Keywords
Last Name

Kei Yasuda, PhD

TitleAssistant Professor
InstitutionBoston University School of Medicine
DepartmentMedicine
DivisionNephrology
Address650 Albany St Evans Biomed Research Ctr
Boston MA 02118
Phone(617) 414-3338
ORCID ORCID Icon0000-0002-6791-4531
Other Positions
InstitutionBoston Medical Center

 Research Expertise & Professional Interests
“To the clinician, systemic lupus erythematosus is important because it is a potentially fatal disease that is easily confused with many other disorders. To the immunologist, lupus is intriguing because all the key components of the immune system are involved in the underlying mechanisms of the disease.”(Anisur Rahman, Ph.D., and David A. Isenberg, M.D. N Engl J Med. 2008 Feb 28;358(9):929-39.)

I have studied this devastating but interesting disease more than 10 years. Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by the presence of great diversity of autoantibodies against nucleic acids (DNA and RNA) and other autoantigens. The autoantibodies form immune complexes that deposit in various tissues including the kidney, causing inflammation and end-organ damage. Current medications are only partially effective and have severe side effects.

We are interested in the role of interferon regulatory factor-5 (IRF5) in the pathogenesis of SLE in mice and humans. We have shown that IRF5 in plasmacytoid dendritic cells is involved in the production of type I interferons (IFNs), which are pathogenic cytokines in SLE. We also found that IRF5 contributes to the formation of antibody-producing plasma cells in lupus-prone mice. Currently we investigate how IRF5 is involved in the plasma cell development and T cell differentiation.

Although there is no doubt that IRF5 is a potential target, “IRF5 inhibitors” for the treatment of SLE are not available at the moment. I seek collaborations to accelerate the development of potential drugs to cure SLE.

