Research Summary

In the last decade, Ronald E. Cannon, Ph.D. has focused on understanding the regulation of ATP-driven, xenobiotic efflux pumps (ABC transporters) at the blood-brain barrier. This barrier resides within the brain capillary endothelium and is a limiting factor in treating central nervous system (CNS) disorders, for instance, neurodegenerative diseases, epilepsy, brain cancer, and neuro-AIDS. P-glycoprotein, a drug efflux transporter, is a critical element of that barrier. High level of expression, luminal membrane location, broad specificity, and high transport potency make P-glycoprotein a primary obstacle to drug delivery to the brain and thus to CNS pharmacotherapy. More recently Cannon has expanded his focus to include other ABC transporters, MRPs and BCRP, and the blood-spinal cord barrier.

Cannon works in the Mechanistic Toxicology Branch within the NIEHS Division of Translational Toxicology (DTT). His work has importance because ABC transporters govern the uptake, distribution, and excretion of a large number of therapeutic drugs, environmental pollutants, and waste products of cellular metabolism, Cannon believes “we must have a thorough understanding of barrier transport mechanisms and the signals that modulate them to design better therapeutic protocols and predict toxic interactions.”

Selected Publications

1. Petriello MC, Mottaleb MA, Serio TC, Balyan B, Cave MC, Pavuk M, Birnbaum LS, Morris AJ. Serum concentrations of legacy and emerging per- and polyfluoroalkyl substances in the Anniston Community Health Surveys (ACHS I and ACHS II). Environ Int. 2022 Jan;158:106907. doi: 10.1016/j.envint.2021.106907. [Abstract Petriello MC, Mottaleb MA, Serio TC, Balyan B, Cave MC, Pavuk M, Birnbaum LS, Morris AJ. Serum concentrations of legacy and emerging per- and polyfluoroalkyl substances in the Anniston Community Health Surveys (ACHS I and ACHS II). Environ Int. 2022 Jan;158:106907. doi: 10.1016/j.envint.2021.106907.]
2. Emond C, DeVito MJ, Birnbaum LS. A PBPK model describing the pharmacokinetics of γ-HBCD exposure in mice. Toxicol Appl Pharmacol. 2021 Oct 1;428:115678. doi: 10.1016/j.taap.2021.115678. [Abstract Emond C, DeVito MJ, Birnbaum LS. A PBPK model describing the pharmacokinetics of γ-HBCD exposure in mice. Toxicol Appl Pharmacol. 2021 Oct 1;428:115678. doi: 10.1016/j.taap.2021.115678.]
3. Sinha BK, Perera L, Cannon RE. 2021. NCX-4040, a unique nitric oxide donor, induces reversal of drug-resistance in both ABCB1- and ABCG2-expressing multidrug human cancer cells. Cancers (Basel) 13(7):1680. [Abstract Sinha BK, Perera L, Cannon RE. 2021. NCX-4040, a unique nitric oxide donor, induces reversal of drug-resistance in both ABCB1- and ABCG2-expressing multidrug human cancer cells. Cancers (Basel) 13(7):1680.]
4. Cannon RE, Richards AC, Trexler AW, Juberg CT, Sinha B, Knudsen GA, Birnbaum LS. Effect of GenX on P-Glycoprotein, Breast Cancer Resistance Protein, and Multidrug Resistance-Associated Protein 2 at the Blood-Brain Barrier. Environ Health Perspect. 2020 Mar;128(3):37002. doi: 10.1289/EHP5884. Epub 2020 Mar 26. PMID: 32212926. [Abstract Cannon RE, Richards AC, Trexler AW, Juberg CT, Sinha B, Knudsen GA, Birnbaum LS. Effect of GenX on P-Glycoprotein, Breast Cancer Resistance Protein, and Multidrug Resistance-Associated Protein 2 at the Blood-Brain Barrier. Environ Health Perspect. 2020 Mar;128(3):37002. doi: 10.1289/EHP5884. Epub 2020 Mar 26. PMID: 32212926.] 
5. Sinha BK, Perera L, Cannon RE. Reversal of drug resistance by JS-K and nitric oxide in ABCB1- and ABCG2-expressing multi-drug resistant human tumor cells. Biomed Pharmacother 2019 doi: 10.1016/j.biopha.2019.109468 [Online 9 October 2019]. [Abstract Sinha BK, Perera L, Cannon RE. Reversal of drug resistance by JS-K and nitric oxide in ABCB1- and ABCG2-expressing multi-drug resistant human tumor cells. Biomed Pharmacother 2019 doi: 10.1016/j.biopha.2019.109468 [Online 9 October 2019].] 
6. Trexler AW, Knudsen GA, Nicklisch SCT, Birnbaum LS, Cannon RE. 2,4,6-Tribromophenol Exposure Decreases P-glycoprotein Transport at the Blood-Brain Barrier. Toxicological Sciences 2019 Jul 31. [Abstract Trexler AW, Knudsen GA, Nicklisch SCT, Birnbaum LS, Cannon RE. 2,4,6-Tribromophenol Exposure Decreases P-glycoprotein Transport at the Blood-Brain Barrier. Toxicological Sciences 2019 Jul 31.]
7. Cannon RE, Trexler AW, Knudsen GA, Evans RA, Birnbaum LS. Tetrabromobisphenol A (TBBPA) Alters ABC Transport at the Blood-Brain Barrier. Toxicological Sciences 2019 ():-. [Abstract Cannon RE, Trexler AW, Knudsen GA, Evans RA, Birnbaum LS. Tetrabromobisphenol A (TBBPA) Alters ABC Transport at the Blood-Brain Barrier. Toxicological Sciences 2019 ():-.]
8. Sinha BK, Bortner CD, Mason RP, Cannon RE. Nitric Oxide Reverses Drug Resistance by Inhibiting ATPase Activity of P-glycoprotein in Human Multi-drug Resistant Cancer Cells. Biochim Biophys Acta Gen Subj. 2018 Dec;1862(12):2806-2814. [Abstract Sinha BK, Bortner CD, Mason RP, Cannon RE. Nitric Oxide Reverses Drug Resistance by Inhibiting ATPase Activity of P-glycoprotein in Human Multi-drug Resistant Cancer Cells. Biochim Biophys Acta Gen Subj. 2018 Dec;1862(12):2806-2814.]
9. Banks DB, Chan GN, Evans RA, Miller DS, Cannon RE. Lysophosphatidic Acid and Amitriptyline Signal Through LPA1R to Reduce P-glycoprotein Transport at the Blood-brain Barrier. J Cereb Blood Flow Metab. 2018 May;38(5):857-868. [Abstract Banks DB, Chan GN, Evans RA, Miller DS, Cannon RE. Lysophosphatidic Acid and Amitriptyline Signal Through LPA1R to Reduce P-glycoprotein Transport at the Blood-brain Barrier. J Cereb Blood Flow Metab. 2018 May;38(5):857-868.]
10. Chan GN, Evans RA, Banks DB, Mesev EV, Miller DS, Cannon RE. Selective Induction of P-glycoprotein at the CNS Barriers during Symptomatic Stage of an ALS Animal Model. Neuroscience Letters 2017 639():103-111. [Abstract Chan GN, Evans RA, Banks DB, Mesev EV, Miller DS, Cannon RE. Selective Induction of P-glycoprotein at the CNS Barriers during Symptomatic Stage of an ALS Animal Model. Neuroscience Letters 2017 639():103-111.]