Biochemistry

Gary A. Weisman

Professor of Biochemistry
Director of Graduate Admissions and Recruitment

E-mail:weismang@missouri.edu

Office: 540E Bond Life Sciences Center

Mail: Biochemistry
540E Bond Life Sciences Center
University of Missouri
Columbia, MO 65211

Phone: 573-882-5005

Fax: 573-884-2537

Lab: 573-882-1708

Educational background

Notable honors and service

• Conference Organization
  • Organizer, ASPET Colloquium on P2 Purinoceptor Structure and Function, 1995
  • Advisory Committee, 3rd International Workshop on Beta-ATPases and Related Ectonucleotidases, 2002
• Editorial Boards
  • Biomedical Research
  • Purinergic Signalling

• Local host of the Annual American Society of Neurochemistry meeting in St. Louis, MO, 2011

Research description

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.

Selected publications

Peterson, T.S., Camden, J., Wang, Y., Seye, C.I., Wood, W.G., Sun, G.Y., Erb, L., and Weisman, G.A. (2010) P2Y₂ Nucleotide Receptors Mediate Inflammatory Responses in the Brain. Mol. Neurobiol. 41:356-366. PMID: 20387013.

Kong, Q., Peterson, T.S., Baker, O.J., Stanley, E., Camden, J.M., Seye, C.I., Erb, L., Wood, W.G., Sun, G.Y., and Weisman, G.A. (2009) Interleukin-1β Enhances Nucleotide-Induced α-Secretase-Dependent Amyloid Precursor Protein Processing in Rat Primary Cortical Neurons Via Up-regulation of the P2Y₂ Receptor. J. Neurochem. 109, 1300-1310. PMCID:  PMC2710802

Camden, J.M., Schrader, A.M., Camden, R.E., González, F.A., Erb, L., Seye, C.I., and Weisman, G.A. (2005) P2Y₂ Nucleotide Receptors Enhance α-Secretase-dependent Amyloid Precursor Protein Processing. J. Biol. Chem. 280:18696-18702

Liao, Z., Seye, C.I., Weisman, G.A., and Erb, L. (2007) The P2Y₂ Nucleotide Receptor Requires Interaction with αV Integrins to Access and Activate G12. J. Cell. Sci. 120:1654-1662

Baker O.J., Camden J.M., Redman R.S., Jones J.E., Seye C.I., Erb L., Weisman G.A. (2008) Proinflammatory cytokines tumor necrosis factor-alpha and interferon-gamma alter tight junction structure and function in the rat parotid gland Par-C10 cell line. Am. J. Physiol., Cell Physiol. 5:C1191-201

Yu N., Erb L., Shivaji R., Weisman G.A., Seye C.I. (2008) Binding of the P2Y₂ nucleotide receptor to filamin A regulates migration of vascular smooth muscle cells. Circ. Res. 5:581-8

Baker OJ. Camden JM. Rome DE. Seye CI. Weisman GA. (2008) P2Y₂ nucleotide receptor activation up-regulates vascular cell adhesion molecule-1 expression and enhances lymphocyte adherence to a human submandibular gland cell line. Mol Immunol. 45(1):65-75

Kong Q. Peterson TS. Baker O. Stanley E. Camden J. Seye CI. Erb L. Simonyi A. Wood WG. Sun GY. Weisman GA. (2009) Interleukin-1beta enhances nucleotide-induced and alpha-secretase-dependent amyloid precursor protein processing in rat primary cortical neurons via up-regulation of the P2Y₂ receptor. J. Neurochem. 109(5):1300-10

Emilie Degagné, Djordje M. Grbic, Andrée-Anne Dupuis, Elise G. Lavoie, Christine Langlois, Nishant Jain, Gary A. Weisman, Jean Sévigny, and Fernand-Pierre Gendron (2009) 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