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
Research Summary: 
cellular and molecular mechanisms that modify immune responses; 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.
Research Detail: 

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.

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.

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.

Selected Publications: 
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
Russ AJ, Wentworth L, Xu K, Rakhmilevich A, Seroogy CM, Sondel PM, Suresh M, Cho CS. Suppression of T-cell expansion by melanoma is exerted on resting cells. Ann Surg Oncol. 2011 Dec;18(13):3848-57. Epub 2011 Apr 5
Verbsky JW, Baker MW, Grossman WJ, Hintermeyer M, Dasu T, Bonacci B, Reddy S, Margolis D, Casper J, Gries M, Desantes K, Hoffman GL, Brokopp CD, Seroogy CM, Routes JM. Newborn screening for severe combined immunodeficiency; the Wisconsin experience (2008-2011). J Clin Immunol. 2012 Feb;32(1):82-8. Epub 2011 Nov 10.
Wernimont SA, Simonson WT, Greer PA, Seroogy CM, Huttenlocher A. Calpain 4 is not necessary for LFA-1-mediated function in CD4+ T cells. PLoS One. 2010 May 7;5(5):e10513.
Singh AM, Evans MD, Gangnon R, Roberg KA, Tisler C, DaSilva D, Pappas T, Salazar L, Gern JE, Lemanske, RF and Seroogy CM. (2010) Expression patterns of atopic eczema and respiratory illnesses in a high-risk birth cohort. Journal of Allergy and Clinical Immunology. Feb; 125(2): 492-493, PMID: 20159261; NIHMSID: NIHMS232583.
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.
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.
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, Singh AM, Dahlberg PE, Nettenstrom L, Seroogy CM (2008). 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, Nov. 25 (Epub).