Helena Reijonen, Ph.D.
- Autoreactive T Cells in Type 1 Diabetes
- Monitoring of T Cell Responses in Disease
- Mechanisms of Autoimmunity
Associate Professor, Department of Immunology & Theranostics
Helena Reijonen, Ph.D., is an associate professor in the Department of Immunology and Theranostics within the Diabetes & Metabolism Research Institute.
Education & Experience
1994, Ph.D., Ilonen laboratory, Immunogenetics, Department of Microbiology, University of Oulu and University of Turku, Finland
1989-1994, Ilonen laboratory, Immunogenetics, Department of Microbiology, University of Oulu and University of Turku, Finland
1995-1999, Nepom Laboratory (Gerald Nepom, M.D., PH.D.), Virginia Mason Research Center, Benaroya Research Institute, Seattle, WA
2016-present, Associate Professor, Immunology and Theranostics, Diabetes & Metabolism Research Institute, City of Hope, Duarte, CA
2005-2016, Research Assistant Member, Diabetes, Benaroya Research Institute, Seattle, WA
2005-11, Affiliate Assistant Professor, Department of Immunology, University of Washington, Seattle, WA
Research
Laboratory
- Ability to screen for the risk to develop type 1 diabetes and to stage autoimmune process from the first signs of autoimmunity (pre-diabetes) to insulin dependence is important for understanding the natural history of the disease. Understanding the diversity of underlying mechanisms of type 1 diabetes is critical for the need to design individualized therapy approach in the clinical intervention. We are using advanced immunological assays to study the low frequency autoantigen specific CD4 and CD8 T cells. We determine their specificity, phenotypic and gene expression profiles and the functional properties. We expect to discover novel biomarkers and pathways relevant for disease progression which will help us to understand the critical checkpoints in the pathogenesis of type 1 diabetes. Furthermore, understanding the diversity of the immune profile in those who develop type 1 diabetes is important for the stratification of the patients and selection of the appropriate therapeutic approach to intervene the disease progression.
- Modern tools of monitoring the changes in antigen specific T cell repertoire in response to treatment in the clinical trials is a shared long-term interest between researchers at City of Hope. Informative markers, such islet autoantigen specific T cells with disease associated phenotype or the genetic variants, could also contribute to the understanding of mechanistic outcomes of the therapy by relating the observed clinical response to cellular or molecular pathways. Only by confirming these links we can identify causative immune phenotypes in type 1 diabetes, which could become the legitimate targets of drug development. In our studies, we analyze the functional phenotype of newly emerging T cells post-therapy, specifically, whether they recognize pre-existing or new targets and whether the immune profile has changed. It will be important to establish whether the post-immunization response is a result of mobilization and/or clonal expansion of existing autoreactive T cell clonotypes or engagement of naive cells with a different functional phenotype. It is also of ultimate importance to examine why some subjects are different and remain nonresponders to the treatment or are “outliers”. These studies could provide an entirely new perspective on autoimmune disease. We will explore whether there are many available T cells capable of responding to the autoantigen, and why the expansion of these repertoires is not a component of the natural history of the disease.
- One of the most interesting questions in type 1 diabetes etiology is why some gene variants protect from the disease. We are investigating how genetic protection involves peripheral immune regulatory pathways. We expect to discover a regulatory phenotype in healthy individuals, or distinct features retaining differentiation to pathogenic functions. These studies will provide us with a greater insight into the basic understanding of T cell responses in autoimmunity and how they are regulated.
- Our studies on the pancreas and islet transplantation recipients show that recurrence of autoimmunity is possible despite immunosuppression that prevents rejection. The samples collected from the long-term type 1 diabetes patients over time demonstrated persistent memory islet autoantigen specific T cell response. Long-lasting autoreactive memory is an obstacle for the goal of lasting insulin independency in the transplant setting. It can also be the reason why many immunomodulatory therapies fail to have long-lasting effect in recent onset type 1 diabetes, even when initially successful in maintaining the residual beta cell function. Our study will elucidate the importance of understanding the phenotypic profile of the islet autoreactive T cells before the transplantation at “baseline” and how it affects the outcome.
Lab Members
Awards & Memberships
Awards
2000, JDRF Career Development Award, Early career award
1997, The Academy of Finland Medical Council postdoctoral fellowship award
1995, The Academy of Finland Medical Council postdoctoral fellowship award
1994, Paulo Foundation Award, Young investigator award
1993, Novo Nordisk Foundation Award, Ph.D. student fellowship
1993, Wihuri Foundation Award, Young investigator award
1992, Alma and K.A. Snellman Foundation Award, Ph.D. student fellowship
1992, Nordisk Insulin Fond Award, Ph.D. student fellowship
1992, Zonta International Foundation Award, Young female investigator award
1991, University of Oulu graduate student scholarship
1990, Finnish Academy of Science graduate student fellowship
1989, Alma and K.A. Snellman Foundation Award, Ph.D. student fellowship
1989, Finnish Diabetes Foundation fellowship, Ph.D. student fellowship
1988, Aaltonen Foundation fellowship, Ph.D. student fellowship
1988, Alma and K.A. Snellman Foundation Award, Ph.D. student fellowship
Memberships
2012-2016 Diabetes Research Center, University of Washington (affiliate member)
2008-2016 Institute of Translational Health Sciences, WA (investigator)
2006-present, Network for Pancreatic Organ Donors with Diabetes (member and investigator)
2004-2013, NIH/NIDDK TrialNet (investigator, member, mechanistic outcomes committee, ad hoc reviewer)
2003-present, Federation of Clinical Immunology Societies
2000-2010, American Diabetes Association
1995-present, Immunology of Diabetes Society