University of Arkansas, 2002
The overall goal of our research is to develop medications to treat chronic and acute methamphetamine (METH) abuse. We have taken several approaches toward accomplishing this goal in my laboratory. In the first project we combined antibody therapy and nanotechnology to generate an adaptable range of anti-METH medications (dendribodies) that have applicability to important therapeutic treatment (e.g., a short-acting medication for overdose and a long-acting, low volume of distribution medication needed for chronic treatment of addiction). These studies provided the first detailed information on the necessary design features and molecular principles required to create an advanced new generation of novel antibody-nanoparticle antagonists for the treatment of drug abuse.
We have also utilized adeno-associated virus (AAV) particles to deliver genes encoding high-affinity anti-METH antibody fragments discovered by our research team. We envision that AAV-mediated gene transfer could be used to persistently deliver these purposely designed antibody-based medications with precise specificity and high affinity for METH.
In a current project, we hypothesize that inhibition of critical inflammatory pathways can mitigate METH-induced pro-inflammatory transcriptional, epigenetic, and proteomic changes in brain regions associated with reward and addiction in rat models of MUD. Mitigating these METH-induced inflammatory responses during METH self-administration and METH abstinence could reduce METH self-administration reinstatement in rats.
Recent Research Support
- R01 DA039195-01 NIH (Co-I) (04/15/15 – 03/31/19)
“Pharmacology and Therapy for MDPV and alpha-PVP Like Drugs of Abuse”
- NIH/NIDAR01 DA036600 (PI) (07/01/14 – 06/30/18)
“Gene therapy for the treatment of methamphetamine abuse”
- R21 DA041822-01 (Co-I) (07/01/16 – 06/30/18)
Technology for identification of epiproteomes in tissue samples
- NIH/NIDA R01 DA026423 (PI (04/01/09 – 03/31/13)
“Antibody-nanoparticle conjugates for the treatment of methamphetamine abuse”
- NIH/NIDA NRSA Postdoctoral Fellowship F32 DA018039 (PI) (2004 – 2007)
“Single Chain Antibody Medications for(+)METH Abuse”
- Graw S, Tang J, Zafar MK, Byrd AK, Bolden C, Peterson EC, and Byrum SD (2020) proteiNorm – A User-Friendly Tool for Normalization and Analysis of TMT and Label-Free Protein Quantification. ACS Omega, doi: 10.1021/acsomega.0c02564.
- McClenahan MJ, Kormos CM, Gunnell M, Hambuchen MD, Lamb P, Carroll FI, Lewin AH, Peterson EC, and Owens SM. (2020) Design, Synthesis and Biological Evaluation of a Bi-specific Vaccine Against α-Pyrrolidinovalerophenone (α-PVP) and 3,4-Methylenedioxypyrovalerone (MDPV) in Rats. Psychopharmacology 237:2613–2620
- Hay CE, LE Ewing, MD Hambuchen, JC Zintner, SC Small, CT Bolden, WE Fantegrossi, P Margaritis, SM Owens, EC Peterson (2020) The development and characterization of an scFv-Fc fusion based gene therapy to reduce the psychostimulant effects of methamphetamine abuse J Pharmacol Exp Ther 374:16-23
- Hay, CE, Gonzalez III, GA, Ewing, LE, Reichard, EE, Hambuchen MD, Nanaware-Kharade, N, Alam, S, Bolden, CT, Owens, SM, Margaritis, P, EC Peterson. Development and Testing of AAV-delivered Single-Chain Variable Fragments for the Treatment of Methamphetamine Abuse. In press – PLOS ONE. 2018
- Reichard E, Nanaware-Kharade N, Gonzalez GA, Thakkar S, Owens SM, Peterson EC. PEGylation of a High-Affinity Anti-(+)Methamphetamine Single Chain Antibody Fragment Extends Functional Half-Life by Reducing Clearance. Pharmaceutical Research. Epub. 2016. PMID: 27620175
- Peterson EC, Ewing LE. Nanomedicine: Going small to beat the high. News and Views, Nat Nanotechnol. 11(7):580–581, 2016. PMID: 26974956
- Nanaware-Kharade NS, Thakkar S, Gonzalez III GA, Peterson EC. A Nanotechnology-Based Platform for Extending the Pharmacokinetic and Binding Properties of Anti-methamphetamine Antibody Fragments. Sci Rep. 5:12060, 2015. PMID: 26159352
- Peterson EC, Hambuchen MD, Tawney RL, Gunnell MG, Cowell JL, Lay J, Blough BE, Carroll FI, Owens SM. Simple radiometric method for accurately quantitating epitope densities of hapten-protein conjugates with sulfhydryl linkages. Bioconjugate Chem. 25(12):2112-2115, 2014. PMID:25426820
- Shakkar S, Nanaware-Kharade N, Celikel R, Peterson EC, Varughese KI. Affinity improvement of a therapeutic antibody to methamphetamine and amphetamine through structure-based antibody engineering. Sci Rep. 14:4:3673, 2014. PMID: 24419156
- Peterson EC, WB Gentry, SM Owens. Customizing Monoclonal Antibodies for the Treatment of Methamphetamine Abuse: Current and Future Applications. Adv Pharmacol. 69:107-27, 2014. PMID: 24484976
- Peterson EC, Celikel R, Gokulan K, Varughese KI. Structure of a therapeutic single chain antibody fragment: oligomerization and binding of metabolites. PLoS One. 5;8(12):e82690, 2013. PMID: 24349338
- Nanaware-Kharade N, Gonzalez GA III, Lay JO Jr, Hendrickson HP, Peterson EC. (2012) Therapeutic anti-methamphetamine antibody fragment-nanoparticle conjugates: synthesis and in vitro characterization Bioconj Chem. 19;23(9):1864-72, 2012. PMID: 22873701
- Dekeyser JG, Laurenzana EM, Peterson EC, Chen T, Omiecinski CJ. Selective phthalate activation of naturally occurring human constitutive androstane receptor splice variants and the pregnane X receptor. Toxicol Sci. 120(2):381-91, 2011. PMID: 21227907, Selected as paper of the year by the Society of Toxicology
- Carroll FI, Blough BE, Pidaparthi RR, Abraham P, Gong PK, Deng L, Huang X, Gunnell M, Lay JO, Peterson EC, Owens SM. Synthesis of mercapto-(+)- methamphetamine haptens and their use for obtaining improved epitope density on (+)-methamphetamine conjugate vaccines. J Med Chem. 54(14):5221-8, 2011. PMID: 21682289
- Owens SM, Atchley WT, Hambuchen MD, Peterson EC, Gentry WB. Monoclonal antibodies as pharmacokinetic antagonists for the treatment of (+)-methamphetamine addiction. CNS Neurol Disord Drug Targets. 10: 892-898, 2011. PMID: 22229314