1) Animal models of alcohol and drug abuse -
My work involves using and developing animal models that can be used to identify medications for substance abuse. In addition to medication development, the models are also used in studies aimed at examining the etiology of drug abuse, and its underlying mechanisms.The models involve behavioral effects that range from directly observable effects (e.g., drug-induced motor impairment) to effects examined by conditioning procedures (e.g., conditioned place preference, which is related to rewarding effects of drugs, and discriminative stimulus effects, which are related to subjective drug effects in humans). |
2) Etiology of drug and alcohol abuse -
Many people drink and/or use drugs recreationally, particularly during adolescence, but only some become addicted. Genetic factors likely play a role, but environmental factors may also be involved. To study interactions between genetic make-up and environmental conditions, models in mice are especially useful. Initiation of drug abuse occurs primarily during adolescence, and during this developmental period alcohol and drugs of abuse may have distinct effects that could increase risk for abuse. In mice, adolescence has been defined as spanning from postnatal days 28-42. Thus, procedures useful to study drug effects during adolescence in mice have to be rapid enough to be conducted within a two-week period. One of the current priorities in my lab is the development of rapid behavioral procedures suitable to examine developmental aspects of abuse related drug effects in mice, the species of choice for the experimental study of gene-environment interaction. These procedures will be used to learn more about
risk factors for the abuse of alcohol and for the rising abuse of prescription opioid analgesics by adolescents. This research, which is supported in part by an NIH grant (NIAAA), and by the START Center Medication Development Endowment, will increase our understanding of risk factors for alcoholism and drug abuse, and will help the development of effective approaches to prevention and treatment. |
3) Mechanistic studies -
The pharmacological mechanisms by which drugs produce their abuse-related effects are, for the most part, poorly understood. Abuse potential of a particular drug is likely related to its subjective effects, and subjective effects of drugs in humans can often be predicted from drug discrimination experiments in animals. The discriminative stimulus effects of most drugs involve several different receptor mechanisms; some of which may be unique to that drug and some which are common with other drugs. Current efforts, supported by an NIH grant (NIDA), are aimed at understanding the mechanism of action of gamma-hydroxybutyrate (GHB). GHB is abused primarily by adolescents and young adults, and is often taken together with alcohol and with other ?club drugs? such as ketamine. Abuse of such drugs continues to play a major role in the spread of HIV, by altering judgment that leads to impulsive high-risk sex. By identifying the role of specific receptors in abuse, future studies may be better able to develop
specific, pharmacologically targeted therapies for drugs of abuse. |
4) Drug discovery and development -
I have worked for 15 years in the pharmaceutical industry, where I have directed drug discovery projects aimed at identifying novel treatments for central nervous system disorders. My experience in industry benefits UTHSCSA in at least two ways. First, it helps me teaching Psychiatry residents to critically evaluate studies that claim effectiveness and superiority of novel drugs acting on the central nervous system. Second, having experience both in the pharmaceutical industry and in academia enables me to provide graduate students with a balanced but experienced first-hand perspective of both settings. Graduate students are generally more naive about research in industry than in academia. Learning about research in industry widens career opportunities for students, and may help to meet the pressing and currently unmet need for scientists in the biopharmaceutical industry. Teaching about industrial research by offering a formal program in Drug Discovery and Development would fill an important void and
would give UTHSCSA a competitive edge, because at present only one university in the USA that is taking steps to initiate such a training program. |
| Date |
Description |
Institution |
# Students |
| 1/2014 - Present |
Membership on Supervising Committee |
UTHSCSA |
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| 1/2014 - Present |
Membership on Supervising Committee |
UTHSCSA |
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|
| 8/2011 - Present |
Chalk Talks - NIDA T32 postdoctoral training grant |
UTHSCSA |
15 students |
| 1) Drug discovery and development: views from industry and academia
2) Detecting dubious data & what`s a p-value anyway?