 Self-Described Keywords
  • Systemic lupus erythematosus
  • Interferon regulatory factor-5
  • plasmacytoid dendritic cells
  • plasma cells
  • Toll-like receptor-7
  • Toll-like receptor-9
  • autoimmune disease
 Publications
Publications listed below are automatically derived from MEDLINE/PubMed and other sources, which might result in incorrect or missing publications. Faculty can login to make corrections and additions.
List All   |   Timeline
  1. Duffau P, Menn-Josephy H, Cuda CM, Dominguez S, Aprahamian TR, Watkins AA, Yasuda K, Monach P, Lafyatis R, Rice LM, Kenneth Haines G, Gravallese EM, Baum R, Richez C, Perlman H, Bonegio RG, Rifkin IR. Promotion of Inflammatory Arthritis by Interferon Regulatory Factor 5 in a Mouse Model. Arthritis Rheumatol. 2015 Dec; 67(12):3146-57. PMID: 26315890.
    View in: PubMed
  2. Watkins AA, Yasuda K, Wilson GE, Aprahamian T, Xie Y, Maganto-Garcia E, Shukla P, Oberlander L, Laskow B, Menn-Josephy H, Wu Y, Duffau P, Fried SK, Lichtman AH, Bonegio RG, Rifkin IR. IRF5 deficiency ameliorates lupus but promotes atherosclerosis and metabolic dysfunction in a mouse model of lupus-associated atherosclerosis. J Immunol. 2015 Feb 15; 194(4):1467-79. PMID: 25595782.
    View in: PubMed
  3. Ericson JA, Duffau P, Yasuda K, Ortiz-Lopez A, Rothamel K, Rifkin IR, Monach PA. Gene expression during the generation and activation of mouse neutrophils: implication of novel functional and regulatory pathways. PLoS One. 2014; 9(10):e108553. PMID: 25279834.
    View in: PubMed
  4. Yasuda K, Watkins AA, Kochar GS, Wilson GE, Laskow B, Richez C, Bonegio RG, Rifkin IR. Interferon regulatory factor-5 deficiency ameliorates disease severity in the MRL/lpr mouse model of lupus in the absence of a mutation in DOCK2. PLoS One. 2014; 9(7):e103478. PMID: 25076492.
    View in: PubMed
  5. Yasuda K, Nündel K, Watkins AA, Dhawan T, Bonegio RG, Ubellacker JM, Marshak-Rothstein A, Rifkin IR. Phenotype and function of B cells and dendritic cells from interferon regulatory factor 5-deficient mice with and without a mutation in DOCK2. Int Immunol. 2013 May; 25(5):295-306. PMID: 23291967.
    View in: PubMed
  6. Richez C, Yasuda K, Bonegio RG, Watkins AA, Aprahamian T, Busto P, Richards RJ, Liu CL, Cheung R, Utz PJ, Marshak-Rothstein A, Rifkin IR. IFN regulatory factor 5 is required for disease development in the FcgammaRIIB-/-Yaa and FcgammaRIIB-/- mouse models of systemic lupus erythematosus. J Immunol. 2010 Jan 15; 184(2):796-806. PMID: 20007534.
    View in: PubMed
  7. Yasuda K, Richez C, Uccellini MB, Richards RJ, Bonegio RG, Akira S, Monestier M, Corley RB, Viglianti GA, Marshak-Rothstein A, Rifkin IR. Requirement for DNA CpG content in TLR9-dependent dendritic cell activation induced by DNA-containing immune complexes. J Immunol. 2009 Sep 1; 183(5):3109-17. PMID: 19648272.
    View in: PubMed
  8. Green NM, Laws A, Kiefer K, Busconi L, Kim YM, Brinkmann MM, Trail EH, Yasuda K, Christensen SR, Shlomchik MJ, Vogel S, Connor JH, Ploegh H, Eilat D, Rifkin IR, van Seventer JM, Marshak-Rothstein A. Murine B cell response to TLR7 ligands depends on an IFN-beta feedback loop. J Immunol. 2009 Aug 1; 183(3):1569-76. PMID: 19587008.
    View in: PubMed
  9. Lenert P, Yasuda K, Busconi L, Nelson P, Fleenor C, Ratnabalasuriar RS, Nagy PL, Ashman RF, Rifkin IR, Marshak-Rothstein A. DNA-like class R inhibitory oligonucleotides (INH-ODNs) preferentially block autoantigen-induced B-cell and dendritic cell activation in vitro and autoantibody production in lupus-prone MRL-Fas(lpr/lpr) mice in vivo. Arthritis Res Ther. 2009; 11(3):R79. PMID: 19476613.
    View in: PubMed
  10. Richez C, Yasuda K, Watkins AA, Akira S, Lafyatis R, van Seventer JM, Rifkin IR. TLR4 ligands induce IFN-alpha production by mouse conventional dendritic cells and human monocytes after IFN-beta priming. J Immunol. 2009 Jan 15; 182(2):820-8. PMID: 19124725.
    View in: PubMed
  11. Aprahamian T, Bonegio RG, Richez C, Yasuda K, Chiang LK, Sato K, Walsh K, Rifkin IR. The peroxisome proliferator-activated receptor gamma agonist rosiglitazone ameliorates murine lupus by induction of adiponectin. J Immunol. 2009 Jan 1; 182(1):340-6. PMID: 19109165.
