Office: 540E Bond Life Sciences Center
540E Bond Life Sciences Center
University of Missouri
Columbia, MO 65211
|BS||Polytechnic Institute of Brooklyn||Brooklyn, N.Y.||Chemistry/Premedicine|
|PhD||University of Nebraska||Lincoln, Neb.||Chemistry|
Nucleotide receptors (P2 receptors) are present in nearly all cells and tissues where they mediate diverse functions including the regulation of platelet aggregation, muscle contraction, neurotransmission, insulin secretion, epithelial ion transport, wound healing and cell growth. We have isolated the first human P2 receptor gene and expressed it in mammalian cell lines that normally lack this receptor. These expression systems have enabled us to identify and purify the P2 receptor protein and current research is directed towards investigating structural features of the receptor that affect its functions. We have cloned or obtained 11 different P2 receptor subtypes belonging to 2 different receptor superfamilies and we are investigating the mechanisms of receptor activation, desensitization, and signal transduction in a variety of tissues in relation to normal physiological functions and disease.
We have undertaken efforts to determine the molecular mechanisms whereby activation of P2 receptors can be employed for the treatment of human disease. Studies are directed towards: 1) determining the intracellular pathways that enable P2 receptors to promote chloride secretion in cystic fibrosis (CF) epithelium to effectively bypass the genetic defect in chloride transport that underlies CF; 2) investigating the integrin-like properties of P2 receptors in the cardiovascular system in relation to the effects of extracellular nucleotides on platelet aggregation, vasorelaxation and contraction, atherogenesis and inflammatory responses mediated by monocyte adherence to endothelium, responses that are associated with the early stages of atherosclerosis and diabetes; 3) understanding the role of P2 receptors in neuronal apoptosis and reactive astrogliosis associated with Alzheimer's and other neurodegenerative diseases; 4) determining the role of nucleotide receptors in salivary gland inflammation and regeneration to design better treatments for Sjögren's syndrome; and 5) identifying the molecular mechanisms whereby dietary nutriceuticals prevent disease. Our laboratory possesses the relevant molecular reagents and cell systems needed to progress these projects and participating graduate students gain experience in a variety of techniques in molecular and cell biology.
Peterson TS, Thebeau CN, Ajit D, Camden JM, Woods LT, Gibson Wood W, Petris MJ, Sun GY, Erb L, Weisman GA. P2Y2 Nucleotide Receptor Upregulation and Activation Mediates Neurite Extension in IL-1β-treated Mouse Primary Cortical Neurons. J Neurochem. 2013 Mar 30. doi: 10.1111/jnc.12252.
Weisman GA, Woods LT, Erb L, Seye CI. P2Y receptors in the mammalian nervous system: pharmacology, ligands and therapeutic potential. CNS Neurol Disord Drug Targets. 2012 Sep;11(6):722-38.
Woods LT, Camden JM, Batek JM, Petris MJ, Erb L, Weisman GA. P2X7 receptor activation induces inflammatory responses in salivary gland epithelium. Am J Physiol Cell Physiol. 2012 Oct 1;303(7):C790-801. doi: 10.1152/ajpcell.00072.2012. Epub 2012 Aug 8.
Peterson, T.S., Camden, J., Wang, Y., Seye, C.I., Wood, W.G., Sun, G.Y., Erb, L., and Weisman, G.A. P2Y2 Nucleotide Receptors Mediate Inflammatory Responses in the Brain. Mol. Neurobiol. 41:356-366. PMID: 20387013 (2010).Emilie Degagné, Djordje M. Grbic, Andrée-Anne Dupuis, Elise G. Lavoie, Christine Langlois, Nishant Jain, Gary A. Weisman, Jean Sévigny, and Fernand-Pierre Gendron. P2Y2 Receptor Transcription Is Increased by NF-κB and Stimulates Cyclooxygenase-2 Expression and PGE2 Released by Intestinal Epithelial Cells J. Immunol. 183:4521-4529 (2009).