Grover P Miller, PhD

Research Program: Cancer Therapeutics Faculty Rank: Professor Campus: University of Arkansas for Medical Sciences College: College of Medicine Department: Biochemistry & Molecular Biology

Cancer Research Interest

• Disease Site Focus: No Specific Disease Site
• Research Focus Area: Health Disparities, Treatment, Informatics, Detection, Carcinogenesis, Diagnosis/ Prognosis
• Type of Research: Basic
• Research Interest Statement: Integrating datamining, modeling and experimental approaches to develop safer targeted cancer therapeutics Recent advances in targeted cancer therapeutics boast superior health outcomes relative to traditional chemotherapy drugs; however, hepatotoxicity poses a major clinical concern for patients undergoing treatment with these revolutionary drugs. Drug metabolism plays a central role in toxicological mechanisms and thus, my research focuses on assessing clearance and bioactivation of drugs and subsequent biological, pharmacological and toxicological impacts on human health. In practice, my group integrates and leverages powerful analytical, biochemical, and computational tools to identify and quantitate small molecules including drugs present in biological samples and generated from metabolic reactions. Next, we correlate findings to biological activity and in vivo outcomes such as liver toxicity to establish toxicological mechanisms and the factors impacting those outcomes. Knowledge gained from these studies will aid in the design and use of safer targeted cancer therapeutics by minimizing associated toxicities that limit their use in the clinic.

Contact Information

• Email Address: MILLERGROVERP@UAMS.EDU
• Profiles Research Networking Software: View Profile

Active Grants

• NIH/Nat. Inst. of General Medical Sciences – 1R01GM14065
  “Systematic Discovery of Bioactivation-Associated Structural Alerts”
  Principal Investigator
  09/15/20 – 07/31/24

