Daryl L. Davies, PhD
Faculty Directory

Daryl L. DaviesPhD

Daryl L. DaviesPhD

Associate Dean for Undergraduate Education & Professor of Clinical Pharmacy

Titus Family Department of Clinical Pharmacy

Daryl Davies is associate dean for undergraduate education and a professor in the Titus Family Department of Clinical Pharmacy at the USC School of Pharmacy. As associate dean, he is responsible for the ongoing development and management of the school’s undergraduate majors and minors. Davies is also the director of the master’s program in management of drug development in the Department of Regulatory and Quality Sciences and undergraduate faculty adviser for the Trojan Admission Pre-Pharmacy (TAP) program. He is a mentor in the STAR program—a cooperative venture in science education between the USC Health Sciences Campus and Francisco Bravo Medical Magnet High School in East Los Angeles—after several years serving as the program’s director.

In addition to his educational activities, Davies leads a research team at USC that is working to discover and develop novel therapeutics for the treatment of neurodegenerative diseases and alcoholism. He is considered a pioneer by his peers in the field of purinergic receptors and their role in central nervous system regulation of alcohol-induced changes in alcohol intake and signaling. He also is one of the lead faculty members in the USC Institute for Addiction Science.

Davies is a firm believer in using an interdisciplinary approach. To this end, his group works with a team of collaborators that use a combination of pharmacological, toxicological, electrophysiological, molecular, computational chemistry, molecular modeling and regulatory expertise to discover and develop new drugs.

Areas of Expertise

  • Purinergic receptors
  • Opioid Abuse
  • Neuro-psychiatric Disorders
  • Drug Safety Pharmacology and Toxicology
  • Drugs of Abuse Pharmacology and Toxicology
  • Early Stage Drug Discovery and Development
  • Neuro-degenerative Disorders
  • Alcohol Abuse
  • Education

    USC School of Pharmacy

    PhD

    California State University

    MA

  • Links
  • Selected Articles

    Dopamine Receptor Blockade Attenuates Purinergic P2X4 Receptor-Mediated Prepulse Inhibition Deficits and Underlying Molecular Mechanisms

    Front Cell Neurosci.

    2019 Sensorimotor gating refers to the ability to filter incoming sensory information in a stimulus-laden environment and disruption of this physiological process has been documented in psychiatric disorders characterized by cognitive aberrations. The effectiveness of current pharmacotherapies for treatment of sensorimotor gating deficits in the patient population still remains controversial.

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    A newly developed anesthetic based on a unique chemical core

    Proceedings of the National Academy of Sciences
    Noëlie S. Cayla, Beza A. Dagne, Yun Wu, Yao Lu, Larry Rodriguez, Daryl L. Davies, Eric R. Gross, Boris D. Heifets, M. Frances Davies, M. Bruce MacIver, and Edward J. Bertaccini

    Intravenous anesthetic agents are associated with cardiovascular instability and poorly tolerated in patients with cardiovascular disease, trauma, or acute systemic illness. We hypothesized that a new class of intravenous (IV) anesthetic molecules that is highly selective for the slow type of γ-aminobutyric acid type A receptor (GABAAR) could have potent anesthetic efficacy with limited cardiovascular effects. Through in silico screening using our GABAAR model, we identified a class of lead compounds that are N-arylpyrrole derivatives. Electrophysiological analyses using both an in vitro expression system and intact rodent hippocampal brain slice recordings demonstrate a GABAAR-mediated mechanism. In vivo experiments also demonstrate overt anesthetic activity in both tadpoles and rats with a potency slightly greater than that of propofol. Unlike the clinically approved GABAergic anesthetic etomidate, the chemical structure of our N-arylpyrrole derivative is devoid of the chemical moieties producing adrenal suppression. Our class of compounds also shows minimal to no suppression of blood pressure, in marked contrast to the hemodynamic effects of propofol. These compounds are derived from chemical structures not previously associated with anesthesia and demonstrate that selective targeting of GABAAR-slow subtypes may eliminate the hemodynamic side effects associated with conventional IV anesthetics.

