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Research Interests
- Gene regulation in the immune system
- Pharmacologic regulation of T-cell effector functions
Past Research
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 Th2 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.
Current Research
It is the aim of our laboratory to fully elucidate the mechanisms that account for polarized cytokine profiles in effector T helper cells. Our current studies are testing the central hypothesis that these processes depend to a large extent on the expression and function of LBP-1c/LSF/CP2, the balance of NF-?B molecular species, and the specific interactions of these proteins with other transcription factors, e.g. Yin Yang-1 and Bcl-3, and chromatin-modifying agents. Given the recognition of NF-?B and LBP-1c as effectors of the pathways conferring resistance to oxidative insults and apoptosis, parallel studies will be conducted to assess the regulation of these processes concomitant with the activation of T helper cell polarized responses.
Laboratory
Principal investigator:
Vincenzo Casolaro, MD, PhD
Assistant Professor of Medicine, Division of Allergy & Clinical Immunology
Post-doctoral fellow(s):
Umberto De Fanis, MD
Technician(s):
Rebecca Jeanne Kurnat, BS
Won Kyung Lee, MS
Positions available
None
Selected Publications
- 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
- Kim J, Sanders SP, Siekierski ES, Casolaro V, Proud D. Role of NF-?B in cytokine production induced from human airway epithelial cells by rhinovirus infection. J Immunol 2000; 165:3384-92
- 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
- Barnes KC, Mathias RA, Nickel R, Freidhoff LR, Stockton ML, Xue X, Naidu RP, Levett PN, Casolaro V, Beaty TH. Testing for gene-gene interaction controlling total IgE in families from Barbados: Evidence of sensitivity regarding linkage heterogeneity among families. Genomics 2001; 71:246-51
- 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
- Vonakis BM, Sora R, Langdon JM, Casolaro V, MacDonald SM. Inhibition of cytokine gene transcription by the human recombinant histamine releasing factor (HrHRF) in human T lymphocytes. J Immunol 2003; 171:3742-50
Last Updated: 3/31/06
