Faculty Profile:

Sergei Atamas, M.D., Ph.D.
Associate Professor

Department of Microbiology and Immunology Department of Medicine
School of Medicine

410-605-7000 x6468 or 410-706-6474

satamas@umaryland.edu

Research

The goal of our research is to understand the complexity of immune and inflammatory signals that drive tissue fibrosis, particularly pulmonary fibrosis. This debilitating and often fatal condition develops in patients with such diseases as scleroderma, idiopathic pulmonary fibrosis, rheumatoid arthritis, graft-versus-host disease after bone marrow and organ transplantation, occupational inhalation of dust particles, and post radiation- and chemotherapy. Numerous studies, including our own, suggest that tissue fibrosis, including fibroblast proliferation and collagen production, is regulated by a complex and redundant network of profibrotic factors. We focus on cytokines (TGF-beta, IL-14, IL-13, Oncostatin M), chemokines (MCP-1, PARC), and cell surface molecules (CD40L) that are produced by the immune and inflammatory cells, specifically T cells and macrophages, and drive fibroblast proliferation and collagen production. Remarkably, elimination of only one of these cytokines or their receptors may completely prevent development of fibrosis in animal models, suggesting that despite the complexity of its regulatory mechanisms, fibrosis is a highly integrated process. Targeting the members of the profibrotic regulatory network may become a viable therapeutic option. We are investigating expression patterns of the profibrotic factors by T cells and macrophages, and intracellular signaling in fibroblasts initiated by these factors, in order to better characterize suitable potential molecular targets for future antifibrotic therapies.

Publications

Atamas SP, Choi J, Yurovsky VV, White B. An alternative splice variant of human interleukin-4, IL-4d2, inhibits interleukin-4 stimulated T cell proliferation. J Immunol 1996, 156:435-441

Atamas SP. Self-organization in computer-simulated selective systems. BioSystems 1996, 39:143-151

Alms WJ, Atamas SP, Yurovsky VV, White B. Generation of a variant of human interleukin-4 by alternative splicing. Molec Immunol 1996, 33:361-370

Tsytsikov VN, Yurovsky VV, Atamas SP, Alms WJ, White B. Identification and characterization of two alternative splice variants of human interleukin-2. J Biol Chem 1996, 271:23055-23060

Atamas SP, Yurovsky VV, Wise R, Wigley FM, Goter Robinson CJ, Henry P, Alms WJ, White B. Production of type 2 cytokines by CD8+ lung cells is associated with greater decline in pulmonary function in patients with systemic sclerosis. Arthritis Rheum 1999, 42:1168-1178

Luzina IG, Knitzer RH, Atamas SP, Gause WC, Papadimitriou JC, Sztein MB, Storrer CE, Handwerger BS. Vasculitis in the Palmerson North (PN) mouse model of lupus: phenotype and cytokine production profile of infiltrating cells. Arthritis Rheum 1999, 42:561-568

Arinobu Y, Atamas SP, Otsuka T, Niiro H, Yamaoka K, Mitsuyasu H, Niho Y, Hamasaki N, White B, Izuhara K. Antagonistic effects of an alternative splice variant of human IL-4, IL-4d2, on IL-4 activities in human monocytes and B cells. Cell Immunol 1999, 191:161-167

Henry PA, Atamas SP, Yurovsky VV, Luzina IG, Wigley FM, White B. Diversity and plasticity of the anti-DNA topoisomerase I autoantibody response in scleroderma. Arthritis Rheum 2000, 43:2733-2742

Luzina IG, Atamas SP, Storrer CE, daSilva LC, Kelsoe G, Papadimitriou JC, Handwerger BS. Spontaneous Formation of Germinal Centers in Autoimmune Mice. J Leukoc Biol 2001, 70:578-584

Atamas SP, Luzina IG, Dai H, Wilt SG, White B. Synergy between CD40 ligation and IL-4 on fibroblast proliferation involves IL-4 receptor signaling. J Immunol 2002, 168:1139-1145

Rus V, Atamas SP*, Shustova V, Luzina IG, Selaru F, Magder LS, Via CS. Expression of Cytokine and Chemokine-Related Genes in Peripheral Blood Mononuclear Cells from Lupus Patients by cDNA Array. *First two authors contributed equally to this work. Clin Immunol 2002, 102:283-290

Luzina IG, Atamas SP*, Wise R, Wigley FM, White B. Gene expression in bronchoalveolar lavage cells from scleroderma patients. *First two authors contributed equally to this work. Am J Respir Cell Mol Biol 2002, 26:549-557

Luzina IG, Atamas SP*, Wise R, Wigley FM, Choi J, Xiao HQ, White B. Occurrence of an activated, profibrotic pattern of gene expression in lung CD8+ T cells from scleroderma patients. *First two authors contributed equally to this work. Arthritis Rheum 2003, 48:2262-2274

Atamas SP, Luzina IG, Choi J, Tsymbalyuk N, Carbonetti N, Singh IS, Trojanowska M, Jimenez SA, White B. Pulmonary and activation-regulated chemokine stimulates collagen production in lung fibroblasts. Am J Respir Cell Mol Biol 2003, 29:743-749

Atamas SP. Hasard et Dégénérescence (Chance and Degeneracy). Sci Avenir (France) 2003, No136:34-38

Atamas SP, White B. Cytokine regulation of pulmonary fibrosis in scleroderma. Cytokine Growth Factor Rev 2003, 14:537-550

Atamas SP. Les affinités électives. Pour la Science (France) 2005, N° 46:39-43

Luzina IG, Tsymbalyuk N, Choi J, Hasday JD, Atamas SP. CCL18-Stimulated upregulation of collagen production in lung fibroblasts requires Sp1 signaling and basal Smad3 activity. J Cell Physiol 2006, 206:221-228

Fishelevich R, Malanina A, Luzina I, Atamas S, Smyth MJ, Porcelli SA, Gaspari AA. Ceramide-dependent regulation of human epidermal keratinocyte CD1d expression during terminal differentiation. J Immunol. 2006, 176:2590-9

Luzina IG, Papadimitriou JC, Anderson R, Pochetuhen K, Atamas SP. Adenoviral gene transfer of CCL18 in the lung induces prolonged infiltration of T lymphocytes and transient T lymphocyte-dependent collagen deposition. Arthritis Rheum 2006, In Press

Viscardi RM, Atamas SP, Luzina IG, Hasday JD, He JR, Sime PJ, Coalson JJ, Yoder BA. Antenatal Ureaplasma urealyticum respiratory tract infection stimulates pro-inflammatory, pro-fibrotic responses in the preterm baboon lung. Pediatr Res 2006, In Press

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