Profile

Mohamed Oukka, PhD

Mohamed Oukka, PhD

Children's Title: Principal Investigator

Academic Title: Assistant Professor of Pediatrics / Adjunct Assistant Professor of Immunology, UW School of Medicine

Research Center: Center for Immunity and Immunotherapies

"While training at Harvard, I listened to a young mother, a multiple sclerosis (MS) patient, describe her daily struggle with this terrible disease. I was moved by her words and found myself driven to find a cure for MS. Since then, I have dedicated my scientific career to finding cures for autoimmune diseases and have used my training to develop research on possible treatments and eventual cures for MS. I firmly believe that my work in this field will be crucial for designing better therapies to treat autoimmune diseases. The best reward for my research would be making a positive difference in people’s lives."

Mohamed Oukka, PhD, is principal investigator in the Division of Immunology at Seattle Children’s Hospital, and is assistant professor in the Department of Pediatrics and adjunct assistant professor in the Department of Immunology at the University of Washington School of Medicine.

He obtained his PhD in Immunology from the University of Pierre and Marie Curie and Pasteur Institute in France and was assistant professor of Neurology at Harvard Medical School before joining the Center for Immunity and Immunotherapies at Seattle Children’s Research Institute. Autoimmune diseases represent a major threat to public health with >10 million Americans suffering from autoimmune disorders. Understanding how these diseases can be initiated and regulated is critical to the design of new therapeutics to treat autoimmune diseases. The overall goal of Dr. Oukka’s research is to understand the underlying mechanisms that govern the generation and the function of immuno-regulatory subsets of T cells called regulatory T cells. This subset of cells is crucial for preventing the development of autoimmune diseases. Dr. Oukka’s broad vision for the future is to identify genetic modifiers of human autoimmune diseases, characterize genes that are necessary for the development of autoimmunity, validate these genes as targets for the development of therapies and develop a platform of genetically modified mice that will help us evaluate novel therapeutic agents. Dr. Oukka is an active member of the American Society of Immunology.

Making A Difference

Overview

Clinical Interests

Multiple Sclerosis, Lupus, Crohn's Disease, Cancer

Research Description

Professional History:
Dr. Oukka received his Ph.D. in Immunology at the University of Paris and Pasteur Institute (France) in 1997. Prior to joining the University of Washington and Seattle Children's Research Institute in 2009, he held positions at Brigham and Women's Hospital and Harvard medical School in Boston.

Research Description:
The adaptive immune system is required to clear pathogens. However, under specific conditions, T cells from the adaptive immune system are dysregulated, and attack the body's own tissues, leading to the development of autoimmune and graft versus host diseases. Autoimmune diseases represent a major threat to public health with >10 million Americans suffering from autoimmune disorders. Understanding how these diseases can be initiated and regulated is critical to the design of new therapeutics to treat autoimmune diseases.

Multiple Sclerosis is an autoimmune disease in which myelin is the target of an immune attack. It is believed that a subset of cells called regulatory T cells (Tregs) have a major function in preventing the auto-aggressive cells from attacking the self-myelin. What are these protective cells? How are they generated? How do they protect self-myelin from damage? These questions are the focus of my research. These Treg cells do not seem to work effectively in patients with MS. Treatment with ex vivo-generated Tregs has been regarded as a potentially attractive therapeutic approach for autoimmune diseases. However, the dynamics and function of Treg in autoimmunity are not well understood. Our novel research model has considerably enhanced our understanding of how Tregs are generated in vivo and how they inhibit myelin damage. We have found that Tregs expand in the peripheral lymphoid compartment and readily accumulate in the central nervous system (CNS), but do not prevent the onset of disease. Tregs isolated from the CNS are effective in suppressing naive T cells, but fail to control CNS-derived encephalitogenic T cells that secrete IL-6 and TNF. Our data suggest that in order for Tregs to effectively control autoimmune reactions in the target organ, it may also be necessary to control tissue inflammation.

Now we have ongoing studies focused on elucidating the specific mechanisms by which Tregs fulfill their suppressive function and identifying mechanisms by IL-6 produced during inflammation that inhibit Treg functions. The mechanisms that enhance and those that inhibit functions of Treg cells will have direct impact on developing potential immunomodulatory therapies for autoimmunity.