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    P2X7 Receptor Antagonist A804598 Inhibits Inflammation in Brain and Liver in C57BL/6J Mice Exposed to Chronic Ethanol and High Fat Diet

    Journal of Neuroimmune Pharmacology
    Daniel FreireRachel E. ReyesAred BaghramDaryl L. DaviesLiana Asatryan

    Chronic low-grade neuroinflammation is increasingly implicated in organ damage caused by alcohol abuse. Purinergic P2X7 receptors (P2X7Rs) play an important role in the generation of inflammatory responses during a number of CNS pathologies as evidenced from studies using pharmacological inhibition approach. P2X7Rs antagonism has not been tested during chronic alcohol abuse. In the present study, we tested the potential of P2X7R antagonist A804598 to reduce/abolish alcohol-induced neuroinflammation using chronic intragastric ethanol infusion and high-fat diet (Hybrid) in C57BL/6J mice. We have previously demonstrated an increase in neuroinflammatory response in 8 weeks of Hybrid paradigm. In the present study, we found neuroinflammatory response to 4 weeks of Hybrid exposure. A804598 treatment reversed the changes in microglia and astrocytes, reduced/abolished increases in mRNA levels of number of inflammatory markers, including IL-1β, iNOS, CXCR2, and components of inflammatory signaling pathways, such as TLR2, CASP1, NF-kB1 and CREB1, as well in the protein levels of pro-IL-1β and Nf-kB1. The P2X7R antagonist did not affect the increase in mRNA levels of fraktalkine (CX3CL1) and its receptor CX3CR1, an interaction that plays a neuroprotective role in neuron-glia communication. P2X7R antagonism also resulted in reduction of the inflammatory markers but did not alter steatosis in the liver. Taken together, these findings demonstrate how P2X7R antagonism suppresses inflammatory response in brain and liver but does not alter the neuroprotective response caused by Hybrid exposure. Overall, these findings support an important role of P2X7Rs in inflammation in brain and liver caused by combined chronic alcohol and high-fat diet.

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    Si-LENT [Brain] Slice Recordings: a Novel Method for the Ex Vivo Genetic Modification of Neurons

    The FASEB Journal
    Larry Rodriguez, Chang You, Mark Brodie, and Daryl Davies

    Understanding the function of a specific receptor in a cell is key for developing new therapies for diseases. Current early-stage drug development strategies often utilize non-specific or “dirty” drugs/molecules to determine receptor function, as more specific agonists or antagonists may not be available. A second strategy incorporates genetic modifications to determine the role of a receptor in an animal model of disease. This method is time-consuming, expensive, and can produce artifacts that confound or skew results. Furthermore, certain modifications may not produce viable offspring. These issues make developing drugs for neurological conditions more challenging, as the function of a receptor can depend on the brain region where a neuron is located or can require an interaction partner (receptor cross-talk). One way to study neurons is to perform extracellular recordings on mouse or rat brain slices. In these experiments, an electrode is placed near, but not onto or into, a neuron. This electrode, usually filled with a saline solution, measures the number of action potentials over time, a.k.a. the firing rate. Agonists and/or drugs are then perfused on to the neuron, and the effects are reported as a change in the firing rates. Here, we describe a new method: “SiRNA-Loaded Electrodes kNocksdown Target (Si-LENT)” slice electrophysiology. Si-LENT slice is a new method for performing extracellular recordings in brain slice that can knockdown target genes over the course of a recording session. Si-LENT slice incorporates SiRNA into the recording electrode, which is delivered to the cell during the experiment. For the current study, we targeted P2X4 receptors, which we have previously linked to regulation of alcohol consumption. We recorded from dopaminergic (DAergic) neurons located in the ventral tegmental area (VTA) of the mouse brain. DAergic neurons in the VTA of the brain have been shown to be associated with learning, reward, and addiction, but the function of P2X4 receptors in this region is not well understood. We found a significant reduction in receptor activity after two hours of recording, and a sustained reduction for up to two hours thereafter.

