Masahiro Yamashita, PhD

  • Assistant Professor of Medical Sciences (in Medicine) at CUMC
Profile Headshot

Overview

Academic Appointments

  • Assistant Professor of Medical Sciences (in Medicine) at CUMC

Languages

  • Japanese

Credentials & Experience

Education & Training

  • BA, 1992 Biology, Kobe University (Japan)
  • PhD, 1998 Microbiology, Kyoto University (Japan)

Honors & Awards

2006 University of Washington Center for AIDS Research (CFAR) New Investigator Award

Research

The Yamashita Lab studies the molecular and cellular basis of HIV-1 replication. A major research focus in our lab is the viral capsid, a key molecular complex that encloses viral and host molecules essential for infection. Multifaceted roles played by the viral capsid contribute to shaping the unique HIV-1 biology, including the ability to infect non-dividing cells, preferential integration within active genes and innate immune evasion. Studies of our group include a detailed analysis of capsid evolution, capsid-host interactions and mechanisms of capsid-targeting antivirals. Results from these experiments will have broad implications for basic research on HIV-1 biology as well as for therapeutic applications, such as drug development targeting the viral capsid. Another direction of our lab is single-cell analysis of HIV-1 replication. A major goal of this project is to gain quantitative, mechanistic, and biological insights into cell-to-cell variation in HIV-1 transmissibility. Towards this end, we are developing single-cell assays to quantify virus production and transmission by individual virus-infected cells.

HIV-1 Capsid

The major goal of this project is to elucidate how the HIV-1 capsid coordinates multiple post-entry events to maximize viral fitness. The viral capsid undergoes structural and functional "metamorphosis" to yield pre-integration complexes after completion of reverse transcription. Core disassembly is regulated by both intrinsic capsid stability and capsid binding proteins and influences cytoplasmic and nuclear events, such as reverse transcription, nuclear entry and integration targeting. We employ a broad range of experimental approaches to comprehensively understand viral and cellular determinants for core stability and disassembly and to delineate their functional significance in capsid-mediated intracellular processes, including HIV-1 immune evasion. Results from these experiments will have broad implications for basic research on HIV-1 biology as well as for therapeutic applications, including drug development targeting the viral capsid.

Single-Cell Analysis of HIV-1 Replication 

Recent technological advances in single-cell techniques revealed a considerable degree of functional and phenotypic heterogeneity between individual cells. It is unclear how such cell-to-cell variation affects HIV-1 transmission by virus-producing cells. The major goal of this project is to gain quantitative, mechanistic and biological insights into cell-to-cell variation in HIV-1 transmissibility at the single-cell level. Towards this end, we are developing single-cell assays to quantify virus production and transmission by individual virus-infected cells in vitro.