Early on in my carreer as molecular immunologist I was struck by people with MS and how their immune systems were attacking their own cells and organs. MS is so striking in young adults and such a debilitating disease. When a young mother has MS and is disabled, taking care of her own kids can be a challenge. MS really affects the whole family. I am interested in applied-science that leads to drug discoveries to help patients. If my research can make a difference in people's lives, for me that's the best reward.

Research Focus Area

Autoimmune Disorders, Immunology

Awards and Honors

Award Name Award Description Awarded By Award Date
Award RG3882-A1 (PI) - Multiple Sclerosis Society National Multiple Sclerosis Society Jan. 1, 2009

Publications

  • Petermann F, Rothhammer V, Claussen MC, Haas JD, Blanco LR, Heink S, Prinz I, Hemmer B, Kuchroo VK, Oukka M, Korn T
    γδ T cells enhance autoimmunity by restraining regulatory T cell responses via an interleukin-23-dependent mechanism.
    Immunity , 2010 Sept. 24 : 351-63
  • Kyttaris VC, Zhang Z, Kuchroo VK, Oukka M, Tsokos GC
    Cutting edge: IL-23 receptor deficiency prevents the development of lupus nephritis in C57BL/6-lpr/lpr mice.
    Journal of immunology (Baltimore, Md. : 1950) , 2010 May 1 : 4605-9
  • Tartar DM, VanMorlan AM, Wan X, Guloglu FB, Jain R, Haymaker CL, Ellis JS, Hoeman CM, Cascio JA, Dhakal M, Oukka M, Zaghouani H
    FoxP3+RORgammat+ T helper intermediates display suppressive function against autoimmune diabetes.
    Journal of immunology (Baltimore, Md. : 1950) , 2010 Apr, 1 : 3377-85
  • Quintana FJ, Iglesias AH, Farez MF, Caccamo M, Burns EJ, Kassam N, Oukka M, Weiner HL
    Adaptive autoimmunity and Foxp3-based immunoregulation in zebrafish.
    PloS one , 2010 Mar. 5 : e9478
  • Riol-Blanco L, Lazarevic V, Awasthi A, Mitsdoerffer M, Wilson BS, Croxford A, Waisman A, Kuchroo VK, Glimcher LH, Oukka M
    IL-23 receptor regulates unconventional IL-17-producing T cells that control bacterial infections.
    Journal of immunology (Baltimore, Md. : 1950) , 2010 Feb. 15 : 1710-20
  • Araki M, Chung D, Liu S, Rainbow DB, Chamberlain G, Garner V, Hunter KM, Vijayakrishnan L, Peterson LB, Oukka M, Sharpe AH, Sobel R, Kuchroo VK, Wicker LS
    Genetic evidence that the differential expression of the ligand-independent isoform of CTLA-4 is the molecular basis of the Idd5.1 type 1 diabetes region in nonobese diabetic mice.
    Journal of immunology (Baltimore, Md. : 1950) , 2009 Oct. 15 : 5146-57
  • Alshwaimi E, Purcell P, Kawai T, Sasaki H, Oukka M, Campos-Neto A, Stashenko P
    Regulatory T cells in mouse periapical lesions.
    Journal of endodontics , 2009 Sept. : 1229-33
  • Elyaman W, Bradshaw EM, Uyttenhove C, Dardalhon V, Awasthi A, Imitola J, Bettelli E, Oukka M, van Snick J, Renauld JC, Kuchroo VK, Khoury SJ
    IL-9 induces differentiation of TH17 cells and enhances function of FoxP3+ natural regulatory T cells.
    Proceedings of the National Academy of Sciences of the United States of America , 2009 Aug. 4 : 12885-90
  • Awasthi A, Riol-Blanco L, Jäger A, Korn T, Pot C, Galileos G, Bettelli E, Kuchroo VK, Oukka M
    Cutting edge: IL-23 receptor gfp reporter mice reveal distinct populations of IL-17-producing cells.
