Chris Seroogy, MD

Portrait of Chris Seroogy, MD
Associate Professor
Pediatrics
Address: 
4139 WIMR
1111 Highland Ave
Madison, WI 53705
Telephone: 
(608) 263-2652
Focus Groups: 
Immunology/Immunopathology
Education: 
M.D. University of Minnesota
B.S. University of Wisconsin
Research Summary: 
My research laboratory has had a longstanding interest in the cellular and molecular mechanisms that modify immune responses. My work involves utilization of numerous murine models of T cell unresponsiveness and functional analysis of peripheral blood mononuclear cells from human subjects with a particular interest in allergic inflammation and the contexts that lead to its development. Inspired by our observations that T regulatory (Treg) cells are important during in vivo T cell unresponsiveness in murine models, we turned to human disease states that are the result of imbalanced T cell responses. Our study population is infants and children since the foundation for allergic disease is established early in life.
Research Detail: 

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. Treg cells develop in the thymus (naturally occurring) or in lymphoid tissue (induced).  Ongoing work in my laboratory has demonstrated a link between GRAIL (RNF128), an anergy-related E3 ubiquitin ligase, and CD25+ Treg cells. We hypothesize that GRAIL is necessary for the optimal function of naturally occurring and induced CD25+ Treg cells. My laboratory has recently developed a novel conditional knockout mouse model to assist with characterizing the role of GRAIL in Treg cell biology and various immune responses. 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. This line of investigation is amenable to a graduate student PhD thesis project and grant funding is currently being sought.

A second line of investigation in my laboratory involves translational research with infants that are protected from developing allergic disease secondary to unique, but poorly defined environmental exposures. Farming environments have been found to be protective against the development of allergic diseases on multiple continents and include epidemiologic findings from the dairy farming region of Wisconsin. Allergic diseases are major public health problems in children and adults and are initiated in early childhood by poorly understood mechanisms that include alterations in immune maturation and association with severe viral respiratory infections. Mouse models of allergic disease strongly implicate a role for CD25+ Treg cells in initiation, perpetuation and regulation of allergic inflammation. Accumulating published data demonstrates critical interactions between the adaptive and innate immune system impact the development of allergic sensitization and clearance of common respiratory viral infections. The goals of our currently funded study are focused on in-depth investigations to better define the immunologic and environmental profiles at the inception of allergic diseases. Two aims of this study seek to interrogate innate immune cell function using an innovative and sensitive approach optimized in my research laboratory along with cutting-edge techniques to quantify Treg cell function. Results from this study will lead to a better understanding of the impact of farming environments on immune maturation and immune responses that protect against the development of allergic disease and significant respiratory viral infections. The long-term goal is to bring the farm "protective" factors to all infants in a primary prevention manner that would promote healthy immune maturation and overall improved health. This project is NIH funded.

Current Projects

  1. To elucidate the role of GRAIL in CD25+ Treg cell biological function
  2. To prospectively study the adaptive and innate immune maturation in a dairy farming birth cohort with demonstrated protection from allergic disease development and severe respiratory illnesses.

Laboratory Techniques

  1. Multi-parameter flow Cytometry
  2. Real-time QPCR
  3. Retroviral and lentiviral production
  4. Animal models of in vivo tolerance
  5. CD25+ T regulatory cell functional assays (human and rodent)
Selected Publications: 
Anandasabapathy N, Ford GS, Bloom D, Holness C, Seroogy C, Skrenta H, Paragas V, Fathman CG, Soares L (2003). GRAIL: A Novel E3 Ubiquitin Ligase that Inhibits Cytokine Gene Transcription is Expressed in Anergic CD4+ T Cells. Immunity, 18: 1-20.
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.
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.
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, PMID: 17490400; PMCID: PMC1941959.
Schartner JM, Singh AM, Dahlberg PE, Nettenstrom L, Seroogy CM (2009). Recurrent 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, PMID: 19040605; PMCID: PMC2675267.
MacKenzie DA, Seroogy CM (2009) Sustained expression of GRAIL during hematopoiesis results in dysregulated differentiation. Acta Haematologica 122: 230-237, PMID: 19887782; PMCID: PMC189438.
Schartner JM, William T. Simonson, Sarah A. Wernimont, Lauren M. Nettenstrom, Anna Huttenlocher, Seroogy, CM. (2009) Gene Related to Anergy in Lymphocytes (GRAIL) Expression in CD4+ T Cells Impairs Actin Cytoskeletal Organization During T Cell: Antigen Presenting Cell Interactions. Journal of Biological Chemistry, Dec 11;284(50):34674-81, PMID: 19833735; PMCID: PMC2787330.
Nettenstrom L, Alderson K, Raschke EE , Evans MD, Sondel PM, Olek S, Seroogy CM (2013) An Optimized Multi-parameter Flow Cytometry Protocol for Human T Regulatory Cell Analysis on Fresh and Viably Frozen Cells, Correlation with Epigenetic Analysis, and Comparison of Cord and Adult Blood. Journal of Immunological Methods 387 (2013), pp. 81-88, PMID: 23058673.
Singh AM, Dahlberg P, Burmeister K, Evans M, Gangnon R, Roberg KA, Tisler C, DaSilva D, Pappas T, Salazar L, Lemanske RF, Gern JE, Seroogy CM (2013) Inhaled Corticosteroid Use is Associated with Increased Circulating T regulatory Cells in Children with Asthma. Clin Mol Allergy. 2013 Jan 25;11(1):1. [Epub ahead of print] PMID: 23347774