Selected Publications

  • Siddiqui MA, Yamashita M. Toll-Like Receptor (TLR) Signaling Enables Cyclic GMP-AMP Synthase (cGAS) Sensing of HIV-1 Infection in Macrophages. mBio. 2021 Dec 21;12(6):e0281721. doi: 10.1128/mBio.02817-21. Epub 2021 Nov 30. PubMed PMID: 34844429; PubMed Central PMCID: PMC8630538.
  • Saito A, Yamashita M. HIV-1 capsid variability: viral exploitation and evasion of capsid-binding molecules. Retrovirology. 2021 Oct 26;18(1):32. doi: 10.1186/s12977-021-00577-x. Review. PubMed PMID: 34702294; PubMed Central PMCID: PMC8549334.
  • Wang P, Liu L, Nair MS, Yin MT, Luo Y, Wang Q, Yuan T, Mori K, Solis AG, Yamashita M, Garg A, Purpura LJ, Laracy JC, Yu J, Joshua-Tor L, Sodroski J, Huang Y, Ho DD. SARS-CoV-2 neutralizing antibody responses are more robust in patients with severe disease. Emerg Microbes Infect. 2020 Dec;9(1):2091-2093. doi: 10.1080/22221751.2020.1823890. PubMed PMID: 32930052; PubMed Central PMCID: PMC7534308.
  • Sultana T, Mamede JI, Saito A, Ode H, Nohata K, Cohen R, Nakayama EE, Iwatani Y, Yamashita M, Hope TJ, Shioda T. 2019. Multiple pathways to avoid IFN-╬▓ sensitivity of HIV-1 by mutations in capsid. J Virol.2019 Dec 1;93(23).doi: 10.1128/JVI.00986-19.
  • Siddiqui MA, Saito A, Halambage UD, Ferhadian D, Fischer DK, Francis AC, Melikyan GB, Ambrose Z, Aiken C, Yamashita M. 2019. A Novel Phenotype Links HIV-1 Capsid Stability to cGAS-Mediated DNA Sensing. J Virol.2019 Aug 15;93(16).doi: 10.1128/JVI.00706-19.
  • Fischer DK, Saito A, Kline C, Cohen R, Watkins SC, Yamashita M, Ambrose Z. 2019. CA Mutation N57A Has Distinct Strain-Specific HIV-1 Capsid Uncoating and Infectivity Phenotypes. J Virol.2019 May 1;93(9).doi: 10.1128/JVI.00214-19.
  • Kane M, Rebensburg SV, Takata MA, Zang TM, Yamashita M, Kvaratskhelia M, Bieniasz PD. 2018. Nuclear pore heterogeneity influences HIV-1 infection and the antiviral activity of MX2. Elife.2018 Aug 7;7.doi: 10.7554/eLife.35738.
  • Yamashita M, Engelman AN. 2017. Capsid-Dependent Host Factors in HIV-1 Infection. Trends Microbiol.2017 Sep;25(9):741-755.doi: 10.1016/j.tim.2017.04.004.Epub 2017 May 18.
  • Saito A, Henning MS, Serrao E, Dubose BN, Teng S, Huang J, Li X, Saito N, Roy SP, Siddiqui MA, Ahn J, Tsuji M, Hatziioannou T, Engelman AN, Yamashita M. Capsid-CPSF6 Interaction Is Dispensable for HIV-1 Replication in Primary Cells but Is Selected during Virus Passage In Vivo. J Virol. 2016. 90. 6918-6935.
  • Saito A, Ferhadian D, Sowd GA, Serrao E, Shi J, Halambage UD, Teng S, Soto J, Siddiqui MA, Engelman AN, Aiken C, Yamashita M. Roles of Capsid-Interacting Host Factors in Multimodal Inhibition of HIV-1 by PF74. J Virol. 2016. 90. 5808-5823.
  • Henning MS, Dubose BN, Burse MJ, Aiken C, Yamashita M. In vivo functions of CPSF6 for HIV-1 as revealed by HIV-1 capsid evolution in HLA-B27-positive subjects. PLoS Pathog. 2014. 10. e1003868.
  • Kane M, Yadav SS, Bitzegeio J, Kutluay SB, Zang T, Wilson SJ, Schoggins JW, Rice CM, Yamashita M, Hatziioannou T, Bieniasz PD. MX2 is an interferon-induced inhibitor of HIV-1 infection. Nature. 2013. 502. 563-566.
  • Yamashita M, Emerman M. Cellular restriction targeting viral capsids perturbs human immunodeficiency virus type 1 infection of nondividing cells. J Virol. 2009. 83. 9835-9843.
  • Yamashita M, Perez O, Hope TJ, Emerman M. Evidence for direct involvement of the capsid protein in HIV infection of nondividing cells. PLoS Pathog. 2007. 3. 1502-1510.
  • Lewinski MK, Yamashita M, Emerman M, Ciuffi A, Marshall H, Crawford G, Collins F, Shinn P, Leipzig J, Hannenhalli S, Berry CC, Ecker JR, Bushman FD. Retroviral DNA integration: viral and cellular determinants of target-site selection. PLoS Pathog. 2006. 2. e60.