    Journal of immunology (Baltimore, Md. : 1950) , 2009 May 15 : 5904-8
  • Ochs HD, Oukka M, Torgerson TR
    TH17 cells and regulatory T cells in primary immunodeficiency diseases.
    The Journal of allergy and clinical immunology , 2009 May : 977-83; quiz 984-5
  • Edgerton C, Crispín JC, Moratz CM, Bettelli E, Oukka M, Simovic M, Zacharia A, Egan R, Chen J, Dalle Lucca JJ, Juang YT, Tsokos GC
    IL-17 producing CD4+ T cells mediate accelerated ischemia/reperfusion-induced injury in autoimmunity-prone mice.
    Clinical immunology (Orlando, Fla.) , 2009 Mar. : 313-21
  • Korn T, Bettelli E, Oukka M, Kuchroo VK
    IL-17 and Th17 Cells.
    Annual review of immunology , 2009 : 485-517
  • Crispín JC, Oukka M, Bayliss G, Cohen RA, Van Beek CA, Stillman IE, Kyttaris VC, Juang YT, Tsokos GC
    Expanded double negative T cells in patients with systemic lupus erythematosus produce IL-17 and infiltrate the kidneys.
    Journal of immunology (Baltimore, Md. : 1950) , 2008 Dec. 15 : 8761-6
  • Dardalhon V, Awasthi A, Kwon H, Galileos G, Gao W, Sobel RA, Mitsdoerffer M, Strom TB, Elyaman W, Ho IC, Khoury S, Oukka M, Kuchroo VK
    IL-4 inhibits TGF-beta-induced Foxp3+ T cells and, together with TGF-beta, generates IL-9+ IL-10+ Foxp3(-) effector T cells.
    Nature immunology , 2008 Dec. : 1347-55
  • Korn T, Mitsdoerffer M, Croxford AL, Awasthi A, Dardalhon VA, Galileos G, Vollmar P, Stritesky GL, Kaplan MH, Waisman A, Kuchroo VK, Oukka M
    IL-6 controls Th17 immunity in vivo by inhibiting the conversion of conventional T cells into Foxp3+ regulatory T cells.
    Proceedings of the National Academy of Sciences of the United States of America , 2008 Nov. 25 : 18460-5
  • Feng G, Gao W, Strom TB, Oukka M, Francis RS, Wood KJ, Bushell A
    Exogenous IFN-gamma ex vivo shapes the alloreactive T-cell repertoire by inhibition of Th17 responses and generation of functional Foxp3+ regulatory T cells.
    European journal of immunology , 2008 Sept. : 2512-27
  • Xiao S, Jin H, Korn T, Liu SM, Oukka M, Lim B, Kuchroo VK
    Retinoic acid increases Foxp3+ regulatory T cells and inhibits development of Th17 cells by enhancing TGF-beta-driven Smad3 signaling and inhibiting IL-6 and IL-23 receptor expression.
    Journal of immunology (Baltimore, Md. : 1950) , 2008 Aug. 15 : 2277-84
  • Yang L, Anderson DE, Baecher-Allan C, Hastings WD, Bettelli E, Oukka M, Kuchroo VK, Hafler DA
    IL-21 and TGF-beta are required for differentiation of human T(H)17 cells.
    Nature , 2008 July 17 : 350-2
  • Bettelli E, Korn T, Oukka M, Kuchroo VK
    Induction and effector functions of T(H)17 cells.
    Nature , 2008 June 19 : 1051-7
  • Quintana FJ, Basso AS, Iglesias AH, Korn T, Farez MF, Bettelli E, Caccamo M, Oukka M, Weiner HL
    Control of T(reg) and T(H)17 cell differentiation by the aryl hydrocarbon receptor.
    Nature , 2008 May 1 : 65-71
  • Awasthi A, Carrier Y, Peron JP, Bettelli E, Kamanaka M, Flavell RA, Kuchroo VK, Oukka M, Weiner HL
    A dominant function for interleukin 27 in generating interleukin 10-producing anti-inflammatory T cells.
    Nature immunology , 2007 Dec. : 1380-9
  • Korn T, Oukka M, Kuchroo V, Bettelli E
    Th17 cells: effector T cells with inflammatory properties.
