., Gordy, L.E., Iturregui, J., Anderson, K.L., Dunman, P.M., Joyce, S. and Skaar. A Staphylococcus aureus regulatory system that responds to host heme and modulates virulence. Cell Host Microbe. 2007; 1: 109-19.

Bezbradica JS, Van Kaer L and Joyce S. A20180: Natural killer T cells. Encyclopaedia of Life Sciences. 2007; A20180: DOI: 10.1002/9780470015902.a0020180.

Bezbradica JS, Stanic AK, Joyce S. Characterization and functional analysis of mouse invariant natural T (iNKT) cells. Curr Protoc Immunol. 2006 Jul; Chapter 14: Unit 14.13. PMID: 18432968, DOI: 10.1002/0471142735.im1413s73, ISSN: 1934-368X.

Major AS, Joyce S, Van Kaer L. Lipid metabolism, atherogenesis and CD1-restricted antigen presentation. Trends Mol Med [print-electronic]. 2006 Jun; 12(6): 270-8. PMID: 16651026, PII: S1471-4914(06)00071-2, DOI: 10.1016/j.molmed.2006.04.004, ISSN: 1471-4914.

Yan J, Parekh VV, Mendez-Fernandez Y, Olivares-Villagómez D, Dragovic S, Hill T, Roopenian DC, Joyce S, Van Kaer L. In vivo role of ER-associated peptidase activity in tailoring peptides for presentation by MHC class Ia and class Ib molecules. J. Exp. Med [print-electronic]. 2006 Mar 3/20/2006; 203(3): 647-59. PMID: 16505142, PMCID: PMC2118255, PII: jem.20052271, DOI: 10.1084/jem.20052271, ISSN: 0022-1007.

Major AS, Singh RR, Joyce S, Van Kaer L. The role of invariant natural killer T cells in lupus and atherogenesis. Immunol. Res. 2006; 34(1): 49-66. PMID: 16720898, PMCID: PMC2291524, PII: IR:34:1:49, ISSN: 0257-277X.

Van Kaer, L. and Joyce, S. Viral evasion of antigen presentation: not just for peptides anymore. Nature Immunol. 2006; 7: 795-7.

Bezbradica, J.S., Gordy, L.E., Stanic, A.K., Dragovic, S., Hill, T., Hawiger, J., Unutmaz, D., Van Kaer, L. and Joyce, S. Granulocyte-macrophage colony-stimulating factor regulates effector differentiation of invariant natural killer T cells during thymic ontogeny. Immunity. 2006; 25: 487-97.

Bezbradica, J.S., Hill, T., Stanic, A.K., Van Kaer, L. and Joyce, S. Commitment toward the natural T (iNKT) cell lineage occurs at the CD4+8+ stage of thymic ontogeny. Proc. Natl. Acad. Sci. USA. 2005; 102: 5114-9.

Bezbradica, J.S., Stanic, A.K., Matsuki, N., Bour-jordan, H., Bluestone, J.A., Thomas, J.W., Unutmaz, D., Van Kaer, L. and Joyce, S.. Distinct roles of dendritic cells and B cells in Va14Ja18 natural T cell activation in vivo. J. Immunol. 2005; 174: 4696-705.

Van Kaer, L. and Joyce, S.. Innate Immunity: NKT cells in the spotlight [editorial]. Current Biology. 2005; 15: R429-R431.

Singh, A.K., Yang, J.-Q., Parekh, V.V., Wei, J., Wang, C.-R., Joyce, S., Singh, R.R. and Van Kaer, R.. The natural killer T cell ligand alpha-galactosylceramide prevents or promotes pristane-induced lupus in mice. Eur. J. Immunol. 2005; 35: 1143-54.

Parekh, V.V., Wilson, M.T., Olivares-Villagomez, D., Singh, A.K., Wu, L., Wang, C.-R., Joyce, S. and Van Kaer, L.. Glycolipid antigen induces long-term natural killer T cell anergy in mice. J. Clin. Invest. 2005; 115: 2572-83.

Bezbradica, J.S. and Joyce, S. In R. Gorczynski Ed. Altered Immunoregulation and Human Disease. [place unknown: publisher unknown]; 2005.

