Professor

Anna Radominska-Pandya

Associate Member Winthrop P. Rockefeller Cancer Institute

Ph.D., Institute of Biochemistry and Biophysics, Polish Academy of Sciences, Warsaw, Poland

E-mailRadominskaAnna@uams.edu
Office: Office: (501) 603-5414 – Biomed 1 421G
Lab:  Biomed 1 B436
FAX:  (501)603-1146

Natural and Synthetic Cannabinoids. Our lab characterized the metabolism of natural cannabinoids using human hepatic and extrahepatic UDP-glucuronosyltransferases (UGTs). These studies were recently extended by investigations of synthetic cannabinoids (SCBs), also known as K2, Spice, and synthetic marijuana. SCBs are a growing problem in the United States; while there are more than 150 known chemical forms, new versions appear on the market every year. Although SCBs produce mind-altering effects by reacting with the same receptors responsible for marijuana’s psychoactive effects, they act on the brain in a much stronger way and have unpredictable effects that could lead to severe injury and death. Using natural cannabinoids as a control, our lab is actively involved in the investigation of the pharmacological effects of these new SCBs, examination of how the body processes these man-made drugs, and exploration of the effect that genetic polymorphisms have on their metabolism. Analysis of SCB metabolites led to the hypothesis that genetic variation could produce metabolism defects that cause severe effects. Further research could eventually lead to a way to identify people who can’t metabolize and excrete SCBs and thus have the highest risk for experiencing severe or even deadly outcomes from its use leading to the potential development of new clinical treatments to counteract those effects.

Role of human UGTs in cancer. Human UGTs are a class of enzymes that can metabolize a wide range of toxins and carcinogens and, therefore, play a critical role in the detoxification of these compounds. They also control the steady-state concentrations of ligands for nuclear receptors, which are essential for driving the proliferation of cancer cells. There is a correlation between the absence of UGT expression and cell proliferation. Comparisons of UGT expression levels in normal and cancer cells demonstrated a significant reduction in UGT mRNA in a number of tumor samples. It is hypothesized that down regulation of UGTs could be one of the basic events in neoplastic transformation. Transfection of genes encoding UGTs and natural compounds and their nanodelivery into breast and pancreatic cancer cells have been shown to decrease cell proliferation and stimulate apoptosis making it a potential method for the treatment of various cancers. These data allows us to propose a role for UGTs in preventing hormone-induced and/or chemical carcinogenesis.

 

Lab Members

Ryoichi Fujiwara, Ph.D.
Dr. Ryoichi Fujiwara

My work focuses on UDP-glucuronosyltransferase (UGT), a major drug-metabolizing enzyme. Specifically, I investigate extrahepatic tissues including gastrointestinal, skin, and brain. Studies of interest include:
• Humanized UGT1 mice, which were created by crossing Ugt1 knockout mice and human UGT1 transgenic mice, were especially useful to identify the importance of gastrointestinal UGT1A1 in bilirubin metabolism in the neonatal period.
• The role of UGTs in brain damage, brain development, neurotoxicity, oxidative stress, cardiovascular diseases, cancer, and many other biological functions.
• The involvement of glucuronidated metabolites in the development of adverse drug reactions.
• The development of a new diagnosing method that enables us to determine the probability of developing drug-induced toxicity in individual patients.
A full publication list can be found here.

 

Bailey Jackson, Research Technologist
Bailey Jackson

My background is in mechanical and materials engineering, including biomimetic compounds. The title of PhD dissertation is “Mechanical and Materials Characterization of Advanced Materials for Tissue Regeneration” from UALR.

Currently my work in UAMS focuses on Phase I (CYP450) and Phase II (UGTs) mediated metabolism of SCBs and natural cannabinoids. Current studies involve CYP inhibition with SCBs, polymorphism and possible drug interactions. I am especially interested in the recent SCBs added to market, and their toxicity, as well as comparisons with natural cannabinoids.

 

Selected Publications

Pinson A, Yarbrough AL, Bush JM, et al. Metabolism, CB1 cannabinoid receptor binding and in vivo activity of synthetic cannabinoid 5F-AKB48: Implications for toxicity [published online ahead of print, 2020 May 13]. Pharmacol Biochem Behav. 2020;195:172949. doi:10.1016/j.pbb.2020.172949 [Abstract]

Jones S, Yarbrough AL, Fantegrossi WE, et al. Identifying cytochrome P450s involved in oxidative metabolism of synthetic cannabinoid N-(adamantan-1-yl)-1-(5-fluoropentyl)-1H-indole-3-carboxamide (STS-135). Pharmacol Res Perspect. 2020;8(1):e00561. doi:10.1002/prp2.561 [Abstract]

Jones S, Yarbrough AL, Shoeib A, et al. Enzymatic analysis of glucuronidation of synthetic cannabinoid 1-naphthyl 1-(4-fluorobenzyl)-1H-indole-3-carboxylate (FDU-PB-22). Xenobiotica. 2019;49(12):1388-1395. doi:10.1080/00498254.2019.1580403 [Abstract]

Wilson CD, Tai S, Ewing L, et al. Convulsant Effects of Abused Synthetic Cannabinoids JWH-018 and 5F-AB-PINACA Are Mediated by Agonist Actions at CB1 Receptors in Mice. J Pharmacol Exp Ther. 2019;368(2):146-156. doi:10.1124/jpet.118.251157 [Abstract]

Hutchison RD, Ford BM, Franks LN, et al. Atypical Pharmacodynamic Properties and Metabolic Profile of the Abused Synthetic Cannabinoid AB-PINACA: Potential Contribution to Pronounced Adverse Effects Relative to Δ9-THC. Front Pharmacol. 2018;9:1084. Published 2018 Sep 26. doi:10.3389/fphar.2018.01084 [Abstract]

Patton AL, Seely KA, Yarbrough AL, Fantegrossi W, James LP, McCain KR, Fujiwara R, Prather PL, Moran JH, Radominska-Pandya A. Altered metabolism of synthetic cannabinoid JWH-018 by human cytochrome P450 2C9 and variants. Biochem Biophys Res Commun. 2018 Apr 6;498(3):597-602.  [Abstract]

Read a more comprehensive list of my publications.