    View in: PubMed
  12. Yasuda K, Richez C, Maciaszek JW, Agrawal N, Akira S, Marshak-Rothstein A, Rifkin IR. Murine dendritic cell type I IFN production induced by human IgG-RNA immune complexes is IFN regulatory factor (IRF)5 and IRF7 dependent and is required for IL-6 production. J Immunol. 2007 Jun 1; 178(11):6876-85. PMID: 17513736.
    View in: PubMed
  13. Yoshinaga T, Yasuda K, Ogawa Y, Nishikawa M, Takakura Y. DNA and its cationic lipid complexes induce CpG motif-dependent activation of murine dendritic cells. Immunology. 2007 Mar; 120(3):295-302. PMID: 17199803.
    View in: PubMed
  14. Yasuda K, Rutz M, Schlatter B, Metzger J, Luppa PB, Schmitz F, Haas T, Heit A, Bauer S, Wagner H. CpG motif-independent activation of TLR9 upon endosomal translocation of "natural" phosphodiester DNA. Eur J Immunol. 2006 Feb; 36(2):431-6. PMID: 16421948.
    View in: PubMed
  15. Yasuda K, Wagner H, Takakura Y. Role of immunostimulatory DNA and TLR9 in gene therapy. Crit Rev Ther Drug Carrier Syst. 2006; 23(2):89-110. PMID: 16952273.
    View in: PubMed
  16. Ogawa Y, Yoshinaga T, Yasuda K, Nishikawa M, Takakura Y. The uptake and degradation of DNA is impaired in macrophages and dendritic cells from NZB/W F(1) mice. Immunol Lett. 2005 Oct 15; 101(1):32-40. PMID: 15979158.
    View in: PubMed
  17. Yasuda K, Yu P, Kirschning CJ, Schlatter B, Schmitz F, Heit A, Bauer S, Hochrein H, Wagner H. Endosomal translocation of vertebrate DNA activates dendritic cells via TLR9-dependent and -independent pathways. J Immunol. 2005 May 15; 174(10):6129-36. PMID: 15879108.
    View in: PubMed
  18. Yu P, Constien R, Dear N, Katan M, Hanke P, Bunney TD, Kunder S, Quintanilla-Martinez L, Huffstadt U, Schröder A, Jones NP, Peters T, Fuchs H, de Angelis MH, Nehls M, Grosse J, Wabnitz P, Meyer TP, Yasuda K, Schiemann M, Schneider-Fresenius C, Jagla W, Russ A, Popp A, Josephs M, Marquardt A, Laufs J, Schmittwolf C, Wagner H, Pfeffer K, Mudde GC. Autoimmunity and inflammation due to a gain-of-function mutation in phospholipase C gamma 2 that specifically increases external Ca2+ entry. Immunity. 2005 Apr; 22(4):451-65. PMID: 15845450.
    View in: PubMed
  19. Yasuda K, Ogawa Y, Yamane I, Nishikawa M, Takakura Y. Macrophage activation by a DNA/cationic liposome complex requires endosomal acidification and TLR9-dependent and -independent pathways. J Leukoc Biol. 2005 Jan; 77(1):71-9. PMID: 15496451.
    View in: PubMed
  20. Yasuda K, Kawano H, Yamane I, Ogawa Y, Yoshinaga T, Nishikawa M, Takakura Y. Restricted cytokine production from mouse peritoneal macrophages in culture in spite of extensive uptake of plasmid DNA. Immunology. 2004 Mar; 111(3):282-90. PMID: 15009428.
    View in: PubMed
  21. Kawase A, Nomura T, Yasuda K, Kobayashi N, Hashida M, Takakura Y. Disposition and gene expression characteristics in solid tumors and skeletal muscle after direct injection of naked plasmid DNA in mice. J Pharm Sci. 2003 Jun; 92(6):1295-304. PMID: 12761818.
    View in: PubMed
  22. Yoshinaga T, Yasuda K, Ogawa Y, Takakura Y. Efficient uptake and rapid degradation of plasmid DNA by murine dendritic cells via a specific mechanism. Biochem Biophys Res Commun. 2002 Dec 6; 299(3):389-94. PMID: 12445812.
    View in: PubMed
  23. Sakurai F, Terada T, Yasuda K, Yamashita F, Takakura Y, Hashida M. The role of tissue macrophages in the induction of proinflammatory cytokine production following intravenous injection of lipoplexes. Gene Ther. 2002 Aug; 9(16):1120-6. PMID: 12140741.
    View in: PubMed
  24. Yasuda K, Ogawa Y, Kishimoto M, Takagi T, Hashida M, Takakura Y. Plasmid DNA activates murine macrophages to induce inflammatory cytokines in a CpG motif-independent manner by complex formation with cationic liposomes. Biochem Biophys Res Commun. 2002 Apr 26; 293(1):344-8. PMID: 12054606.
    View in: PubMed
  25. Nomura T, Yasuda K, Yamada T, Okamoto S, Mahato RI, Watanabe Y, Takakura Y, Hashida M. Gene expression and antitumor effects following direct interferon (IFN)-gamma gene transfer with naked plasmid DNA and DC-chol liposome complexes in mice. Gene Ther. 1999 Jan; 6(1):121-9. PMID: 10341884.
    View in: PubMed
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