Major AS, Wilson MT, McCaleb JL, Ru Su Y, Stanic AK, Joyce S, Van Kaer L, Fazio S, Linton MF. Quantitative and qualitative differences in proatherogenic NKT cells in apolipoprotein E-deficient mice. Arterioscler. Thromb. Vasc. Biol [print-electronic]. 2004 Dec; 24(12): 2351-7. PMID: 15472130, PII: 01.ATV.0000147112.84168.87, DOI: 10.1161/01.ATV.0000147112.84168.87, ISSN: 1524-4636.

Yoshimura, Y., Yadav, R., Christainson, G.J., Ajayi, W.U., Roopenian, D.C. and Joyce, S. Duration of alloantigen presentation and the avidity of T cell antigen recognition correlate with immunodominance of CTL response to minor histocomptibility antigens. J. Immunol. 2004; 172: 6666-74.

Park, J.-J., Kang, S.-J., De Silva, A.D., Stanic, A.K., Casorati, G., Hachey, D.L., Cresswell, P. and Joyce, S. Lipid-protein interactions: Biosynthetic assembly of CD1 with lipids in the endoplasmic reticulum is evolutionarily conserved. Proc. Natl. Acad. Sci. USA. 2004; 101: 1022-6.

Stanic, A.K., Bezbradica, J.S., Park, J.-J., Matsuki, N., Mora, A.L., Van Kaer, L., Boothby, M. and Joyce, S. NF-kB controls cell fate specification, survival, and molecular differentiation of immunoregulatory natural T lymphocytes. J. Immunol. 2004; 172: 2265-73.

Stanic, A.K., Bezbradica, J.S., Park, J.-J., Van Kaer, L., Boothby, M. and Joyce, S. The ontogeny and function of Va14Ja18 natural T lymphocytes require signal processing by protein kinase C-theta and NF-kB. J. Immunol. Cutting Edge. 2004; 172: 4667-71.

Parekh, V.V., Singh, A.K., Wilson, M.T., Olivares-Villagomez, D., Bezbradica, J,S., Inazawa, H., Ehara, H., Sakai, T., Serizawa, I., Wu, L., Wang, C.-R., Joyce, S. and Van Kaer, L.. Quantitative and qualitative differences in the in vivo response of NKT cells to distinct alpha- and beta-anomeric glycolipids. J. Immunol. 2004; 173: 3693-706.

Zhang F, Liang Z, Matsuki N, Van Kaer L, Joyce S, Wakeland EK, Aune TM. A murine locus on chromosome 18 controls NKT cell homeostasis and Th cell differentiation. J. Immunol. 2003 Nov 11/1/2003; 171(9): 4613-20. PMID: 14568935, ISSN: 0022-1767.

Joyce S, Van Kaer L. CD1-restricted antigen presentation: an oily matter. Curr. Opin. Immunol. 2003 Feb; 15(1): 95-104. PMID: 12495740, PII: S0952791502000122, ISSN: 0952-7915.

Stanic, A.K., De Silva, A.D., Park, J.-J. Sriram, V., Ichikawa, M., Hirabayashi, Y., Van Kaer, L., Brutkiewicz, R.R., and Joyce, S. Defective presentation of the CD1d1-restricted natural Va14Ja18 NKT lymphocyte antigen caused by b-D-glucosylceramide synthase deficiency. Proc. Natl. Acad. Sci. USA. 2003; 100: 1849-54.

Yang, L., Yamagata, N., Yadav, R., Brandon, S. Courtney, R.L., Marrow, J.D. Shyr, Y., Boothby, M., Joyce, S., Carbone, D.P. and Breyer, R.M. Cancer-associated immunodeficiency and dendritic cell abnormalities mediated by the prostaglandin EP2 receptor. J. Clin. Invest. 2003; 111: 727-35.

Chun, T., Page, M.J., Gapin, L., Matsuda, J.L., Xu, H., Nguyen, H., Kang, H.S., Stanic, A.K., Joyce, S., Chorney, M.J., Kronenberg, M. and Wang, C.-R. CD1d-espressing dendritic cells but not thymic epithelial cells can mediate negative selection of NKT cells. J. Exp. Med. 2003; 197: 907-18.

