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Myers Laboratory

UTHealth School of Dentistry Research Labs

Overview

The long-term goal of Dr. Myers’ research is to generate novel scientific information that ultimately improves and advances human health.  A major focus is studying the pernicious areca nut, one of the most widely abused substances in the world and a potent oral carcinogen. Although areca nut consumption is well-documented outside of the US, its use/abuse among immigrant populations in the US is poorly understood.  His recent published work demonstrated that a multitude of commercialized areca nut products can be easily purchased in Houston retail markets.  In the laboratory, he studies how humans metabolize toxic constituents of the nut, collectively called the areca alkaloids, and how these nitrogenous chemicals interact with alcohol and menthol in the liver.
Another facet of Dr. Myers’ research is in improving pharmaceutical waste management. Specifically, he collaborates with an industry partner to develop safe and effective ways to destroy leftover propofol intravenous solutions which are normally prone to contamination by microbial pathogens if not properly disposed.
Another facet of Dr. Myers’ research includes pharmacokinetic trials – to enhance knowledge about the absorption, metabolism, disposition and excretion (ADME) of medications.  In collaboration with colleagues at M.D. Anderson Cancer Center, he aims to discover if blood levels of varenicline (Chantix), a drug approved by the FDA to assist in smoking cessation, and/or genetic make-up can predict treatment outcomes (cessation).  He also collaborates M.D. Anderson Cancer Center investigators to determine the influence of genetic variations of UGT isoenzymes on the pharmacokinetics and analgesic activity of hydromorphone (Dilaudid) in cancer patients. In the stem cell transplant setting, Dr. Myers maintains a keen interest in studying busulfan, specifically how it interacts with other drugs and the role of its unique metabolite, EdAG, in mediating treatment-related cellular toxicity.

Projects

  • Role of Glutathionylation in Busulfan Biotoxification

    Role of Glutathionylation in Busulfan Biotoxification

    Overview/Research: Busulfan is an alkylating agent used in chemotherapy conditioning regimens prior to hematopoietic stem cell transplantation (HSCT). However, its administration is associated with a daunting risk of adverse toxicities, which have been historically attributed to busulfan's mechanism of non-specific DNA alkylation. A phase II generated metabolite of busulfan, EdAG (γ-glutamyldehydroalanylglycine), is a dehydroalanine analog of glutathione with an electrophilic moiety, suggesting it may bind to proteins and disrupt biological function. In this project, we have initially shown the EdAG spontaneously reacts with endogenous thiols (glutathione and cysteine) and inhibits hTrx-1, likely biochemically relevant events in humans prescribed busulfan. These findings continue to support the growing concept that EdAG, an underrecognized phase II metabolite of busulfan, plays a role in untoward cellular toxicities during busulfan pharmacotherapy.

    Team Members

    Stephanie Hoang (Loyola University New Orleans)

    Nhu Dao, BS (DS2)

    Publications

    Peer-reviewed Article:

    Hoang S, Dao N, Myers AL. Electrophilic reactivity of the Busulfan metabolite, EdAG, towards cellular thiols and inhibition of human thioredoxin-1. Biochem Biophys Res Commun. 2020 Dec 10;533(3):325-331.

  • Novel Toxicokinetic Drug Interactions with Areca Alkaloids

    Novel Toxicokinetic Drug Interactions with Areca Alkaloids

    Although the consumption of areca products has been known since antiquity, very little is known about how alkaloids present in the nut interact with other drugs of abuse, OTC agents, or FDA-approved medications. Our preliminary research demonstrates that arecoline is rapidly metabolized to arecaidine by human liver. In addition, we found that arecoline possibly interacts with ethanol, forming a novel transesterification product with unknown pharmacology.

    Team Members

    Vincenzo Paolillo, PhD (UT M.D. Anderson Cancer Center)

    Nhu Dao, BS (DS2)

    Henry Touchton, BS (DS2)

    Publications

    Abstract:

    N. Dao , V. Paolillo , S. Hoang , A. L. Myers. Degradation and Ethanolic Transesterification of Arecoline, a Betel Nut Toxin. AADR/IADR Annual Meeting, 2020.

  • Celecoxib for acute post-operative pain following impacted third molar surgery

    Celecoxib for acute post-operative pain following impacted third molar surgery

    Overview/Research: The type of drugs called non-steroidal anti-inflammatory drugs (NSAIDs) are used widely in dental pain management. Even so, the potential for gastrointestinal upset and bleeding still occurs since these drugs are not specific for pain pathways. Selective pain blockers, such as celecoxib, have an advantage as they have less side effects on the gastrointestinal tract but their role in treating pain of dental origin is still largely unknown. Dr. Myers is a co-investigator (co-I) on a clinical trial – the goal is to determine if administration of celecoxib (Celebrex) plus acetaminophen (Tylenol) prior to third molar (“wisdom teeth”) extraction reduces pain.

    Team Members

    Harry D. Gilbert, DDS (PI)

    Arthur H. Jeske, DDS, PhD (co-I)

    Cassandra Barnes, BS (DS4)

    Jane Lee, BS (DS2)

    Caroline Cutbirth, BS (DS2)

  • Implications of Areca Nut Use/Abuse in the US

    Implications of Areca Nut Use/Abuse in the US

    Consumption of the areca (betel) nut is the world's fourth-most common addictive habit, only after caffeine, alcohol, and nicotine. Mastication of the nut releases psychoactive alkaloids that produce greater alertness, a tingling sensation in the body, and euphoria. Consumption is prevalent in many Asia-Pacific countries, but also within immigrant populations in Europe and North America. Regarding use/abuse in the US, data are limited to mostly case/anecdotal reports, and some published literature. In this project we are attempting to learn more about the retail access of areca products in Houston, TX and elucidate the public health ramifications.