  • Ohkura S, Yamashita M, Ishida T, Babu PG, Koyanagi Y, Yamamoto N, Miura T, Hayami M. Phylogenetic heterogeneity of new HTLV type 1 isolates from southern India in subgroup A. AIDS Res Hum Retroviruses. 2005. 21. 325-330.
  • Yamashita M, Emerman M. The cell cycle independence of HIV infections is not determined by known karyophilic viral elements. PLoS Pathog. 2005. 1. e18.
  • Yamashita M, Emerman M. Capsid is a dominant determinant of retrovirus infectivity in nondividing cells. J Virol. 2004. 78. 5670-5678.
  • Yamaguchi-Kabata Y, Yamashita M, Ohkura S, Hayami M, Miura T. Linkage of amino acid variation and evolution of human immunodeficiency virus type 1 gp120 envelope glycoprotein (subtype B) with usage of the second receptor. J Mol Evol. 2004. 58. 333-340.
  • Takemura T, Yamashita M, Shimada MK, Ohkura S, Shotake T, Ikeda M, Miura T, Hayami M. High prevalence of simian T-lymphotropic virus type L in wild ethiopian baboons. J Virol. 2002. 76. 1642-1648.
  • Dvorin JD, Bell P, Maul GG, Yamashita M, Emerman M, Malim MH. Reassessment of the roles of integrase and the central DNA flap in human immunodeficiency virus type 1 nuclear import. J Virol. 2002. 76. 12087-12096.
  • Yamashita M, Ishida T, Ohkura S, Miura T, Hayami M. Phylogenetic characterization of a new HTLV type 1 from the Ainu in Japan. AIDS Res Hum Retroviruses. 2001. 17. 783-787.
  • Syrtsev AV, Yamashita M, Senyuta NB, Susova OY, Hayami M, Gurtsevitch VE. HTLV-I infection among Nivkhi people in Sakhalin: comparative serologic and phylogenetic analyses for 9 years. Int J Cancer. 2000. 87. 379-381.
  • Mboudjeka I, Zekeng L, Takehisa J, Miura T, Ido E, Yamashita M, Kaptue L, Hayami M. HIV type 1 genetic variability in the northern part of Cameroon. AIDS Res Hum Retroviruses. 1999. 15. 951-956.
  • Ohba K, Mizokami M, Kato T, Ueda R, Gurtsenvitch V, Senyuta N, Syrtsev A, Zoya K, Yamashita M, Hayami M. Seroprevalence of hepatitis B virus, hepatitis C virus and GB virus-C infections in Siberia. Epidemiol Infect. 1999. 122. 139-143.
  • Ohkura S, Yamashita M, Cartier L, Tanabe DG, Hayami M, Sonoda S, Tajima K. Identification and phylogenetic characterization of a human T-cell leukaemia virus type I isolate from a native inhabitant (Rapa Nui) of Easter Island. J Gen Virol. 1999. 80 ( Pt 8). 1995-2001.
  • Ohkura S, Yanagihara R, Yamashita M, Hayami M. Phylogenetic relatedness of HTLV type I from Bellona, a Polynesian outlier within the Solomon Islands, to HTLV type I from Japan and far Eastern Asia. AIDS Res Hum Retroviruses. 1999. 15. 1041-1045.
  • Yamashita M, Veronesi R, Menna-Barreto M, Harrington WJ, Jr., Sampio C, Brites C, Badaro R, Andrade-Filho AS, Okhura S, Igarashi T, Takehisa J, Miura T, Chamone D, Bianchini O, Jardim C, Sonoda S, Hayami M. Molecular epidemiology of human T-cell leukemia virus type I (HTLV-1) Brazil: the predominant HTLV-1s in South America differ from HTLV-ls of Japan and Africa, as well as those of Japanese immigrants and their relatives in Brazil. Virology. 1999. 261. 59-69.
  • Yamashita M, Picchio G, Veronesi R, Ohkura S, Bare P, Hayami M. HTLV-Is in Argentina are phylogenetically similar to those of other South American countries, but different from HTLV-Is in Africa. J Med Virol. 1998. 55. 152-160.
  • Takehisa J, Zekeng L, Ido E, Mboudjeka I, Moriyama H, Miura T, Yamashita M, Gurtler LG, Hayami M, Kaptue L. Various types of HIV mixed infections in Cameroon. Virology. 1998. 245. 1-10.
  • Senyuta N, Syrtsev A, Yamashita M, Stepina V, Susova O, Scherbak L, Pavlish O, Hayami M, Gurtsevitch V. Sero-epidemiologic and phylogenetic studies of HTLV-I infection in 2 countries of the Caspian Sea region. Int J Cancer. 1998. 77. 488-493.
  • Lou H, Li HC, Kuwayama M, Yashiki S, Fujiyoshi T, Suehara M, Osame M, Yamashita M, Hayami M, Gurtsevich V, Ballas M, Imanishi T, Sonoda S. HLA class I and class II of the Nivkhi, an indigenous population carrying HTLV-I in Sakhalin, Far Eastern Russia. Tissue Antigens. 1998. 52. 444-451.