3) If it doesn`t fit, you must refit: analysis of dose-response data |
| 3/2010 - Present |
Membership on Supervising Committee |
|
|
|
| 3/2010 - Present |
Membership on Supervising Committee |
|
|
|
| 1/2010 - Present |
Drug Discovery and Development Committee (Chair) |
|
|
| The mission of this subcommittee of the Education Committee of the Department of Pharmacology is to explore various options for a drug discovery and development program. |
| 1/2008 - Present |
Special Topics: Microelectives |
The University of Texas Health Science Center |
|
| Course Director - This course, entitled "Drug Discovery: Nuts and Bolts", is aimed at familiarizing graduate students with the history of drug discovery, its current status, and future directions. Students are generally more naive about research in industry than in academia. The aim of this course is to provide an opportunity to learn about research in industry. This course could provide a basis for a more extensive training program in Drug Discovery and Development. There are many reasons to initiate such a program, such as the pressing and currently unmet need for scientists in the biopharmaceutical industry, and the considerable interest of students to learn about a career in industry versus a career in academia. |
| 6/2007 - Present |
Journal Club Psychiatry Residents |
|
|
| The journal club teaches residents to critically evaluate clinical studies. I specifically help residents to examine studies that claim effectiveness and superiority of novel drugs acting on the central nervous system. Having worked for 15 years as CNS drug discovery researcher in the pharmaceutical industry helps me to teach a critical approach to such studies. |
| 4/2007 - Present |
Drug Development Initiative Group |
UTHSCSA |
|
| Requested by Dr. Alan Frazer, Chair of Pharmacology, and Dr. Bruce Nicholson, Chair of Biochemistry, I give a seminar on current approaches to drug discovery and development, based on my experience in the pharmaceutical industry. This seminar is aimed at helping to explore opportunities for medicinal chemistry at UTHSCSA. |
| 11/2006 - Present |
Seminar on Careers in Biomedical Sciences |
Our Lady of the Lake University |
10 students |
| This seminar is aimed at helping undergraduates decide their career. The seminar compares and contrasts biomedical research in industry and in academia, based on my experience in both work environments. Both provide many opportunities for scientific collaborations. |
| 9/2006 - Present |
Research Methods in Psychiatry |
|
|
| This course is aimed at teaching residents research methods in Psychiatry. I help them evaluate the usefulness of diagnostic tests, using concepts such as sensitivity and specificity. In addition to providing an overview of commonly used statistical tests, I focus on randomization tests, which are easy to understand, simple to compute, and especially useful in single case and small-n studies. Knowing how to apply these tests helps clinicians to evaluate, in a variety of settings including private practice, the effectiveness of interventions. |
| 8/2006 - Present |
Substance Abuse Seminars for PG1 residents |
|
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| This course teaches residents about substance use disorders and substance-induced disorders. I focus on stimulants, hallucinogens, phencyclidine and related drugs (e.g., ketamine), prescription drugs and over-the-counter medicines, inhalants, and, with the help of Dr. Brett Ginsburg, on cannabis. The emphasis is on the acute and chronic effects of these drugs, and on possible treatments. |
| 6/2004 - Present |
Research Methods in Psychiatry |
|
|
| Based on my experience in the pharmaceutical industry, I teach residents current approaches to discover and develop novel drugs for the treatment of central nervous system disorders. Knowledge about the drug discovery and development process helps residents to critically evaluate results of clinical studies with novel drugs. |
| 8/2003 - Present |
Psychiatry Grand Rounds |
|
|
| Based on my experience in the pharmaceutical industry, I teach residents current approaches to discover and develop novel drugs for the treatment of central nervous system disorders. Knowledge about the drug discovery and development process helps residents to critically evaluate results of clinical studies with novel drugs. |
| 1/2003 - Present |
Pharmacology Seminar |
The University of Texas Health Science Center |
|
| I give seminars for the Pharmacology Department that describe current approaches to drug discovery and development. Although graduate students have ample opportunity to familiarize themselves with research in academia, the same is not true for research in industry. The seminars are aimed at providing graduate students with a general introduction to research in the pharmaceutical industry. To provide more detail about drug discovery, I offer an additional course that is part of the Pharmacology Graduate Program. |
| 6/2002 - Present |
Biological Bases of Brain Function |
|
|
| As part of the summer undergraduate research program of the Department of Pharmacology, I give seminars that teach undergraduates about substance use disorders, their underlying mechanisms, and the animal models used to study these mechanisms. The overall aim is to help undergraduates decide to pursue an advanced degree and a career in the biomedical sciences. |
Abstract |
| Daws L, Mitchell N, Horton R, Vitela M, Gould G, Koek W. Transient increases in expression and function of the plasma membrane monoamine transporter may contribute to treatment resistant depression during juvenile and adolescent periods; 2014 Dec. (ACNP meeting).
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| Mitchell NC, Horton RE, Vitela M, Gould GG, Koek W, Daws LC. Antidepressant potential of organic cation transporter blockade: the role of norepinephrine; 2014 Apr. (ASPET meeting).
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| Koek W. Morphine-induced Conditioned Place Preference and effects of Morphine Pre-exposure in Adolescent and Adult Mice; 2013 Dec. (ACNP meeting).