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    Murine Drinking Models in the Development of Pharmacotherapies for Alcoholism: Drinking in the Dark and Two-bottle Choice

    JoVE (Journal of Visualized Experiments)
    Nhat Huynh, Natalie M Arabian, Liana Asatryan, Daryl L Davies

    Alcohol Use Disorder (AUD) is a major problem with more than an estimated 76 million people worldwide meeting the diagnostic criteria. Current treatments are limited to three FDA-approved medications that are largely ineffective even when combined with psychosocial intervention, as is evident by the high relapse rate. As such, the search for more novel treatments represents an important public health goal. To this end, the following protocol utilizes two simple rodent drinking models to assess the preclinical efficacy of lead anti-alcohol compounds: two-bottle choice (TBC) and drinking in the dark (DID). The former allows mice to voluntary drink in moderation while the latter induces mice to voluntary consume a large amount of alcohol in a short period that mimics binge drinking. The simple and high throughput nature of both of these paradigms allow for rapid screening of pharmacological agents or for identifying strains of mice that exhibit certain voluntary drinking behavior.

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    Preclinical evaluation of avermectins as novel therapeutic agents for alcohol use disorders

    Psychopharmacology (Berl)

    2018 The deleterious effects of alcohol use disorders (AUDs) on human health have been documented worldwide. The enormous socioeconomic burden coupled with lack of efficacious pharmacotherapies underlies the need for improved treatment strategies. At present, there is a growing body of preclinical evidence that demonstrates the potential of avermectins [ivermectin (IVM), selamectin (SEL), abamectin (ABM), and moxidectin (MOX)] in treatment of AUDs.

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    Macrophage P2X4 receptors augment bacterial killing and protect against sepsis

    JCI Insight
    Balázs Csóka, Zoltán H Németh, Ildikó Szabó, Daryl L Davies, Zoltán V Varga, János Pálóczi, Simonetta Falzoni, Francesco Di Virgilio, Rieko Muramatsu, Toshihide Yamashita, Pál Pacher, György Haskó

    The macrophage is a major phagocytic cell type, and its impaired function is a primary cause of immune paralysis, organ injury, and death in sepsis. An incomplete understanding of the endogenous molecules that regulate macrophage bactericidal activity is a major barrier for developing effective therapies for sepsis. Using an in vitro killing assay, we report here that the endogenous purine ATP augments the killing of sepsis-causing bacteria by macrophages through P2X4 receptors (P2X4Rs). Using newly developed transgenic mice expressing a bioluminescent ATP probe on the cell surface, we found that extracellular ATP levels increase during sepsis, indicating that ATP may contribute to bacterial killing in vivo. Studies with P2X4R-deficient mice subjected to sepsis confirm the role of extracellular ATP acting on P2X4Rs in killing bacteria and protecting against organ injury and death. Results with adoptive transfer of macrophages, myeloid-specific P2X4R-deficient mice, and P2rx4 tdTomato reporter mice indicate that macrophages are essential for the antibacterial, antiinflammatory, and organ protective effects of P2X4Rs in sepsis. Pharmacological targeting of P2X4Rs with the allosteric activator ivermectin protects against bacterial dissemination and mortality in sepsis. We propose that P2X4Rs represent a promising target for drug development to control bacterial growth in sepsis and other infections.

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  • Affiliations
    • Research Society on Alcoholism

    • Society for Neuroscience

    • International Society for Biomedical Research on Alcoholism

    • Drug Information Association

    • American Society for Pharmacology and Experimental Therapeutics

  • Accomplishments

    Former Director, USC STAR/EHA Program

    USC's Science, Technology and Research (STAR) Program brings together USC scientists and engineers with Francisco Bravo Medical Magnet High School students in Los Angeles. STAR students learn about science and math by conducting research that matters with USC experts.

