Joyce Goldstein, Ph.D.

Scientist Emeritus

Toxicology & Pharmacology Laboratory / Human Metabolism Group

NIEHS

A323 Rall Building
111 T W Alexander Dr
Research Triangle Park, NC 27709

919-541-4495

joyce.goldstein@nih.gov

Research Topics

Dr. Goldstein is an expert on the human cytochrome P450 enzymes in particular members of the CYP2C subfamily. She cloned and identified two of the four members. She identified the first polymorphisms in CYP2C19, which metabolizes Mephenytoin, omeprazole and other proton pump inhibitors, as well as valium and clopidogrel (Plavix). She also identified the most important CYP2C9 polymorphism, CYP2C9*3 which alters the affinity for antidiabetic drugs, warfarin (coumadin), phenytoin, anti-inflammatory drugs and many other drugs. She has a patent on the CYP2C19 *2 polymorphism.

Her recent work concerns the regulation of the CYP2 genes by various receptors such as the constitutive androstane receptor (CAR), Pregnane X receptor (PXR), hepatic nuclear factor 4α (HNF4) and their posttranslational regulation by microRNAs. Cross-talk between HNF4 and CAR has been attributed to coactivators such as NCOA6 and Med25, part of the mediator complex. The role of epigenetics in the regulation of CYP2C9 is being investigated. Med25 has been found to be the variable part of the mediator complex, which brings RNA pol II to HNF4 sites of select sets of HNF4-inducible genes.

Biography

Dr. Goldstein has been a principal investigator since 1977 at the National Institute of Environmental Health Sciences and has been a member of the Senior Biomedical Research Service. She was selected one of ISI's most cited pharmacologists. She is a member of the Faculty of 1000, and serves on numerous editorial boards. She is a diplomat of the American Board of Toxicology.

Selected Publications

  1. Langaee TY, Zhu HJ, Wang X, El Rouby N, Markowitz JS, Goldstein JA, Johnson JA. The influence of the CYP2C19*10 allele on clopidogrel activation and CYP2C19*2 genotyping. Pharmacogenet Genomics. 2014;24(8):381-6.

  2. Makia NL, Surapureddi S, Monostory K, Prough RA, Goldstein JA. Regulation of human CYP2C9 expression by electrophilic stress involves activator protein 1 activation and DNA looping. Mol Pharmacol. 2014;86(2):125-37.

  3. Shi Z, Yang W, Goldstein JA, Zhang SY. Med25 is required for estrogen receptor alpha (ERα)-mediated regulation of human CYP2C9 expression. Biochem Pharmacol. 2014;90(4):425-31.

  4. Zhang SY, Surapureddi S, Coulter S, Ferguson SS, Goldstein JA. Human CYP2C8 is post-transcriptionally regulated by microRNAs 103 and 107 in human liver. Mol Pharmacol. 2012;82(3):529-40.


This page was last updated on August 20th, 2013