  • Ibuki K, Ido E, Setiyaningsih S, Yamashita M, Agus LR, Takehisa J, Miura T, Dondin S, Hayami M. Isolation of STLV-I from orangutan, a great ape species in Southeast Asia, and its relation to other HTLV-Is/STLV-Is. Jpn J Cancer Res. 1997. 88. 1-4.
  • Kato T, Mizokami M, Nakano T, Kondo Y, Ohba K, Orito E, Ueda R, Mukaide M, Gurtsevitch V, Syrtsev A, Ruzibakiev R, Abdurakhnamov M, Yamashita M, Hayami M. High prevalence of GB virus C/hepatitis G virus infection among the Jewish population in Uzbekistan. Virus Res. 1997. 48. 81-87.
  • Mboudjeka I, Zekeng L, Yamashita M, Takehisa J, Ido E, Miura T, Ohkura S, Ikeda M, Kaptue L, Hayami M. Prevalence and phylogenetic analysis of HTLV-I isolates in Cameroon, including those of the Baka Pygmy. Jpn J Cancer Res. 1997. 88. 619-624.
  • Miura T, Yamashita M, Zaninovic V, Cartier L, Takehisa J, Igarashi T, Ido E, Fujiyoshi T, Sonoda S, Tajima K, Hayami M. Molecular phylogeny of human T-cell leukemia virus type I and II of Amerindians in Colombia and Chile. J Mol Evol. 1997. 44 Suppl 1. S76-82.
  • Takehisa J, Osei-Kwasi M, Ayisi NK, Hishida O, Miura T, Igarashi T, Brandful J, Ampofo W, Netty VB, Mensah M, Yamashita M, Ido E, Hayami M. Phylogenetic analysis of HIV type 2 in Ghana and intrasubtype recombination in HIV type 2. AIDS Res Hum Retroviruses. 1997. 13. 621-623.
  • Takehisa J, Osei-Kwasi M, Ayisi NK, Hishida O, Miura T, Igarashi T, Brandful J, Ampofo W, Netty VB, Mensah M, Yamashita M, Ido E, Hayami M. Phylogenetic analysis of human immunodeficiency virus 1 in Ghana. Acta Virol. 1997. 41. 51-54.
  • Takehisa J, Zekeng L, Miura T, Ido E, Yamashita M, Mboudjeka I, Gurtler LG, Hayami M, Kaptue L. Triple HIV-1 infection with group O and Group M of different clades in a single Cameroonian AIDS patient. J Acquir Immune Defic Syndr Hum Retrovirol. 1997. 14. 81-82.
  • Yamashita M, Takehisa J, Miura T, Ido E, Becker WB, Robson BA, Becker ML, Hayami M. Presence of the widespread subtype of HTLV-I in South Africa. AIDS Res Hum Retroviruses. 1995. 11. 645-647.
  • Yamashita M, Seniuta NB, Pavlish OA, Miura T, Syrtsev AV, Gurova EP, Stepina VN, Ibuki K, Susova O, Shcherbak LN, et al. Distribution and phylogenetic analysis of HTLV-I isolates, persisting in the Russian Far East. Mol Biol (Mosk). 1995. 29. 1172-1182.
  • Yamashita M, Kitze B, Miura T, Weber T, Fujiyoshi T, Takehisa J, Chen JL, Sonoda S, Hayami M. The phylogenetic relationship of HTLV type I from non-Mashhadi Iranians to that from Mashhadi Jews. AIDS Res Hum Retroviruses. 1995. 11. 1533-1535.
  • Yamashita M, Achiron A, Miura T, Takehisa J, Ido E, Igarashi T, Ibuki K, Osame M, Sonoda S, Melamed E, Hayami M, Shohat B. HTLV-I from Iranian Mashhadi Jews in Israel is phylogenetically related to that of Japan, India, and South America rather than to that of Africa and Melanesia. Virus Genes. 1995. 10. 85-90.
  • Chen J, Zekeng L, Yamashita M, Takehisa J, Miura T, Ido E, Mboudjeka I, Tsague JM, Hayami M, Kaptue L. HTLV type I isolated from a Pygmy in Cameroon is related to but distinct from the known central African type. AIDS Res Hum Retroviruses. 1995. 11. 1529-1531.
  • Miura T, Fukunaga T, Igarashi T, Yamashita M, Ido E, Funahashi S, Ishida T, Washio K, Ueda S, Hashimoto K, Yoshida M, Osame M, Singhal B, Zaninovic V, Cartier L, Sonoda S, Tajima K, Ina Y, Gojobori T, Hayami M. Phylogenetic subtypes of human T-lymphotropic virus type I and their relations to the anthropological background. Proc Natl Acad Sci U S A. 1994. 91. 1124-1127.
  • Igarashi T, Yamashita M, Miura T, Osei-Kwasi M, Aysi NK, Shiraki H, Kurimura T, Hayami M. Isolation and genomic analysis of human T lymphotropic virus type II from Ghana. AIDS Res Hum Retroviruses. 1993. 9. 1039-1042.