University of Nebraska Medical Center

Laboratory of Daniel Monaghan, PhD

Research Goals

  • Development of subtype-selective glutamate receptor antagonists to determine the roles of individual receptors in brain function and brain disorders
  • Determine the intracellular signaling pathways by which NMDA receptors regulate neuronal cell function
  • Evaluation of glutamate receptor regulation of neuronal oscillations using electroencephalography

Techniques used in laboratory

  • Molecular biology (construction of cDNA point mutations and chimeras, PCR, cRNA synthesis, yeast two-hybrid)
  • Neuroanatomy and neuropharmacology (quantitative receptor autoradiography, in situ hybridization, immunohistochemistry, radioligand binding)
  • Protein chemistry (immunoprecipitation, Western blotting, protein phosphorylation, two dimensional peptide mapping)
  • Electrophysiology (two electrode voltage clamp of frog oocytes; hippocampal extracellular recordings, patch-clamp of brain cells in hippocampal slices, dynamic calcium imaging)
  • Cell culture (primary cells and brain tissue slice cultures)
  • Molecular modeling (homology receptor modeling and drug-receptor docking)


Development and Pharmacology of Positive Allosteric Modulators of NMDA Receptors

PI: D. Monaghan

Source: NIH/NIMH 4R01 MH060252

The grant Development and Pharmacology of Positive Allosteric Modulators of NMDA Receptors supports the development of novel NMDA receptor antagonists that are designed to block the function of distinct subtypes of NMDA receptors. The projects uses a combination of medicinal chemistry, molecular modeling, molecular biology, and electrophysiology to design, make and test new compounds that may be of use in treating Alzheimer's, Huntington's, Parkinsons disease as well as stroke, schizophrenia, and neuropathic pain.

Glutamate Delat-1 Receptor and Metabotropic Glutamate Receptor Interaction

PI: S. Dravid; C-I: D. Monaghan

Source: National Science Foundation NSF1456818

The objective of this grant is to characterize the protein-protein interactions between Delta-1 receptors and metabotropic glutamate receptors and their effects on receptor signaling.

NMDA receptor subtypes in basal ganglia

Co-I: D. Monaghan

Source: Subcontract with Creighton University

The Molecular Biology of Neurosensory Systems

PI: S. Smith; Co-I: D. Monaghan

The goal of this project is to develop a conditional mouse model to study the role of Nr2e3 in adult cone and rod photoreceptors and to identify genetic and direct interacting factors that work with Nr2e3 to influence photoreceptor cell development.