Tonio Pera, PhD

Assistant Professor
Department of Medicine, Division of Pulmonary, Allergy & Critical Care Medicine

American Thoracic Society

Applying novel GPCR biology and pharmacology to diseases involving smooth muscle dysfunction. G protein-coupled receptors (GPCRs) are the largest protein family in the human genome and the majority of most prescribed drugs target GPCRs.  The work in Dr. Pera’s lab combines expertise in physiology and pharmacology with GPCR biology and biochemistry with the goal of identifying GPCR ligands which exploit novel signaling mechanisms to manage smooth muscle function and thereby treat cardiovascular and lung diseases. Drug development for cardiovascular and lung diseases has focused largely on refinement within the existing classes of drugs and on the use of combinations of these drugs. This strategy has led to improvements in disease management, but as various classes of drugs have reached their full potential this strategy will yield diminishing returns. The concept of biased agonism that has emerged recently indicates that certain ligands of GPCRs may not only turn receptors on or off but also induce qualitatively distinct signaling by the receptors. Our research aims to utilize this novel concept of biased agonism to fine-tune receptor signaling so as to eliminate detrimental, and promote beneficial, signaling in the pulmonary and vascular systems. Specifically, our current work involves: 1) identifying arrestin-biased muscarinic ligands and delineating muscarinic arrestin signaling in airway smooth muscle with the goals of treating asthma and COPD; and 2) targeting specific eicosanoid receptors (EP prostaglandin, cysteinyl leukotriene) with novel subtype selective or biased ligands to manage excessive vascular smooth muscle growth that contributes to hypertension, heart attacks, and stroke.