Yadav, R., Yoshimura, Y., Boesteanu, A., Christianson, G.J., Ajayi, W.U., Shashidharamurthy, R., Stanic, A.K., Roopenian, D.C. and Joyce, S. The H4b minor histocompatibility antigen is caused by a combination of genetically determined and posttranslational modifications. J. Immunol. 2003; 170: 5133-42.

Matsuki, N., Stanic, A.K., Embers, M.E., Van Kaer, L., Morel, L. and Joyce, S. Genetic dissection of Va14Ja18 natural T cell number and function in autoimmune-prone mice. J. Immunol. 2003; 170: 5429-37.

Stanic, A.K., Park, J.-J. and Joyce, S. Innate self recognition by an invariant, rearranged T-cell receptor and its immune consequences. Immunology. 2003; 171-84.

Wilson, M.T., Johansson, C., Olivares-Villagómez, D., Singh, A.K., Stanic, A.K., Wang, C.-R., Joyce, S., Wick, M.J. and Van Kaer, L. The response of natural killer T cells to glycolipid antigens is characterized by surface receptor down-modulation and expansion. Proc. Natl. Acad. Sci. USA. 2003; 100: 10919-24.

Motsinger, A., Azimzadeh, A., Stanic, A.K., Johnson, R.P., Van Kaer, L., Joyce, S. and Unutmaz, D. Identification and simian immunodeficiency virus infection of CD1d-restricted macaque natural killer T cells. J. Virol. 2003; 77: 8153-8.

Stanic, A.K., Shashidharamurthy, R., Bezbradica, J.S., Matsuki, N., Yoshimura, Y., Miyake, S., Choi, E.Y., Schell, T.D., Van Kaer, L., Tevethia, S.S., Roopenian, D.C., Yamamura, T. and Joyce, S.. Another view of T cell antigen recognition: Cooperative engagement of glycolipid antigens by Va14Ja18 natural T cell receptor. J. Immunol. 2003; 171: 4539-51.

Mora, A.L., Corn, R.A., Stanic, A.K., Goenka, S., Aronica, M., Stanley, S., Ballard, D.W., Joyce, S. and Boothby, M. Antiapoptotic function of NF-kB in T lymphocytes is influenced by their differentiation status: roles of Fas, c-FLIP, and Bcl-xL. Cell Death Differentiation. 2003; 10: 1032-44.

Yang, J., Jaramillo, A., Liu, W., Olack, B., Yoshimura, Y., Joyce, S., Kaleem, Z., Mohanakumar, T. Chronic rejection of murine cardiac allografts discordant at the H13 minor histocompatibility antigen correlates with the generation of the H13-specific CD8+ cytotoxic T cells. Transplantation. 2003; 76: 84-91.

Yang, J.-Q., Singh, A.K., Wilson, M.T., Satoh, M., Stanic, A.K., Park, J.-J., Hong, S., Gadola, S.D., Mizutani, A., Kakumanu, S.R., Reeves, W.H., Cerundolo, V., Joyce, S., Van Kaer, L., and Singh, R.R. Immunoregulatory role of CD1d in the hydrocarbon oil-induced model of lupus nephritis. J. Immunol. 2003; 171: 2142-53.

Choi, E.Y., Christianson, G.J., Yoshimura, Y., Jung, N., Sporule, T.J., Malarkannan, S., Joyce, S. and Roopenian, D.C. Real time profiling identifies H60 as a major minor histocompatibility antigen in murine graft-versus-host disease. Blood. 2002; 100: 4259-65.

Choi , E.Y, Christianson, G.J., Yoshimura, Y., Sproule, T.J., Jung, N., Joyce, S., and Roopenian, D.C. Immunodominance of H60 is caused by an abnormally high precursor T cell pool directed against its unique minor distocompatibility antigen peptide. Immunity. 2002; 17: 593-603.

Kennedy, M.K., Glacuum, M., Brown, S.N., Butz, E.A., Embers, M.E., Matsuki, N., Charrier, K., Sedger, L., Brasel, K., Morrissey, P.J., Stocking, K., Schuh, J.C.L., Joyce, S. and Peschon, J.J. Reversible defects in natural killer and memory CD8 T cell lineages in IL-15 deficient mice. 2000.

