Christine M. Seroogy, MD
Assistant Professor
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Contact the Group
(608) 265-6366
UW Hospital
600 Highland Ave - H4/474
Madison, WI 53792-4108
Seroogy Laboratory
Major Research Interests
My laboratory has been interested in understanding the immunologic contexts that lead to CD4+ T cell unresponsiveness or anergy. During these investigations, we have found that a major operational mechanism of cellular immune unresponsiveness involves a T cell with suppressive capabilities. This T cell was formally identified in the early 1990s and has been termed a CD25+ T regulatory (Treg) cell.
CD25+ T regulatory Cell
Ongoing work in my laboratory has demonstrated a link between GRAIL, an anergy-related E3 ubiquitin ligase, and CD25+ Treg cells. CD25+ Treg cells are a subset of regulatory T cells with an anergic phenotype that suppress immune responses in an antigen-specific fashion by a poorly understood mechanism. We hypothesize that GRAIL is necessary for the optimal function of naturally occurring and induced CD25+ Treg cells. By understanding the molecular basis for suppressor function of CD25+ Treg cells, directed approaches can be developed for therapeutic alternatives to varied disease states that result from inappropriate adaptive immune responses.
A second line of investigation in my laboratory involves translational research with subjects that have allergic diseases. Allergic diseases are major public health problems in children and adults. Allergic diseases are initiated in early childhood by poorly understood mechanisms. Mouse models of allergic disease strongly implicate a role for CD25+ Treg cells in initiation, perpetuation and regulation of allergic inflammation. In contrast, studies in humans with allergic disease are limited. Investigations in the role of CD25+ Treg cells in allergic disease will improve our understanding of allergic inflammation and potentially lead to improved approaches to disease management and treatment.
Current Projects
- To elucidate the role of GRAIL in CD25+ Treg cell biological function.
- To characterize the expression of TLRs on naturally occurring and adaptive CD25+ Treg cells and investigate the effect of their engagement on CD25+ Treg cell biological function.
- To prospectively study the development and function of CD25+ Treg cells in a childhood cohort at increased risk for developing atopic disease.
Laboratory Techniques
- Flow Cytometry
- Real-time QPCR
- Cell Culture
- Retroviral and lentiviral production
- Animal models of in vivo tolerance
- CD25+ T regulatory cell functional assays (human and rodent)
- Confocal microscopy
Staff
 Paul E. Dahlberg, MD Fellow |  Lauren M. Nettenstrom Associate Research Specialist | Jill M. Schartner Research Assistant |  Anne Marie Singh, MD Clinical Instructor | Paul D. Winograd Research Assistant |
Honors & Awards
| Research Trust Junior Faculty Development Award American Academy of Allergy, Asthma & Immunology (AAAAI) |
2007 |
| Medical Education and Research Committee Research Award University of Wisconsin |
2006 |
| R21 Exploratory/Development Research Award NIH/NIAID |
2005 |
| Schering-Plough Junior Faculty Award American Academy of Allergy, Asthma & Immunology (AAAAI) |
2005 |
| Women in Science & Engineering Leadership Institute Grant University of Wisconsin |
2005 |
| Odell Research Award University of Wisconsin |
2004 |
| Midwest Athletes Against Childhood Cancer Fund Award | 2004-09 |
| Howard Hughes Medical Institute Start-up funds | 2004 |
| K08 Career Development Award NIH/NIAID |
2000 |
| Physician Scientist Development Award American College of Rheumatology |
1998 |
Selected Publications
Seroogy CM, Fathman CG (2003) T cell anergy from phenotype to genotype and back. Immunologic Research, 28(3): 255-64.
Soares L, Seroogy CM, Skrenta H, Anandasabapathy N, Lovelace P, Chung CD, Engleman E, Fathman CG (2004) Two isoforms of otubain 1 regulate T cell anergy via GRAIL. Nature Immunology, 5(1): 45-54.
Seroogy CM, Soares L, Ranheim EA, Su L, Holness C, Bloom D, Fathman CG (2004) GRAIL, an E3 ubiquitin ligase, is necessary for the induction of anergy in CD4+ T cells. Journal of Immunology, 173(1): 79-85.
Seroogy CM and Gern JE (2005) The Role of T Regulatory Cells in Asthma. Journal of Allergy and Clinical Immunology, 116(5): 996-9.
MacKenzie DA, Schartner J, Lin J, Timmel A, Jennens-Clough M, Fathman CG, Seroogy CM (2007) GRAIL is Upregulated in CD4+CD25+ T Regulatory Cells and is Sufficient for Conversion of T Cells to a Regulatory Phenotype. Journal of Biological Chemistry, 282(13): 9696-9702.
Schartner J, Fathman CG, Seroogy CM (2007) Preservation of Self: An Overview of E3 Ubiquitin Ligases and T Cell Tolerance. Seminars in Immunology, 19 (3): 188-96.
Jartti T, Burmeister K, Seroogy CM, Jennens-Clough ML, Tisler C, Pleiss L, Evans M, Vrtis R, Wallace P, Ruiz B, Gangnon R, Lemanske RF, and Gern JE (2007) Association between CD4+CD25high T Cells and Atopy in Children. Journal of Allergy and Clinical Immunology, 120 (1): 177-83.
Dahlberg, PE, Schartner, JM, Timmel, A, Seroogy, CM (2007) Daily Subcutaneous Injections of Peptide Induce CD4+ CD25+ T Regulatory Cells. Clinical and Experimental Immunology, 149 (2): 226-34.
Schartner JM, Singh AM, Dahlberg PE, Nettenstrom L, Seroogy CM (2009) Superantigen Exposure In Vivo Leads to Highly Suppressive CD4+CD25+ and CD4+CD25- T Cells with Anergic and Suppressive Genetic Signatures. Clinical and Experimental Immunology, 155(2): 348-56.