Dianne Perez, PhD
My early publications were seminal in the alpha1-adrenergic receptor (alpha1-AR) field, starting with cloning the receptors, determining the correct nomenclature based upon pharmacology, and initially characterizing their signal transduction pathways. After the initial characterization of the alpha1-ARs, I next mapped out the ligand-binding pocket for both agonists, antagonists, and specialized ligands called imidazolines. This collection of work was very useful to the pharmaceutical industry during the 1990s and 2000s, as several drugs were synthesized based upon my structure-function studies to treat conditions such as stress urinary incontinence and benign prostatic hyperplasia. And now the same approach may be useful to treat neurological disorders. My studies were also seminal for providing insight into how these receptors are activated, by showing the specific amino acid residues involved in the activation process, and the discovery of constitutive activity. Several of these amino acid residues have been shown subsequently to be involved in similar mechanisms in other G-protein-coupled receptors. After the structure-function studies, we created unique transgenic mouse models using large fragments of the isogenic promoters to over express wild type and constitutively active alpha1-AR subtypes in all natively expressing tissues. These mouse models are state of the art in the ability to express and characterize subtype-selective signaling and revealed novel physiology and pathophysiology never before associated with these receptors.