De Silva, A.D., Boesteanu, A., Song, R., Harhaj, E., Harding, C.V. and Joyce, S. Thermolabile H-2Kb molecules expressed by transporters associated with antigen processing-deficient RMA-S cells are occupied by low affinity peptides. 1999.

Goyarts, E.C., Vegh, Z., Kalergis, A.M., Horig, H., Papadopolous, N.J., Young, A.C.M., Thomson, C.T., Chang, H.-C., Joyce, S. and Nathenson, S.G. Point mutations in the b-chain CDR3 can alter the T cell receptor recognition pattern on an MHC class I/peptide complex over a broad interface area. 1998.

Boesteanu, A., Brehm, M., Mylin, L.M., Christionson, G,J., Tevethia, S.S., Roopenian, D.C. and Joyce, S. A molecular basis for how a single T cell receptor interfaces multiple ligands. 1998.

Joyce, S., Woods, A.S., Yewdell, J.W., Bennink, J.R., De Silva, A.D., Boesteanu, A., Balk, S.P., Cotter, R.J. and Brutkiewicz, R.R. A natural ligand of mouse CD1d1: cellular glycosylphosphatidylinositol. 1998.

Boesteanu, A., De Silva, A.D., Nakajima, H., Leonard, W.J., Peschon, J.J. and Joyce, S. Distinct roles for signals relayed through the common cytokine receptor g-chain and interleukin-7 receptor a-chain in natural T cell development. 1997.

Mendiratta S, Martin, DW, Hong S, Boesteanu A, Joyce S and Van Kaer L. CD1d1 mutant mice are deficient in natural T cells that promptly produce IL-4. 1997.

Joyce S. Traffic control of completely assembled MHC class I molecules beyond the endoplasmic reticulum. 1997.

Joyce S, Nathenson SG. Alloreactivity, antigen recognition and T-cell selection: three diverse T-cell recognition problems with a common solution. Immunol. Rev. 1996 Dec; 154: 59-103. PMID: 9034864, ISSN: 0105-2896.

Joyce S, Negishi I, Boesteanu A, DeSilva AD, Sharma P, Chorney MJ, Loh DY, Van Kaer L. Expansion of natural (NK1+) T cells that express alpha beta T cell receptors in transporters associated with antigen presentation-1 null and thymus leukemia antigen positive mice. J. Exp. Med. 1996 Oct 10/1/1996; 184(4): 1579-84. PMID: 8879233, PMCID: PMC2192848, ISSN: 0022-1007.

Sharma P, Joyce S, Chorney KA, Griffith JW, Bonneau RH, Wilson FD, Johnson CA, Flavell RA, Chorney MJ. Thymus-leukemia antigen interacts with T cells and self-peptides. J. Immunol. 1996 Feb 2/1/1996; 156(3): 987-96. PMID: 8558026, ISSN: 0022-1767.

Joyce S, Kuzushima K, Kepecs G, Angeletti RH, Nathenson SG. Characterization of an incompletely assembled major histocompatibility class I molecule (H-2Kb) associated with unusually long peptides: implications for antigen processing and presentation. Proc. Natl. Acad. Sci. U.S.A. 1994 May 5/10/1994; 91(10): 4145-9. PMID: 8183884, PMCID: PMC43741, ISSN: 0027-8424.

Joyce S, Tabaczewski P, Angeletti RH, Nathenson SG, Stroynowski I. A nonpolymorphic major histocompatibility complex class Ib molecule binds a large array of diverse self-peptides. J. Exp. Med. 1994 Feb 2/1/1994; 179(2): 579-88. PMID: 8294869, PMCID: PMC2191392, ISSN: 0022-1007.

Joyce S, Nathenson SG. Methods to study peptides associated with MHC class I molecules. Curr. Opin. Immunol. 1994 Feb; 6(1): 24-31. PMID: 7513524, ISSN: 0952-7915.

