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|Chris Seroogy, MD|
Research SummaryBiological role of a novel E3 ubiquitin ligase called GRAIL in T cell function; hematopoietic tissue development
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.
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.
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.
Friedlander S, Dooms K, Voss C, Agger W, Zhang K, Bleesing J, Filipovich A, Seroogy CM (2008). Adolescent Presentation of X-linked Lymphoproliferative Disease. Annals of Allergy, Asthma & Immunology 100(4): 398-400.
Lineberry N, Su L, Lin J, Coffey G, Seroogy CM, Fathman CG (2008). Cutting Edge: The Transmembrane E3 Ligase GRAIL Ubiquitinates CD40L During the Induction of T Cell Anergy. Journal of Immunology 181(3): 1622-6.
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).
Simonson WT, Markovina S, Grossman WJ, Lokuta MA, Doan AT, Seroogy CM, Huttenlocher A (2008). Common variable immunodeficiency with regulatory T cell deficiency treated with rapamycin. Annals of Allergy, Asthma & Immunology, accepted.
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File last updated: August 1, 2012