  • Patents

    Compositions and methods for parkinson's disease therapy

    US20180271888A1

    2018 This disclosure provides methods for the treatment of one or more of: Parkinson's disease (PD); PD symptoms; movement disorders; neurodegenerative diseases linked to changes in dopamine, dopamine signaling, or dopamine expression, in a subject in need thereof comprising administering to the subject an effective amount of an agent that potentiates dopaminergic neurotransmission. Also provided is a method for selecting a candidate agent for the treatment of Parkinson's disease (PD); PD symptoms; and neurodegenerative diseases linked to changes in dopamine, dopamine signaling, or dopamine expression.

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    Ivermectin Antagonizes Ethanol Inhibition in P2X4 Receptors

    8796230 B2

    2014 A method for reducing alcohol consumption in a subject includes a step of identifying a subject exhibiting at least one symptom of alcoholism and then administering a therapeutically effective amount of an Ivermectin analogue-containing composition to the subject. A method of screening Ivermectin analogues for reducing alcohol consumption is also provided.

  • Research Grants

    Regulation of Alcohol Intake by Purinergic P2X4 Receptors

    NIH/NIAAA,

    09/05/16-06/30/21 Role: PI We have identified P2X4Rs as targets for the development of drugs to prevent and/or treat alcohol use disorders (AUDs). Findings, to date, support developing novel therapeutic agents for AUDs that focus on this largely unexplored target. The proposed studies test the hypothesis that P2X4Rs within the brain dopamine reward system regulate ethanol intake. Results from these investigations should provide significant new mechanistic insight into how P2X4Rs affect alcohol intake by 1) Interrogating the role of P2X4Rs in reward systems linked alcohol intake and 2) Providing new insights regarding the molecule cascade that P2X4Rs participate in resulting in the modulation of alcohol intake.

    GABA-A α5

    AgeneBio,

    08/15/2019– 07/31/2020 Role: PI of Subcontract Phase I Structurally Diverse GABA-A α5 Positive Allosteric Modulators for Treatment of MCI due to AD. In this project, Dr. Davies is participating in a research project with AgeneBio (Rosenzweig-Lipson, Sharon, PI) under a SBIR subcontract. This research project focuses on testing of lead series and lead series optimized compounds to determine their selectivity as α5 GABAA receptor modulators.

  • Multimedia
    • Daryl L. Davies, PhD
    • Daryl L. Davies, PhD
  • Selected Media Appearances

    Daryl Davies Appointed Associate Dean for Undergraduate Education

    USC School of Pharmacy | 05/09/2019

    Daryl Davies, PhD has been appointed to the newly-created role of associate dean for undergraduate education at the USC School of Pharmacy.

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    Traditional Chinese hangover cure seen as potential Alzheimer’s disease treatment

    USC News | 08/20/2018

    “For example, she has great anecdotal evidence for DHM’s potential effectiveness against Parkinson’s disease,” said Daryl Davies, a professor in the USC School of Pharmacy’s Titus Family Department of Clinical Pharmacy who is collaborating with Liang on this research. He added that DHM also might prove useful in treating anxiety, alcohol-use disorder and PTSD. Another advantage is that, unlike current anxiety and alcohol-withdrawal medications such as diazepam, DHM is non-addictive...

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    High schooler researches alongside USC pharmacologists, locks down Harvard early

    USC News | 01/29/2018

    Kiamehr is a 17-year-old high school senior, but it would be easy to mistake him for a graduate student: He’s in the pharmaceutical lab of Professor Daryl Davies at the USC Health Sciences Campus nearly every day.

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    Yes, it’s true: Wine is good for you — to a point

    USC News | 01/17/2018

    “Antioxidants in wine are so low that it’s a joke,” according to Professor Daryl Davies, a USC neuro-pharmacologist who researches alcohol and drugs of abuse...

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    USC School of Pharmacy offers undergraduate pharmacology degree

    USC News | 10/04/2017

    “The focus of the program is translating basic discoveries into the clinic, and how our clinical knowledge benefits human health,” said Daryl Davies, the school’s director of undergraduate programs. He notes that the program’s blend of science with clinical applications will give students a competitive advantage over their peers in applying for medical, dental or pharmacy schools or PhD programs...

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