Publications

• Khojasteh SC, Argikar UA, Cheruzel L, [et al., including Miller GP]. Biotransformation research advances - 2022 year in review. Drug metabolism reviews. 2023:1-42. PMID: 37737116.
• Wang S, Argikar UA, Cheruzel L, [et al., including Miller GP]. Bioactivation and reactivity research advances - 2022 year in review‡. Drug metabolism reviews. 2023:1-34. PMID: 37608698.
• McGill MR, Kaufman YJ, LoBianco FV, [et al., including Miller GP]. The role of cytochrome P450 3A4-mediated metabolism in sorafenib and lapatinib hepatotoxicity. Livers. 2023 3(2):310-321. PMID: 38037613. PMCID: PMC10688230.
• Flynn NR, Miller GP, Swamidass SJ. Editorial: Advancements in computational studies of drug toxicity. Frontiers in pharmacology. 2023 14:1230409. PMID: 37346295. PMCID: PMC10280066.
• Crosby SV, Ahmed IY, Osborn LR, [et al., including Miller GP]. Similar 5F-APINACA Metabolism between CD-1 Mouse and Human Liver Microsomes Involves Different P450 Cytochromes. Metabolites. 2022 12(8). PMID: 36005645. PMCID: PMC9413144.
• Jackson KD, Argikar UA, Cho S, [et al., including Miller GP]. Bioactivation and reactivity research advances - 2021 year in review. Drug metabolism reviews. 2022:1-36. PMID: 35876116. PMCID: PMC10282953.
• Schleiff MA, Crosby S, Blue M, [et al., including Miller GP]. CYP2C9 and 3A4 play opposing roles in bioactivation and detoxification of diphenylamine NSAIDs. Biochemical pharmacology. 2021 194:114824. PMID: 34748821. PMCID: PMC8710044.
• Cui H, Carlson AS, Schleiff MA, [et al., including Miller GP]. 4-Methyl-1,2,3-Triazoles as N-Acetyl-Lysine Mimics Afford Potent BET Bromodomain Inhibitors with Improved Selectivity. Journal of medicinal chemistry. 2021. PMID: 34236185. PMCID: PMC8491147.
• Datta A, Flynn NR, Barnette DA, [et al., including Miller GP]. Machine learning liver-injuring drug interactions with non-steroidal anti-inflammatory drugs (NSAIDs) from a retrospective electronic health record (EHR) cohort. PLoS computational biology. 2021 17(7):e1009053. PMID: 34228716. PMCID: PMC8284671.
• Flynn NR, Ward MD, Schleiff MA, [et al., including Miller GP]. Bioactivation of Isoxazole-Containing Bromodomain and Extra-Terminal Domain (BET) Inhibitors. Metabolites. 2021 11(6). PMID: 34203690. PMCID: PMC8232216.
• Schleiff MA, Payakachat S, Schleiff BM, [et al., including Miller GP]. Impacts of diphenylamine NSAID halogenation on bioactivation risks. Toxicology. 2021:152832. PMID: 34107285. PMCID: PMC8513111.
• Khojasteh SC, Argikar UA, Driscoll JP, [et al., including Miller GP]. Novel advances in biotransformation and bioactivation research - 2020 year in review. Drug metabolism reviews. 2021:1-91. PMID: 33910427. PMCID: PMC8826528.
• Pouncey DL, Barnette DA, Sinnott RW, [et al., including Miller GP]. Discovery of Novel Reductive Elimination Pathway for 10-Hydroxywarfarin. Frontiers in pharmacology. 2021 12:805133. PMID: 35095511. PMCID: PMC8793337.
• Barnette DA, Schleiff MA, Datta A, [et al., including Miller GP]. Meloxicam methyl group determines enzyme specificity for thiazole bioactivation compared to sudoxicam. Toxicology letters. 2020 338:10-20. PMID: 33253783. PMCID: PMC7807415.
• Schleiff MA, Flynn NR, Payakachat S, [et al., including Miller GP]. Significance of Multiple Bioactivation Pathways for Meclofenamate as Revealed through Modeling and Reaction Kinetics. Drug metabolism and disposition: the biological fate of chemicals. 2020. PMID: 33239334. PMCID: PMC7841419.
• Pinson AO, Pouncey DL, Schleiff MA, [et al., including Miller GP]. Significance of Competing Metabolic Pathways for 5F-APINACA Based on Quantitative Kinetics. Molecules (Basel, Switzerland). 2020 25(20). PMID: 33092129. PMCID: PMC7587938.
• Khojasteh SC, Driscoll JP, Jackson KD, [et al., including Miller GP]. Novel advances in biotransformation and bioactivation research-2019 year in review(). Drug metabolism reviews. 2020 52(3):333-365. PMID: 32645275. PMCID: PMC10805366.
• Barnette DA, Schleiff MA, Osborn LR, [et al., including Miller GP]. Dual mechanisms suppress meloxicam bioactivation relative to sudoxicam. Toxicology. 2020 440:152478. PMID: 32437779. PMCID: PMC8716319.
• Barnette DA, Davis MA, Flynn N, [et al., including Miller GP]. Comprehensive kinetic and modeling analyses revealed CYP2C9 and 3A4 determine terbinafine metabolic clearance and bioactivation. Biochemical pharmacology. 2019 170:113661. PMID: 31605674. PMCID: PMC6905088.
• Matlock MK, Tambe A, Elliott-Higgins J, [et al., including Miller GP]. A Time-Embedding Network Models the Ontogeny of 23 Hepatic Drug Metabolizing Enzymes. Chemical research in toxicology. 2019 32(8):1707-1721. PMID: 31304741. PMCID: PMC6933754.
• Davis MA, Barnette DA, Flynn NR, [et al., including Miller GP]. CYP2C19 and 3A4 Dominate Metabolic Clearance and Bioactivation of Terbinafine Based on Computational and Experimental Approaches. Chemical research in toxicology. 2019 32(6):1151-1164. PMID: 30925039. PMCID: PMC6692898.
• Khojasteh SC, Bumpus NN, Driscoll JP, [et al., including Miller GP]. Biotransformation and bioactivation reactions - 2018 literature highlights. Drug metabolism reviews. 2019 51(2):121-161. PMID: 31170851.