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Daryl L. Davies

PIBBS MENTOR

Professor of Clinical Pharmacy


School of Pharmacy

Daryl L. Davies

Research Topics

  • Drugs of Abuse Pharmacology and Toxicology
  • Early Stage Drug Discovery and Development
  • Drug Safety Pharmacology and Toxicology
  • Neuro-degenerative Disorders
  • Neuro-psychiatric Disorders

Research Overview

Dr. Davies is a Professor in the Titus Family Department of Clinical Pharmacy at the University of Southern California. In addition, he is the Director of the MS program in Management of Drug Development which is part of the International Center of Regulatory Science at USC School of Pharmacy. Most recently, Dr. Davies has taken the lead role in the development and management of the School of Pharmacy's first undergraduate minor to be taught on the University Park Campus -- Minor in Science and Management of Biomedical Therapeutics. As part of this effort, he is one of the undergraduate faculty advisers for the School of Pharmacy Trojan Admission Pre-Pharmacy (TAP) Program.

Dr. Davies has over twenty-five years of research experience focused on the roles of ligand-gated ion channels and how ethanol (alcohol) affects these channels leading to changes in behavioral responses. He is recognized by his peers as a Pioneer in the field of alcohol research with a focus on purinergic, P2X4 receptors and their role in CNS regulation of alcohol-induced changes in signalling.

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

Current collaborative projects: 1) Investigations with Drs. Stan Louie, Liana Asatryan, Jing Liang, Kathy Rodgers and Eunjoo Pacifici (Pharmacy), Michael Jakowec and Daniel Holschneider (KECK) and Marco Bortolato (University of Utah). Dr. Davies, with this team of investigators is undertaking efforts to support a drug discovery program using ivermectin (IVM) as the lead compound for the development of novel P2X4 positive allosteric modulators. The long term translational aspects of this project focus on the development of therapeutic treatment strategies for the treatment of AUD. Dr. Davies' research is primarily funded by National Institute of Alcohol Abuse and Alcoholism (NIAAA). As a major step in this process, Dr. Davies' group has recently reported that Moxidectin (MOX), an IVM analogue, has lower neurotoxicity potential and improved margin of safety compared to IVM. In that MOX is currently becoming approved for human use for other indications (anti-parasitic), Dr. Davies' group is looking to repurpose MOX as a novel pharmacotherapy for AUD.

2) In collaboration with Dr. Jakowec, the Davies group is using a P2X4KO mouse model as a tool for the investigation of changes in signaling pathways that have been linked to neuro-developmental disorders such as autism spectrum disorder, fragile X syndrome and schizophrenia. This line of investigation stems from recent findings suggesting that knocking out the p2rx4 gene (P2XKO model) leads to significant changes in glutamate receptor (i.e., NMDARs and AMPARs) expression across several different brain regions. Building evidence indicates that changes in glutamate expression and function have been associated with gene transcription and protein translation linked to neurodevelopmental issues.

3) In collaboration with Dr. Jakowec, a new avenue of research that proposes to investigate the potential role of experience-dependent neuroplasticity as a therapeutic target in treating AUD as well as other neuro-degenerative diseases including Parkinson?s disease is developing. Studies in this effort have brought together the expertise of the two groups together resulting in a novel and innovative set of studies.

4) Investigations with Drs. Asatryan and Liang (faculty in the Davies laboratory) are focusing on investigating the action of alcohol on GABAA and, Glycine receptors. The long term goal of this work focuses on the development of pharmacotherapeutic treatment strategies for the treatment of alcohol abuse and alcoholism. This collaborative effort is also being supported by collaborations with Drs. James Trudell (Stanford University) and Gregg Homanics (University of Pittsburg). Together this effort is resulting in new molecular models of alcohol action and a new line of transgenic animals that will provide novel methods of investigation into brain region specificity of alcohol action. Interestingly, during the course of these efforts, we identified a novel brain mapping technique that will be useful to the neuroscience and alcohol research communities.

5) Investigations with Drs. Liang and Holschneider are resulting in the development of a series of neutraceuticals for the treatment of anxiety disorders. Notably, anxiety disorders are the most common mental illness in the U.S., affecting 40 million adults in the United States age 18 and older (18% of U.S. population) and have been estimated to consume almost one-third of the country?s mental health bill in excess of $42 billion a year. Currently, there are a number of clinically effective treatments for anxiety and associated psychiatric conditions, but unfortunately, a large segment of patient?s exhibit treatment-resistance to first-line interventions or substantial side effects due to the drugs illustrating the critical need for new pharmacotherapies for the treatment of anxiety.

