My current research interests are the search for the origins of immune genes and the manner by which the immune system was shaped over evolutionary time. Over the past few years, researchers have isolated immune genes from many vertebrate and invertebrate species and compared them to their well-known mammalian counterparts. Thus far, the non-specific "innate" immune system is found in all living organisms, whereas the antigen-specific "adaptive" immune system is only found in jawed vertebrates. There are three major molecules that define the adaptive immune system: 1) immunoglobulin (antibody), 2) the major histocompatibility complex (MHC) (antigen processing and presentation), and 3) T cell receptor (recognize antigen and initiate cellular immune system). My research focuses on the MHC in sharks and frogs. In the search for the primordial MHC genes and to understand the primordial MHC gene organization we use computational bioinformatics as well as hands-on bench work such as cloning and mapping. MHC also provides good evidence of "the 2R hypothesis"; two rounds of ancient genome-wide (or large genome region) duplications which shaped the modern vertebrate genome. Human and mouse genome sequences have revealed that there are three other (paralogous) regions containing MHC homologous genes linked in a similar order. However, as the most recent duplication happened many millions years ago in our ancestor, linkage conservation is not obvious in some regions. In contrast, polyploid frog species in the genus Xenopus arose by genome-wide duplication more recently, providing us with a vertebrate model to examine the fate of duplicated genomic regions. Other projects currently underway or planned include a study on the transcriptional regulation of MHC genes, identifying the different expression pattern among immune genes before and after Xenopus metamorphose using microarray analysis, chromosomal distribution of immune genes, and identifying new types of immune related genes.
Luo M, Kim H, Kudrna D, Sisneros NB, Lee SJ, Mueller C, Collura K, Zuccolo A, Buckingham EB, Grim SM, Yanagiya K, Inoko H, Shiina T, Flajnik MF, Wing RA, Ohta Y. 2006. Construction of a nurse shark (Ginglymostoma cirratum) bacterial artificial chromosome (BAC) library and a preliminary genome survey.BMC Genomics 7:106
Ohta Y. and Flajnik M. 2006. IgD, like IgM, is a primordial immunoglobulin class perpetuated in most jawed vertebrates.Proc Natl Acad Sci U S A 103: 10723-10728.
Ohta Y, Goetz W, Hossain MZ, Nonaka M, Flajnik MF. 2006. Ancestral organization of the MHC revealed in the amphibian Xenopus.J Immunol 176:3674-85.
Rebecca Stewart, Yuko Ohta, Ralph R. Minter, Terry Gibbons, Trudy L. Horton, Pamela Ritchie, John D. Horton, Martin F. Flajnik, and Martin D. Watson. 2005. Cloning and characterization of Xenopus β2-microglobulin. Dev. Comp. Immunol. 29(8):723-32.
Ohta Y, Landis E, Boulay T, Phillips RB, Collet B, Secombes CJ, Flajnik MF, Hansen JD. 2004. Homologs of CD83 from elasmobranch and teleost fish. J Immunol. 173(7):4553-60.
Yuko Ohta, Rebecca Lohr, Simon Powis, Masaru Nonaka, Louis du Pasquier, and Martin Flajnik. 2003. Two ancient allelic lineages of Transporter Associated with Antigen Processing Gene (TAP1) in Xenopus: The evidence of co-evolution between transporter genes, LMP7 and class I in Xenopus MHC. Eur J Immunol. 33(11):3017-27.
Terado T, Okamura K, Ohta Y, Shin DH, Smith SL, Hashimoto K, Takemoto T, Nonaka MI, Kimura H, Flajnik MF, and Nonaka M. 2003. Molecular cloning of C4 gene and identification of the class III complement region in the shark MHC. J. Immunol. 171(5):2461-2466.
Takeo Nagata, Takashi Suzuki, Yuko Ohta, Martin F. Flajnik, and Masanori Kasahara. 2002. The leukocyte common antigen (CD45) of the Pacific hagfish, Eptatretus stoutii: Implication for the primordial function of CD45. Immunogenetics 54(4):286-91.
Susan S. Lee, Daniel Tranchina, Yuko Ohta, Martin F. Flajnik, and Ellen Hsu. 2002. Hypermutation in Shark Immunoglobulin Light Chain Genes Results in Contiguous Substitutions. Immunity 16(4):571-582.
Yuko Ohta, Churchill McKinney, and Martin Flajnik. 2002. Proteasome,TAP, and class I genes in the nurse shark Ginglymostoma cirratum: evidence for a stable "class I region" and MHC haplotype lineages. J Immunol. 168:771-781.
Flajnik MF, and Ohta Y. 2000. Major histocompatibility complex: Evolution, structure, and function. Kasahara M ed. Springer, pp248-259.
Ohta Y, Okamura K, McKinney EC, Bartl S, Hashimoto K, and Flajnik MF. 2000. Primitive synteny of vertebrate major histocompatibility complex class I and class II genes. Proc. Natl. Acad. Sci. 97(9):4712-4717.
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