Gary A. Weisman

Professor of Biochemistry
Director, Graduate Admissions and Recruitment

Email:	weismang@missouri.edu
Phone:	(573) 882-5005
Lab:	(573) 882-1708
Fax:	(573) 884-2537
Office:	540E Bond Life Sciences Center
Mailing Address:	Biochemistry 540E Bond Life Sciences Center University of Missouri-Columbia Columbia, MO 65211
Research Areas:	Nucleotide receptors and signaling in inflammation, cardiovascular and autoimmune exocrine disease.

Educational Background

Notable Honors and Service

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 disorders, including 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

Seye, C.I., Kong, Q., Erb, L., Garrad, R.C., Krugh, B.W., Wang, M., Turner, J.T., Sturek, M., González, F.A., Weisman, G.A. (2002) Functional P2Y₂ Nucleotide Receptors Mediate Uridine 5-Triphosphate Induced Intimal Hyperplasia in Collared Rabbit Carotid Arteries. Circulation 106, 2720-2726

Seye, C.I., Yu, N., Jain, R., Kong, Q., Minor, T., Newton, J., Erb, L., Gonzalez, F.A., and Weisman, G.A. (2003) The P2Y₂ Nucleotide Receptor Mediates UTP-induced Vascular Cell Adhesion Molecule-1 Expression in Coronary Artery Endothelial Cells. J. Biol. Chem. 278, 24960-24965.

Liu, J., Liao, Z., Camden, J., Griffin, K.D., Garrad, R.C., Santiago-Perez, L.I., Gonzalez, F.A., Seye, C.I., Weisman, G.A., and Erb, L. (2004) Src homology 3 Binding Sites in the P2Y₂ Nucleotide Receptor Interact with Src and Regulate Activities of Src, Proline-rich Tyrosine Kinase 2, and Growth Factor Receptors. J. Biol. Chem. 279, 8212-8218.

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.

Bagchi, S., Z. Liao, F.A. Gonzalez, N.E. Chorna, C.I. Seye, G.A. Weisman, L. Erb. 2005. The P2Y₂ nucleotide receptor interacts with α_V integrins to activate G_o and induce cell migration. J. Biol. Chem. 280:39050-7.

Baker, O., Camden, J.M., Schrader-Ratchford, A.M., Seye, C.I., Erb, L., and Weisman, G.A. (2006) Differential Coupling of the P2Y₁ Receptor to Ga₁₄ and Ga_q/11 Proteins During the Development of the Rat Salivary Gland. Arch. Oral Biol. 51, 359-370.

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