Biography:

Dr. Yuhki obtained his Ph.D. and D.D.S. degrees from Hokkaido University in Japan. He studied cellular and molecular biological aspects of differentiating myelomonocytic leukemia cells with professor Hiroshi Kobayashi at Hokkaido University , School of Medicine . He performed his postdoctoral work on major histocompatibility complex genes with Stephen J. O'Brien in the LGD. He is Senior Staff Scientist, LGD, CCR, NCI , National Institutes of Health and Head of Sequencing Core Facility in LGD and responsible for operations of sequencing and genotyping using Biomek Fx automated laboratory workstation and ABI 3730XL automated DNA analyzer.

Research:

1) Molecular Biology/Computational Biology/Comparative Genomics/Epigenetics/ Immunology

2) Comparative Genome Research of Immune System(s) and Resistant Mechanism(s) against Emerging Infectious Diseases

In the 20 th century, two major human pandemics have occurred by interspecies transmission of pathogens. Approximately 100 million people have succumbed to 1918 Spain influenza virus, which is caused by mutation and transmission of avian flu virus to human. More than 55 million people have been infected to human AIDS virus, which is believed to be transmitted from chimpanzee to human in the early 20 th century and spread out to all over the world since early 1980 th . In recent years, it became more evident that many pathogens in natural hosts can cause emerging diseases in human (i.e. Ebola hemorrhagic fever, severe acute respiratory syndrome (SARS), potential future pandemic of human influenza through mutations and transmission of avian flu H5N1). LGD maintains and organizes extensive collections of tissue, blood, and skin samples of mammals, marsupials, which give important opportunities to study many pathogens to identify pathogens and prevent future pandemics of our species. Particularly, LGD maintains a full set of 37 feline species samples, including more than 13,000 individuals and 3762 DNA samples. Moreover, more than 1,000 feline immunodeficiency virus (FIV) positive samples were identified either ELISA/western blotting by serum or PCR methods. Of these 1000 samples, more than 80 percent of FIV positive cases were detected from African lion and puma samples, in most cases, without obvious onsets of AIDS. Based on those backgrounds, LGD has initiated four major projects to study emerging infectious diseases.

• Geophylogenetic characterization of FIV
• Comparative viral genome characterization of FIV of domestic cat (AIDS-competent) and lion/puma (AIDS-incompetent)
• Host-virus interaction
• Screening emerging pathogens

My research focuses on specially two major projects, host-virus interation and screening emerging pathogens. (click to read more research details)

Publications:

Yuhki, N. and O'Brien, S.J.: DNA variation of the mammalian major histocompatibility complex reflects genomic diversity and population history. Proc. Natl. Acad. Sci. USA 87: 836 840, 1990. [ PDF ]

Yuhki, N. and O'Brien, S.J.: DNA recombination and natural selection pressure sustains genetic sequence diversity of the feline MHC class I genes. J. Exp. Med. 172: 621 630, 1990.

Yuhki, N. and O'Brien, S.J.: Exchanges of short polymorphic DNA segments predating speciation in feline major histocompatibility complex class I genes. J. Mol. Evol. 39: 22 33, 1994.

Brown, E.W., Yuhki, N., Packer, C. and O'Brien, S.J.: A lion lentivirus (LLV) related to feline immunodeficiency virus: Epidemiologic and phylogenetic aspects. J. Virol. 68: 5953 5968, 1994. [ PDF ]

Yuhki, N. and O'Brien, S.J.: Nature and origin of polymorphism in feline major histocompatibility complex (MHC) class II DRA and DRB genes. J. Immunol. 158: 2822 2833, 1997. [ PDF ]

Yuhki, N., Beck, T., Stephens, R.M., Nishigaki, Y., Newmann, Y. and O'Brien, S.J.: Comparative genome organization of human, murine and feline major histocompatibility complex class II region. Genome Res. 13: 1169-79, 2003.

Beck, T., Menninger, J., Murphy, W.J., Nash, W.G., O’Brien, S.J., and Yuhki, N.: The Feline Major Histocompatibility Complex Is Rearranged by Inversion with a Breakpoint in the Distal Class I Region. Immunogenet. 56: 702-709, 2005. [ PDF ]

Muenk C, Zielonka J, Hotz-Wagenblatt A, Chareza S, Battenberg M, Thielebein J, Cichutek K, Bravo I, O'Brien S, Loechelt M, Yuhki N:  Functions, structure, and read-through alternative splicing of feline APOBEC3 genes.  Genome Biology. 9:R48, 2008.

Pontius JU, Mullikin JC, Smith DR, Lindblad-Toh K, Gnerre S, Clamp M, Chang J, Stephens R, Neelam B, Volfovsky N, Schaffer AA, Agarwala R, Narfstram K, Murphy WJ, Giger U, Roca AL, Antunes A, Menotti-Raymond M, Yuhki N, Pecon-Slattery J, Johnson WE, Bourque G, Tesler G, O'Brien SJ:  Initial sequence and comparative analysis of the cat genome.  Genome Res. 17:1675-89, 2007.  [PDF]

Fyfe JC, Kurzhals RL, Hawkins MG, Wang P, Yuhki N, Giger U, Van Winkle TJ, Haskins ME, Patterson DF, Henthorn PS:  A complex rearrangement in GBE1 causes both perinatal hypoglycemic collapse and late-juvenile-onset neuromuscular degeneration in glycogen storage disease type IV of Norwegian forest cats.  Mol. Genet. Metab. 90:383-92, 2007.  [PDF]