Detailed pharmacologic knowledge stands alone as a basic science, but successful therapeutics requires application of this body of scientific information to disease-induced abnormalities in individual patients. For this reason our basic science teaching of pharmacology is complemented with teaching that integrates physiology, pathophysiology, and pharmacology in the context of common major diseases. This constitutes what is considered to be active clinical pharmacology. This strategy allows the demonstration of common principles applicable many diseases . The underlying principle herein is that the pathophysiology of disease and the basic facts of pharmacology must be interdigitated in order to select drugs and establish therapeutic objectives. The basic principles of pharmacology are combined with specific factors of disease and drug such that the dynamics of pharmacology and pathophysiology can be put into the perspective of rational drugs use or therapeutics.
The immune system is a composite of the means by which individual organisms maintain their individual integrity in the face of constant interaction with the environment and the continuous internal process of death and removal of host cells that allows for replacement and growth. Both the innate and adaptive divisions of the immune system are critical to the maintenance of homeostasis, physical integrity, and health. Intricately interactive pathways of cells, cell surface receptors, antibodies, and cytokines provide surveillance against invasive pathogens and nonself entities and internal destruction and removal of host senescent cells. The specificity and efficacy of these immune components interacting with their respective ligands provide the mechanistic basis of immune function. Several disease conditions occur upon immune dysfunction including immune deficiency, allergy, and autoimmunity. Chronic immune system activation accompanies essentially all of the myriad of chronic inflammatory diseases that currently plague our species with the manner and degree of immune contribution to these conditions a current area of intense interest and investigation by the biomedical community.
Understanding the mechanisms by which the immune system works opens many possibilities for investigations within pharmacology. Objectives are principally three-fold: (a) to enhance function in the face of insufficient immune response, (b) to redirect immune processes that themselves may lead to host dysfunction, and (c) to exploit and/or attempt to mimic the exquisite specificity and mobilizing functions of immune responses in drug development.
Immunopharmacology investigators interact extensively with the UA Sarver Heart Center and the Arizona Respiratory Center and are involved in identifying immune mechanisms in chronic inflammatory diseases with special emphasis on those affecting the heart and the lungs. Laboratory based approaches vary from genetic epidemiology, through animal modeling, tissue modeling, ex vivo and in vitro cell biology, to molecular biology. Collaborations also involve translational investigations of evidence-based therapeutic approaches including clinical trials, thus forming bench to bedside and bedside to bench conduits.
Pharmacology as a science is critical to the development of new drugs and therapies for human disease. A drug may be defined as any chemical that affects biological processes. Early pharmacologists studied natural substances, mainly plant extracts such as morphine from the opium poppy, quinine from the bark of the cinchona tree and digitalis from Foxglove. Later in the 19th century pharmacology developed as a biomedical science that applied the principles of scientific experimentation to therapeutic context. Today, the Molelcular and Biochemical Pharmacology group at the University of Arizona use methods of biochemistry, molecular biology, structural biology, cell biology, and cell physiology to define the mechanisms of drug action and how drugs influence the organism by studies on intact animals, organs, cells, sub-cellular compartments and individual protein molecules. Drugs are also used as probes to discover new information about biosynthetic and cell signaling pathways and their kinetics. Ultimately these investigations will reveal how drugs can correct the biochemical abnormalities that are responsible for human illness, thus enabling the elucidation of pathophysiological mechanisms that pave the way for further drug discovery.
Investigators within the Molecular and Biochemical Pharmacology group strive to excel at biomedical research, professional education, and graduate education. The research projects within the group employ the whole range of modern biochemical, cell and molecular biological, physiological, and pharmacological methods to unravel the underlying cellular regulation and signaling mechanisms in disease states. These projects include studying:
inflammatory mechanisms in asthma
effects of hypoxia, aglycemia and inflammatory pain on endothelial cell permeability, resistance and cytoarchitecture at the blood brain barrier and using biotech approaches to targeting the blood-brain barrier for new drug development
mechanisms of sensory signaling from the skin
molecular mechanisms of pain
GABAergic signaling in chronic pain
activity-dependent control of protein synthesis
molecular cellular and organ based model systems to identify and validate novel drug targets for glaucoma
Follow the links below to learn more about the faculty and their research interests
A major focus of the Department of Pharmacology is Neuroscience research. Investigators in the department study the basic pharmacology of neurotransmission, how investigational drugs modulate this neurotransmission and how diseases that affect the brain might be better treated pharmacologically. Neuroscience research in the Department of Pharmacology includes drugs of abuse and substance abuse disorders, epilepsy and anticonvulsants, mechanisms of learning and memory, the impact of the blood brain barrier on disease and neuroactive drug penetration and mechanisms of chronic pain and analgesics. We study neural systems ranging from the peripheral sensory organs in the skin and eye to higher order brain centers involved in cognition.
In the area of Neuroscience, the Department of Pharmacology contains a large number of investigators studying basic mechanisms of pain and how clinical pain conditions can be better managed pharmacologically. Pain is ordinarily experienced as a transient event produced by events that result in, or has the potential to cause injury. From an evolutionary standpoint, normal pain sensitivity is protective, leading to avoidance of dangerous situations. Chronic pain, on the other hand, is a maladaptive and debilitating condition that can last for many months or even years. Such pain exerts a high social cost in terms of productivity, economic impact, and most importantly, quality of life.
Chronic pain can result from nerve trauma as in instances of neuropathic pain, persistent inflammation as in conditions of rheumatoid arthritis, or disease as with diabetes or cancer. Currently available therapies have limited success in treating chronic pain and are associated with disabling, often intolerable, side effects. Thus there is an urgent need to develop new mechanism-based therapies.
Investigators within the Arizona Pain Research Group examine factors driving chronic pain across a wide range of clinically relevant pain models. Current areas of investigation include cancer pain, skeletal pain, neuropathic pain, headache pain, and inflammation-induced pain. The expertise of the individual investigators encompass a spectrum of molecular, neurobiological and neuropharmacological techniques allowing for powerful collaborative efforts designed to address the question of the underlying causes of chronic pain. Such efforts will lead to discoveries of new targets for drug development with the ultimate goal of improved pain management.
In addition, ongoing collaborations with other groups within and outside the University of Arizona are actively exploring the development of novel pharmacological compounds. The goal in designing these novel agents is to provide better pain relief for chronic pain patients while minimizing adverse side effects associated with many current pain management therapies.