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- Gene regulation in the immune system
- T-cell phenotyping in immune conditions
- Biology and pharmacology of human type 2 T cells
Our research has long been devoted to the study of the regulation of transcription of cytokine genes in polarized T cells and in basophils/mast cells. In particular, our laboratory is focused on the identification and pharmacological manipulation of factors uniquely involved in the regulation of the type 2 cytokines, interleukin (IL)-4 and IL-13, at both the transcriptional and epigenetic levels. These include factors of the NF-?B/Rel family, especially p65 and p50, and of the novel family of Grainyhead-related proteins, including LBP-1c/LSF/CP2 and its related proteins, LBP-1a and -1d.
It is the aim of our laboratory to fully elucidate the mechanisms that account for polarized cytokine profiles in effector T helper (Th) cells. Our current studies are testing the central hypothesis that these processes depend to a significant extent on the balance of NF-?B molecular species and the specific interactions of these proteins with other nuclear factors, e.g. Bcl-3 and C/EBP?, and chromatin-modifying agents.
In parallel studies we are assessing the mechanistic and clinical implications of recent studies identifying certain surface molecules as phenotypic and functional determinants of polarized Th cells. Specifically, we have focused on the chemokine receptor, CCR5, and on the structurally related PGD2 receptor, CRTH2, as faithful, selective markers for human Th1 and Th2 cells, respectively. Our studies are aimed at (i) characterizing the phenotypes of cells expressing CCR5 or CRTH2, (ii) understanding the function of either marker in differential regulation of Th-cell gene expression program, and (iii) assessing the prevalence and function of CCR5- and CRTH2-expressing Th cells in immune conditions associated with and possibly caused by imbalanced immune responses, e.g. asthma and systemic sclerosis (scleroderma).
Vincenzo Casolaro, MD, PhD
Associate Professor of Medicine, Division of Allergy & Clinical Immunology
- Casolaro V, Georas SN, Song Z, Zubkoff ID, Abdulkadir SA, Thanos D, Ono SJ. Inhibition of NF-AT-dependent transcription by NF-?B: Implications for differential gene expression in T helper cell subsets. Proc Natl Acad Sci USA 1995; 92:11623-7
- Song Z, Casolaro V, Chen R, Georas SN, Monos D, Ono SJ. Polymorphic nucleotides within the human IL-4 promoter that mediate overexpression of the gene. J Immunol 1996; 156:424-9
- Georas S, Cumberland J, Burke T, Chen R, Schindler U, Casolaro V. Stat6 inhibits interleukin 4 promoter activity in T cells. Blood 1998; 92:4529-38
- Georas S, Cumberland J, Ono S, Casolaro, V. Characterization of a novel negative regulatory element in the human interleukin 4 promoter. Leukemia 2000; 14:629-35
- Casolaro V, Keane-Myers AM, Swendeman SL, Steindler C, Zhong F, Sheffery M, Georas SN, Ono SJ. Identification and characterization of a critical CP2-binding element in the human interleukin-4 promoter. J Biol Chem 2000; 275:36605-11
- Cianferoni A, Schroeder JT, Kim J, Schmidt JW, Lichtenstein LM, Georas SN, Casolaro V. Selective inhibition of IL-4 gene expression in human T cells by aspirin. Blood 2001; 97:1742-9
- Schroeder JT, Miura K, Kim HH, Sin A, Cianferoni A, Casolaro V. Selective expression of nuclear factor of activated T cells (NFAT)-2/c1 in human basophils: evidence for involvement in IgE-mediated IL-4 generation. J Allergy Clin Immunol 2002; 109:507-13
- Keen JC, Cianferoni A, Florio G, Guo J, Chen R, Roman J, Wills-Karp M, Casolaro V, Georas SN. Characterization of a novel PMA-inducible pathway of interleukin-13 gene expression in T cells. Immunology 2006; 119:29-37
- De Fanis U, Mori F, Kurnat RJ, Lee W, Bova M, Adkinson NF, Casolaro V. GATA3 upregulation restricted by surface expression of CD294/CRTH2: a unique feature of human Th cells. Blood 2007; 109:4343-4350
- Boin F, De Fanis U, Bartlett SJ, Wigley FM, Rosen A, Casolaro V. T cell polarization identifies distinct clinical phenotypes in scleroderma lung disease. Arthritis Rheum 2008; 58:1165-1174
- Casolaro V, Fang X, Tancowny B, Fan J, Wu F, Asaki SY, De Fanis U, Huang SK, Gorospe M, Atasoy UX, Stellato C. Posttranscriptional regulation of IL-13 in T cells: role of the RNA-binding protein HuR. J Allergy Clin Immunol 2008; 121:853-859
- De Fanis U, Wang GC, Fedarko NS, Walston JD, Casolaro V, Leng SX. T-lymphocytes expressing CC chemokine receptor-5 and frailty in older adults. J Am Geriatr Soc 2008; 56:904-908
- Sapone A, Lammers KM, Mazzarella G, Mikhailenko I, Cartenì M, Casolaro V, Fasano A. Differential mucosal IL-17 expression in two gliadin-induced disorders: gluten sensitivity and the autoimmune enteropathy celiac disease. Int Arch Allergy Immunol 2009; 152:75-80
- Wang GC, Kao WHL, Murakami P, Xue Q, Chiou RB, Detrick B, McDyer JF, Semba RD, Casolaro V, Walston JD, Fried LP. Cytomegalovirus infection and the risk of mortality and frailty in older women: a prospective observational cohort study. American Journal of Epidemiology 2010; 171:1144-1152.
Last Updated: 7/31/10