- 2010 - Melville A. Hare Award for Distinction in Research
Ana Goyos was born in Hialeah, Florida on March 17, 1977. She attended Florida International University from 1998 to 2003, and graduated with a Bachelor of Science degree in 2003. She came to the University of Rochester in the summer of 2004 and began her graduate studies in Immunology. She received a Provost Fellowship from the University of Rochester in 2004 and she also received a NIH Pre-doctoral Fellowship in 2005. She pursued her research in the study of nonclassical MHC class Ib evolution and immune functions in Xenopus laevis and Silurana tropicalis under the direction of Professor Jacques Robert and received the Master of Science degree from the University of Rochester in 2006.
Major histocompatibility complex (MHC) class Ia (class Ia) are evolutionary conserved genes in jawed vertebrates encoding highly polymorphic and ubiquitously expressed surface molecules essential for the development and activation of CD8 T cells. By contrast, nonclassical MHC class Ib (class Ib) are a group of heterogeneous genes encoding molecules structurally similar to class Ia but with a more limited tissue distribution and polymorphism. In mammals, class Ibs have diverse, and often not well characterized, functions that include stress responses, detection of malignancy, immune regulation and the differentiation of CD8 T cells. Although class Ib genes have been identified in all taxa of jawed vertebrates, information about their function is even more limited and their phylogeny is uncertain. This is usually attributed to their fast rate of evolution.
The subfamily Xenopodinae, including species of the clawed frog genera Xenopus and Silurana, which diverged from a common ancestor 80 million years ago (MYA), provides a powerful non-mammalian model to further investigate the evolution and immune functions of class Ib genes. Xenopus laevis is one of the best characterized and most widely used non-mammalian animal models to study immunity. We used this species to investigate the role of class Ib in early T cell ontogeny and in tumor immunity. The genome of the diploid Silurana tropicalis has been fully sequenced and annotated. We used this species to evaluate the genomic and molecular evolution of class Ib genes.
Genomic, molecular and phylogenetic studies reveal an unexpected degree of conservation (9 out of 13 class Ib subfamilies are homologous between X. laevis and S. tropicalis) of class Ib genes in Xenopodinae throughout a period of time (80 MY) similar to that which separates primates and rodents from a common ancestor. This study also unveils the ancient origin and uniqueness of one X. laevis class Ib gene, XNC10, which has an unequivocal ortholog in S. tropicalis, SNC10. XNC10 is preferentially expressed by CD8 thymocytes and by a subset of peripheral effector CD8 T cells in adults. In larvae, XNC10 is expressed from the onset of thymus organogenesis during which no class Ia protein expression is detected. These data strongly suggest that XNC10 is involved in T cell ontogeny.
To investigate how conserved the involvement of class Ib gene products are in tumor immunity, we took advantage of a X. laevis transplantable lymphoid tumor cell line (15/0) that is class Ia deficient, and whose killing involves unconventional CD8 cytotoxic T cells that are antigen-specific and class Ia-unrestricted (CCU-CTL). We generated, for the first time in ectothermic vertebrates, stable tumor transfectants expressing shRNA effectively silencing either β2-microglobulin, to prevent class Ib surface expression, or class Ib directly. Both types of 15/0 tumor transfectants are more resistant to CCU-CTL killing and more tumorigenic, while more susceptible to NK-like cell killing. These data are consistent with a conserved role of class Ib molecules in regulating anti-tumor NK and CD8 T cell responses.
Overall, this study highlights the unusual evolutionary conservation of class Ib genes in Xenopodinae, and their involvement in tumor immunity and in the development of CD8 T cells. Finally, this work gives a foundation for Xenopodinae to serve as a useful comparative non-mammalian model system to decipher the evolution and function of class Ib genes in immunity.
- Chida S., Goyos, A. and Robert J. (2011). Phylogeny and developmental expression of CD8alpha, beta and CD4 genes in the amphibian Xenopus Dev. Comp. Immunol. 35(3): 366-377.
- Goyos A, Sowa J, Ohta Y, Robert J. (2011). Remarkable conservation of distinct nonclassical MHC class Ib gene lineages in divergent amphibian species. J. Immunol 186:372-381.
- Goyos A, Ohta Y, Guselnikov S. and Robert J. (2009). Novel nonclassical MHC class Ib genes associated with CD8 T cell development and thymic tumors. Mol Immunol. 46(8-9):1775-1786.
- Goyos A, Guselnikov S, Chida AS, Sniderhan LF, Maggirwar SB, Nedelkovska H, Robert J. (2007). Involvement of nonclassical MHC class Ib molecules in heat shock protein-mediated anti-tumor responses. Eur J Immunol. 37(6):1494-1501.
- Marr S, Goyos A, Gantress J, Maniero GD, Robert J. (2005). CD91 up-regulates upon immune stimulation in Xenopus adult but not larval peritoneal leukocytes. Immunogenetics. 56(10): 735-42.
- Goyos A, Cohen N, Gantress J, Robert J. (2004). Anti-tumor MHC class Ia-unrestricted CD8 T cell cytotoxicity elicited by the heat shock protein gp96. Eur J Immunol. 34(9): 2449-58.
- Robert, J., Cohen, N., Goyos, A., Maniero, G., Morales, H., and Gantress, J. (2003). Immunomodulation by the heat shock protein gp96. In: Immunoproteins and novel mechanisms of immuoregulation. (ed., J. Marchalonis). Cellular Mol. Biol. 49:263-275.
- Goyos, A. and Robert J. (2009). Tumorigenesis and anti-tumor immune responses in Xenopus laevis. In The frog Xenopus as a model to study evolutionary, developmental and biomedical immunology. Frontiers in Bioscience. Ed. J. Robert. 14:167-176.
- Robert J, Goyos A and Nedelkovska H. (2009). Xenopus, a unique comparative model to explore the role of certain heat shock proteins and non-classical MHC class Ib gene products in immune surveillance. Immunol Res. 45:114-122