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Office: (859) 323-5131
Fax: (859) 257-8994
Lab: (859) 323-5914
Email: dcohen@uky.edu
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Donald A. Cohen, Ph.D.
Professor
Doctoral Studies: University of Cincinnati.
Postdoctoral: Medical College of Virginia.
Research Statement:
Inflammation in various organs can be caused by a variety of factors, including infectious agents, autoimmunity, environmental pollutants and therapeutic modalities. Regardless of the cause, the failure to adequately regulate the inflammatory response can lead to persistent inflammation and the development of structural changes in tissue architecture that can affect normal function in the inflamed tissue. Research in this laboratory is focused on understanding immunological mechanisms which regulate the onset and persistence of inflammation in acute and chronic disease settings.
The primary focus of the lab evaluates the contribution of innate immune cells to the development of experimental colitis. Inflammatory bowel disease (IBD) is a severe chronic inflammation of the intestinal tract that affects over 1.4 million people in the U.S. The precise roles of individual types of immune cells in the development of IBD remain unresolved, including the role of macrophages and dendritic cells. Macrophages play multiple roles during an inflammatory response. First, macrophages present in the tissue are involved in initiating an inflammatory response by engulfing inflammatory stimuli and then releasing factors which call in additional immune cells to the tissue site. Secondly, additional macrophages arrive at the tissue site from the blood, thus amplifying inflammation. Finally, when the inflammatory stimulus is removed, macrophages then release a variety of factors that aid in the healing process in the injured tissue. Dendritic cells are critical for initiating specific immune responses against foreign antigens and their functional state determines the most appropriate type of immune response to efficiently eliminate infecting microorganisms. Under normal conditions in the intestinal tract, both macrophages and dendritic cells inhibit inflammation and immune responses to prevent reactions against ingested food antigens and normal intestinal microbes. However, this control is lost during IBD leading to chronic intestinal inflammation. We have demonstrated that both macrophages and dendritic cells play a protective role in preventing colitis and are identifying genes which control these protective functions. Understanding the mechanisms by which these innate immune cells regulate intestinal inflammation will allow identification of new potential therapeutic target in patients with inflammatory bowel disease.
Selected Recent Publications:
Arsenescu V, Narasimhan ML, Halide T, Bressan RA, Barisione C, Cohen DA, de Villiers WJ, Arsenescu R. Adiponectin and plant-derived Mammalian adiponectin homolog exert a protective effect in murine colitis. Dig Dis Sci. 2011 Oct;56(10):2818-32. PMID:21479819. [Abstract]
Zeng L, O’Connor C, Zhang J, Kaplan AM and DA Cohen. IL-10 Promotes Resistance to Apoptosis and Metastatic Potential in Lung Tumor Cell Lines. Cytokine. 49: 294-302, 2010. PMID:20034810. [Abstract]
Dasu T, Qualls JE, Tuna H, Raman C, Cohen DA, Bondada S. CD5 plays an inhibitory role in the suppressive function of murine CD4+ CD25+ Treg cells. Immunology Letters 119(1-2):103-13, 2008. PMID: 18573278. [Abstract]
Qualls J, , Tuna H, Kaplan AM, and Cohen DA. Suppression of experimental colitis in mice by CD11c+ dendritic cells. Inflamm Bowel Dis. 15(2):236-47, 2009. PMID:18839426. [Abstract]
Jose P, Kaplan AM, and DA Cohen. Inhibition of IL-10 signaling in lung dendritic cells by TLR4 ligands. Exp Lung Res. 35(1):1-28, 2009. PMID:19191102. [Abstract]
Qualls J, Kaplan AM, and Cohen DA. Qualls J, Kaplan AM, and Cohen DA. Suppression of Experimental Colitis by Intestinal Mononuclear Phagocytes. J Leukoc Biol 80: 802-815, 2006. [Abstract]
Hongo, D, Bryson J.S., Kaplan A.M. and D.A. Cohen. Endogenous nitric oxide protects against T cell-dependent lethality during graft-vs-host disease and idiopathic pneumonia syndrome. J. Immunol. 173: 1744-1756, 2004 [Abstract]
Fernandez, S., A.M. Kaplan, and D.A. Cohen. Inhibition of IL-10 receptor function in the lung by toll-like receptor agonists. J. Immunol. 172: 2613 - 2620, 2004 [Abstract]
Burnett, S, Kerschen, EJ, Zhang J., Zeng, L., Straley, SC, A. M. Kaplan and D. A. Cohen. Conditional macrophage ablation in transgenic mice expressing a Fas-based suicide gene. J. Leuk. Biol., 75: 612-623, 2004 [Abstract] |