    Seminars in immunology , 2007 Dec. : 362-71
  • Moisan J, Grenningloh R, Bettelli E, Oukka M, Ho IC
    Ets-1 is a negative regulator of Th17 differentiation.
    The Journal of experimental medicine , 2007 Nov. 26 : 2825-35
  • Korn T, Anderson AC, Bettelli E, Oukka M
    The dynamics of effector T cells and Foxp3+ regulatory T cells in the promotion and regulation of autoimmune encephalomyelitis.
    Journal of neuroimmunology , 2007 Nov. : 51-60
  • Elyaman W, Bradshaw EM, Wang Y, Oukka M, Kivisäkk P, Chiba S, Yagita H, Khoury SJ
    JAGGED1 and delta1 differentially regulate the outcome of experimental autoimmune encephalomyelitis.
    Journal of immunology (Baltimore, Md. : 1950) , 2007 Nov. 1 : 5990-8
  • Oukka M
    Interplay between pathogenic Th17 and regulatory T cells.
    Annals of the rheumatic diseases , 2007 Nov. : iii87-90
  • Zhong X, Gao W, Degauque N, Bai C, Lu Y, Kenny J, Oukka M, Strom TB, Rothstein TL
    Reciprocal generation of Th1/Th17 and T(reg) cells by B1 and B2 B cells.
    European journal of immunology , 2007 Sept. : 2400-4
  • Sun CM, Hall JA, Blank RB, Bouladoux N, Oukka M, Mora JR, Belkaid Y
    Small intestine lamina propria dendritic cells promote de novo generation of Foxp3 T reg cells via retinoic acid.
    The Journal of experimental medicine , 2007 Aug. 6 : 1775-85
  • Korn T, Oukka M
    Dynamics of antigen-specific regulatory T-cells in the context of autoimmunity.
    Seminars in immunology , 2007 Aug. : 272-8
  • Chung DT, Korn T, Richard J, Ruzek M, Kohm AP, Miller S, Nahill S, Oukka M
    Anti-thymocyte globulin (ATG) prevents autoimmune encephalomyelitis by expanding myelin antigen-specific Foxp3+ regulatory T cells.
    International immunology , 2007 Aug. : 1003-10
  • Korn T, Bettelli E, Gao W, Awasthi A, Jäger A, Strom TB, Oukka M, Kuchroo VK
    IL-21 initiates an alternative pathway to induce proinflammatory T(H)17 cells.
    Nature , 2007 July 26 : 484-7
  • Deaglio S, Dwyer KM, Gao W, Friedman D, Usheva A, Erat A, Chen JF, Enjyoji K, Linden J, Oukka M, Kuchroo VK, Strom TB, Robson SC
    Adenosine generation catalyzed by CD39 and CD73 expressed on regulatory T cells mediates immune suppression.
    The Journal of experimental medicine , 2007 June 11 : 1257-65
  • Bettelli E, Oukka M, Kuchroo VK
    T(H)-17 cells in the circle of immunity and autoimmunity.
    Nature immunology , 2007 Apr, : 345-50
  • Korn T, Reddy J, Gao W, Bettelli E, Awasthi A, Petersen TR, Bäckström BT, Sobel RA, Wucherpfennig KW, Strom TB, Oukka M, Kuchroo VK
    Myelin-specific regulatory T cells accumulate in the CNS but fail to control autoimmune inflammation.
    Nature medicine , 2007 Apr, : 423-31

Presentations

Presentations Title Event Location Date
Role of Th17 Cells in Autoimmunity 15. Department of Rheumatology, University of Washington Seattle, WA Nov. 16, 2009
Interplay Between Th17 and Regulatory T Cells in Autoimmunity Forsythe Institute Boston, Massachusetts June 4, 2009
Regulatory T Cells and IL-17 Producing Cells in Immunity and Autoimmunity 13. Center of Research CHUM-Notre Dame Montreal, Canada May 21, 2009
Regulatory T Cells and IL-17 Producing Cells in Immunity and Autoimmunity 16. Department of Immunology, University of Washington Seattle, WA Jan. 23, 2009