    Team Members

    Sayali Tungare, BDH, MPH

    Khairunisa Hashmani, RDH, MA

    Vanna Hovanky, MS (DS2)

    Publications

    Peer-reviewed Article:

    Tungare S, Myers AL. Retail Availability and Characteristics of Addictive Areca Nut Products in a US Metropolis. J Psychoactive Drugs. 2021 Jan 25;1-16

  • Pharmacokinetic & Pharmacogenetic Trials

    Pharmacokinetic & Pharmacogenetic Trials

    Overview/Research: Dr. Myers collaborates on pivotal pharmacokinetic and pharmacogenetic trials with colleagues at MD Anderson Cancer Center. The overall aim of these trials is to determine if genetic variations in drug metabolizing enzymes and drug transporters influences the pharmacokinetics of medications and consequent treatment outcomes. Drugs of interest include hydromorphone (Dilaudid) and varenicline (Chantix).

    Team Members

    Paul Cinciripini, PhD (MD Anderson Cancer Center; PI)

    Joseph A. Arthur, MD (MD Anderson Cancer Center; PI)

    Peiying Yang, PhD (MD Anderson Cancer Center)

Lab Team

Alan L. Myers, PharmD, PhD, RPh
Associate Professor
[email protected]
713-486-4508
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Key Publications

Macdonell M, Kawedia JD, Zhang YP, Roux R, Myers AL. Chemical Degradation of Intravenous Chemotherapy Agents and Opioids by a Novel Instrument. Hosp Pharm. 2021 Oct;56(5):576-583.

Tungare S and Myers AL. Retail Availability and Characteristics of Addictive Areca Nut Products in a US Metropolis. J Psychoactive Drugs. 2021 Jul-Aug;53(3):256-271.

Hoang S, Dao N, Myers AL. Electrophilic reactivity of the Busulfan metabolite, EdAG, towards cellular thiols and inhibition of human thioredoxin-1. Biochem Biophys Res Commun. 2020 Dec 10;533(3):325-331.                                                                                                                           

Desta Z, Gammal RS, Gong L, Whirl-Carrillo M, Gaur AH, Sukasem C, Hockings J, Myers A, Swart M, Tyndale R, Masimirembwa C, Iwuchukwu OF, Chirwa S, Lennox J, Gaedigk A, Klein T, Haas DW. Clinical Pharmacogenetics Implementation Consortium (CPIC) Guideline for CYP2B6 and Efavirenz-containing Antiretroviral Therapy. Clin Pharmacol Ther. 2019 Oct;106(4):726-733.

Myers AL, Kawedia JD, Nader A, Westin JR, Shank BR. A rare case of methotrexate and primaquine co-administration in a mantle cell lymphoma patient. J Clin Pharm Ther. 2019 Oct;44(5):800-804.

Kawedia JD, Kalariya N, Gulbis AM, Andersson BS, Myers AL. Pharmacokinetics: Unique Challenges in Blood Monitoring for Oncology Nurses. Clin J Oncol Nurs. 2019 Apr 1;23(2):191-196.

Nieto Y, Thall PF, Ma J, Valdez BC, Ahmed S, Anderlini P, Popat U, Jones RB, Shpall EJ, Hosing C, Qazilbash M, Kebriaei P, Alousi A, Timmons M, Gulbis A, Myers A, Oki Y, Fanale M, Dabaja B, Pinnix C, Milgrom S, Champlin R, Andersson BS.  Phase II Trial of High-Dose Gemcitabine/ Busulfan/ Melphalan with Autologous Stem Cell Transplantation for Primary Refractory or Poor-Risk Relapsed Hodgkin Lymphoma. Biol Blood Marrow Transplant. 2018 Aug;24(8):1602-1609.

Shank BR, Deaver M, Baker A, Myers AL, Zhang Y, Anderegg B, Bassett R, Westmoreland M.  Interdisciplinary Implementation of Tacrolimus Intravenous Standard Concentration in Hematopoietic Stem Cell Transplantation Recipients. J Oncol Pharm Pract 2018 Jul;24(5):365-370.

Myers AL, Ghose R, Kawedia JD, Champlin RC, Nieto Y, Andersson BS, Kramer MA. Clarifying busulfan metabolism and drug interactions to support new therapeutic drug monitoring strategies: a comprehensive review. Expert Opin Drug Metab Toxicol. 2017 Sep;13(9):901-923.

Myers AL, Zhang Y, Kawedia JD, Zhou X, Metcalfe MJ, Kramer MA, Dinney CPN, Kamat A. Solubilization and Stability of Mitomycin C Admixtures Prepared for Intravesical Administration.  Drugs R&D 2017;17(2): 297-304.   

A more comprehensive list of Dr. Myers’ publications can be found at:
https://www.ncbi.nlm.nih.gov/sites/myncbi/1TGifcT8QFj5u/bibliography/48455687/public/?sort=date&direction=ascending

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