6) In collaboration with Dr. Frances Richmond (USC International Center of Regulatory Science), Dr. Davies directs the Masters program in Management of Drug Development. The MS program in the Management of Drug Development at USC is a novel degree program designed for students with a background in preclinical biological and/or pharmaceutical sciences. It aims at producing entry- and mid-level practitioners with the knowledge and skills appropriate for professional practice in translational research, with particular emphasis on the area of transition between early stage preclinical drug discovery and clinical drug development. This area, commonly referred to as the "valley of death," represents one of the most challenging and important areas in translational research, yet programs designed to train and educate future translational science leaders are lacking. In collaboration with Dr. Richmond he also Directs the new undergraduate minor in Science and Management of Biomedical Therapeutics. This new program provides preparatory training to undergraduate students in fields related to Pharmacy and Medicine . Courses in this minor will also introduce undergraduate students to drug and device development by presenting topics and case studies related to the regulatory challenges associated with the discovery and development of biomedical products. Overall, the courses will provide foundational knowledge that will lead to new opportunities in careers in the biomedical industry, life sciences, nutrition and food sciences, diagnostics, drug and medical devices.

http://www.ncbi.nlm.nih.gov/myncbi/browse/collection/41161689/?sort=date&direction=ascending

Contact Information

Mailing Address 9121
Office Location PSC 506
Office Phone (323) 442-1427
Lab Location PSC 400 and 500
Lab Phone (323) 442-1426
Fax (323) 442-1704
Office Location PSC 506

Websites

Education

  • MA 1992 Biology (Emphasis Molecular Biology) - California State University, Dominguez Hills
  • Ph.D. 1996 Molecular Pharmacol & Toxicology - University of Southern California, School of Pharmacy

Selected Publications

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  • Khoja S, Shah V, Garcia D, Asatryan L, Jakowec MW, Davies DL. Role of purinergic P2X4 receptors in regulating striatal dopamine homeostasis and dependent behaviors. J Neurochem. 2016 Jul 12. doi: 10.1111/jnc.13734. PubMed Link
  • Asatryan L, Khoja S, Rodgers KE, Alkana RL, Tsukamoto H, Davies DL. Chronic ethanol exposure combined with high fat diet up-regulates P2X7 receptors that parallels neuroinflammation and neuronal loss in C57BL/6J mice. J Neuroimmunol. 2015 Aug 15;285:169-79. PubMed Link
  • Huynh N, Arabian N, Lieu D, Asatryan L, Davies DL Utilizing an Orally Dissolving Strip for Pharmacological and Toxicological Studies: A Simple and Humane Alternative to Oral Gavage for Animals. J Vis Exp. 2016 Mar 23;(109):e53770. PubMed Link
  • Franklin K.M., Asatryan L., Jakowec M.W., Trudell J.R., Bell R.L. and Davies D.L. P2X4 receptors (P2X4Rs) represent a novel target for the development of drugs to prevent and/or treat alcohol use disorders. Front Neurosci. 2014 Review. PubMed
  • Davies DL, Bortolato M, Finn DA, Ramaker MJ, Barak S, Ron D, Liang J and Olsen RW. Recent advances in the discovery and preclinical testing of novel compounds for the prevention and/or treatment of alcohol use disorders, Alcohol Clin Exp Res, 37: 8-15, 2013

    PubMed
  • Wyatt L.R., Godar S.C., Khoja S., Jakowec M.W., Alkana R.L., Bortolato M. and Davies D.L. Socio-communicative and sensorimotor impairments in male P2X4-deficient mice. Neuropsychopharmacology. 2013 38:1993-2002.

    PubMed
  • Yardley M, Wyatt L, Khoja S, Asatryan L, Ramaker MJ, Finn DA, Alkana RL, Huynh N, Louie SG, Petasis, NA, Bortolato M and Davies DL. Ivermectin Reduces Alcohol intake and preference in Mice. Neuropharmacology, 63:190-201, 2012 PubMed
  • Bortolato M, Yardley M, Khoja S, Godar SC, Asatryan L, Finn DA, Huynh N, Alkana RL, Louie SG and Davies DL. Pharmacological insights into the role of P2X4 receptors in behavioral regulation: lessons from ivermectin, Int J Neuropsychopharmacology, 2013 16:1059-1070.

    PubMed
  • Asatryan L,Popova M,Perkins D,Trudell JR,Alkana RL,Davies DL -Ivermectin antagonizes ethanol inhibition in purinergic P2X4 receptors.- J Pharmacol Exp Ther [2010] Sep 1;334(3):720-8 PubMed
  • Popova M,Asatryan L,Ostrovskaya O,Wyatt LR,Li K,Alkana RL,Davies DL - A point mutation in the ectodomain-transmembrane 2 interface eliminates the inhibitory effects of ethanol in P2X4 receptors. - J Neurochem [2010] Jan;112(1):307-17 PubMed