Kei Yasuda PhD

Assistant Professor, Nephrology

650 Albany St | (617) 414-3338
Kei Yasuda
Sections

Nephrology

Biography

“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 intellectually challenging 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.

My recent interest is neutrophil activation induced by immune complexes. Studies have shown that neutrophils release reactive oxygen species (ROS) and neutrophil extracellular traps (NETs) upon stimulation with RNA-containing immune complexes. My new goal is to investigate whether other immune complexes from SLE patients can activate neutrophils, and what kind of signaling pathways are involved in the activation.

I am also interested in the role of interferon regulatory factor-5 (IRF5) in the pathogenesis of SLE. Genetic studies have shown that mutations of IRF5 are associated with the disease severity of SLE. Using IRF5-deficient mice and lupus-prone mice, we have shown that IRF5 is a critical regulatory of SLE. In addition, we have shown that sera from SLE patients are able to activate plasmacytoid dendritic cells (pDC) to induce type I IFN , which is a pathogenic cytokines in SLE. We demonstrated that the type I IFN production from pDC is dependent on toll-like receptor-7 (TLR7) and IRF5. We investigate whether IRF5 is involved in the activation of B cells and T cells.

Education

PhD, Kyoto University, 2003

MS, Kyoto University, 2000

BS, Kyoto University, 1998

Publications

Published on 8/9/2021

Pellerin A, Yasuda K, Cohen-Bucay A, Sandra V, Shukla P, Jr BKH, Nündel K, Viglianti GA, Xie Y, Klein U, Tan Y, Bonegio RG, Rifkin IR. Monoallelic IRF5 deficiency in B cells prevents murine lupus. JCI Insight. 2021 Aug 09; 6(15). PMID: 34197340.

Published on 4/29/2021

Kawakami R, Kitagawa Y, Chen KY, Arai M, Ohara D, Nakamura Y, Yasuda K, Osaki M, Mikami N, Lareau CA, Watanabe H, Kondoh G, Hirota K, Ohkura N, Sakaguchi S. Distinct Foxp3 enhancer elements coordinate development, maintenance, and function of regulatory T cells. Immunity. 2021 05 11; 54(5):947-961.e8. PMID: 33930308.

Published on 2/4/2020

Lee J, Zhang J, Chung YJ, Kim JH, Kook CM, González-Navajas JM, Herdman DS, Nürnberg B, Insel PA, Corr M, Mo JH, Tao A, Yasuda K, Rifkin IR, Broide DH, Sciammas R, Webster NJ, Raz E. Inhibition of IRF4 in dendritic cells by PRR-independent and -dependent signals inhibit Th2 and promote Th17 responses. Elife. 2020 02 04; 9. PMID: 32014112.

Published on 12/27/2019

Lyle C, Richards S, Yasuda K, Napoleon MA, Walker J, Arinze N, Belghasem M, Vellard I, Yin W, Ravid JD, Zavaro E, Amraei R, Francis J, Phatak U, Rifkin IR, Rahimi N, Chitalia VC. c-Cbl targets PD-1 in immune cells for proteasomal degradation and modulates colorectal tumor growth. Sci Rep. 2019 12 27; 9(1):20257. PMID: 31882749.

Published on 1/4/2019

Bonegio RG, Lin JD, Beaudette-Zlatanova B, York MR, Menn-Josephy H, Yasuda K. Lupus-Associated Immune Complexes Activate Human Neutrophils in an Fc?RIIA-Dependent but TLR-Independent Response. J Immunol. 2019 02 01; 202(3):675-683. PMID: 30610165.

Published on 4/11/2017

Choo MK, Sano Y, Kim C, Yasuda K, Li XD, Lin X, Stenzel-Poore M, Alexopoulou L, Ghosh S, Latz E, Rifkin IR, Chen ZJ, Stewart GC, Chong H, Park JM. TLR sensing of bacterial spore-associated RNA triggers host immune responses with detrimental effects. J Exp Med. 2017 May 01; 214(5):1297-1311. PMID: 28400473.

Published on 12/1/2015

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.

Published on 1/16/2015

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.

Published on 10/3/2014

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.

Published on 7/30/2014

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 full list of 31 publications.