Joyce S, Sun R, Nathenson SG. Mapping the orientation of an antigenic peptide bound in the antigen binding groove of H-2Kb using a monoclonal antibody. Biochem. Biophys. Res. Commun. 1992 Aug 8/14/1992; 186(3): 1449-54. PMID: 1380802, PII: S0006-291X(05)81569-4, ISSN: 0006-291X.

Joyce S, Mathew JM, Flye MW, Mohanakumar T. A polymorphic human kidney-specific non-MHC alloantigen. Its possible role in tissue-specific allograft immunity. Transplantation. 1992 May; 53(5): 1119-27. PMID: 1374945, ISSN: 0041-1337.

Shibata K, Imarai M, van Bleek GM, Joyce S, Nathenson SG. Vesicular stomatitis virus antigenic octapeptide N52-59 is anchored into the groove of the H-2Kb molecule by the side chains of three amino acids and the main-chain atoms of the amino terminus. Proc. Natl. Acad. Sci. U.S.A. 1992 Apr 4/1/1992; 89(7): 3135-9. PMID: 1313583, PMCID: PMC48819, ISSN: 0027-8424.

Mathew JM, Joyce S, Lawrence W, Mohanakumar T. Evidence that antibodies eluted from rejected kidneys of HLA-identical transplants define a non-MHC alloantigen expressed on human kidneys. Transplantation. 1991 Sep; 52(3): 559-62. PMID: 1897033, ISSN: 0041-1337.

Joyce S, Flye MW, Mohanakumar T. Human kidney specific non-MHC antigen: isolation and characterization using eluates from rejected renal allografts. Transplant. Proc. 1989 Feb; 21(1 Pt 1): 628-9. PMID: 2650207, ISSN: 0041-1345.

Joyce S, Flye MW, Mohanakumar T. Characterization of kidney cell-specific, non-major histocompatibility complex alloantigen using antibodies eluted from rejected human renal allografts. Transplantation. 1988 Sep; 46(3): 362-9. PMID: 3047925, ISSN: 0041-1337.

Sood PP, Joyce S, Unnikumar KR. Histoenzymological compartmentation of the embryonic shrew tooth. J Oral Med. 1984 Oct; 39(4): 250-3. PMID: 6094772, ISSN: 0022-3247.

Available Postdoctoral Position Details
Posted: 11/23/2021

For details visit us at: www.vumc.org/joyce-lab/

Seeking an outstanding individual for a fully funded (NIH, VA Merit) postdoctoral position in Immunology. Current projects include,

(1) T cell dependent protective vaccine design and mechanism/s (see Scientific Rep 10: 13167, 2020: https://doi.org/10.1038/s41598-020-69897-w; ACS Nano 14: 9904—9916, 2020: https://pubs.acs.org/doi/10.1021/acsnano.0c02765; ACS Nano 13: 10939—10960, 2019; https://pubs.acs.org/doi/10.1021/acsnano.9b00326; Cell Reports 16: 1800—1809, 2016: https://doi.org/10.1016/j.celrep.2016.07.037)

(2) the role of innate T lymphocytes in infection and immunity (see PLoS Pathog. 11: e1004975, 2015: https://doi.org/10.1371/journal.ppat.1004975)

(3) the developmental and evolutionary (devo-evo) biology of innate T lymphocytes (see Proc. Natl. Acad. Sci. USA 117: 17156—17165, 2020: https://doi.org/10.1073/pnas.2001665117; Frontiers Immunol. 8:1858, 2017: https://doi.org/10.3389/fimmu.2017.01858)

(4) the control of bacterial and viral protein antigen transport from the cytoplasm of infected cells to sites of MHC-I and MCH-II restricted antigen presentation.

Multi-disciplinary approaches will include, immunologic, cell and molecular biologic, biochemical, proteomics and genomics, to gain mechanistic insights. New knowledge gained from the four projects have implications for augmenting immunity through vaccine design to prevent or to treat infectious diseases and cancers as well as understanding inflammatory diseases such as graft-versus-host disease and autoimmunity.

Qualified candidates should send their application with a cover letter stating research interests and career goals, full CV, and contact information for three references directly to

Sebastian Joyce: < sebastian.joyce@vumc.org >.

Salary commensurate with experience