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Journal Article |
| Krause-Heuer AM, Fraser-Spears R, Dobrowolski JC, Ashford ME, Wyatt NA, Roberts MP, Gould GG, Cheah WC, Ng CKL, Bhadbhade M, Zhang B, Greguric I, Wheate NJ, Kumar N, Koek W, Callaghan PD, Daws LC, Fraser BH. Evaluation of the antidepressant therapeutic potential of isocyanine and pseudoisocyanine analogues of the organic cation decynium-22 Eur J Med Chem 2017 Sep;137:476-487.
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| Mitchell NC, Bowman MA, Gould GG, Koek W, Daws LC. Ontogeny of Norepinephrine Transporter Expression and Antidepressant-Like Response to Desipramine in Wild-Type serotonin Transporter Mutant Mice Journal of Pharmacology and Experimental Therapeutics 2017 Jan;360(1):84-94.
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| Mecklenburg J, Patil M, Koek W, Akopian AN. Effects of local and spinal administrations of mu-opioids on postoperative pain in aged versus adult mice Pain Rep 2017 Jan;2(1).
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| Moerke MJ, De Moura FB, Koek W, McMahon LR. Effects of nicotine in combination with drugs described as positive allosteric nicotinic acetylcholine receptor modulators in vitro: discriminative stimulus and hypothermic effects in mice Eur J Pharmacol 2016 Sep;786:169-178.
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| Mitchell NC, Gould GG, Koek W, Daws LC. Ontogeny of SERT Expression and Antidepressant-like Response to Escitalopram in Wild-Type and SERT Mutant Mice J Pharmacol Exp Ther 2016 Aug;358(2):271-281.
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| Koek W. Morphine-induced conditioned place preference and effects of morphine pre-exposure in adolescent and adult male C57BL/6J mice Psychopharmacology (in press) 2016 Jul;233(11):2015-2024.
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| Serafine KM, Bentley TA, Kilborn DJ, Koek W, France CP. Drinking sucrose or saccharin enhances sensitivity of rats to quinpirole-induced yawning European Journal of Pharmacology 2015 Oct;764:529-536.
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| Gerak LR, Zanettini C, Koek W, France CP. Cross-tolerance to cannabinoids in morphine-tolerant rhesus monkeys Psychopharmacology (Berl) 2015 Oct;232(19):3637-3647.
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| Iderberg H, McCreary AC, Varney MA, Kleven MS, Koek W, Bardin L, Depoortere R, Cenci MA, Newman-Tancredi A. NLX-112, a novel 5-HT1A receptor agonist for the treatment of L-DOPA-induced dyskinesia: Behavioral and neurochemical profile in rat Exp Neurol 2015 Sep;271:335-350.
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| Collins GT, Chen Y, Tschumi C, Rush EL, Mensah A, Koek W, France CP. Effects of consuming a diet high in fat and/or sugar on the locomotor effects of acute and repeated cocaine in male and female C57Bl/6J mice Experimental and Clinical Psychopharmacology 2015 Aug;23:228-237.
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| Koek W, Gerak LR, France CP. Effects of amphetamine, morphine, and CP55, 940 on Go/No-Go task performance in rhesus monkeys Behav Pharmacol 2015 Aug;26(5):481-484.
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| Paredes RM, Piccart E, Navaira E, Cruz D, Javors MA, Koek W, Beckstead MJ, Walss-Bass C. Physiological and behavioral effects of amphetamine in BACE1 (-/-) mice Genes Brain Behav 2015 Jun;14(5):411-418.
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| Serafine KM, Bentley TA, Koek W, France CP. Eating high fat chow, but not drinking sucrose or saccharin, enhances the development of sensitization to the locomotor effects of cocaine in adolescent female rats Behav Pharmacol 2015 Apr;26(3):321-325.
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| Mitchell, N.C., Koek, W. and Daws, L.C. Antidepressant-like effects and basal immobility depend on age and serotonin transporter genotype Genes, Brain and Behavior 2015 Mar;4(17):543-549.
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| Koek W. Effects of repeated exposure to morphine in adolescent and adult male C57BL/6J mice: age-dependent differences in locomotor stimulation, sensitization, and body weight loss Psychopharmacology (Berl) 2014 Apr;231(8):1517-1529.
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| Collins GT, Jackson JA, Koek W, FRance CP. Effects of dopamine D(2)-like receptor agonists in mice trained to discriminate cocaine from saline: influence of feeding condition Eur J Pharmacol 2014 Apr;729:123-131.
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| Mitchell NC, Gould GG, Smolik CM, Koek W, Daws LC. Antidepressant-like drug effects in juvenile and adolescent mice in the tail suspension test: Relationship with hippocampal serotonin and norepinephrine transporter expression and function Front Pharmacol 2013 Oct;4:131-131.
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