Araba Adjei, PhD
Department of Pharmacology & Therapeutics
Roswell Park Cancer Institute
Elm and Carlton Streets
Buffalo NY USA 14263
Tel: 716 - 845 - 1192
Fax: 716 - 845 - 8281
E-mail: araba.adjei@roswellpark.org

Education

Ph. D., University of Alberta, Edmonton, Canada.
Research Scientist, Biomira Inc., Edmonton, Alberta, Canada.
Assistant Professor and Professional Assistant in Research (PAR), Dept. of Molecular Pharmacology & Experimental Therapeutics, Mayo Clinic/Mayo Foundation, Rochester, MN.               

Research Area/Interests

Pharmacogenetics of anticancer agents.
Integrating pharmacogenomics into clinical trials as an approach to individualized medicine.
Pharmacogenetics and ethnic variations in efficacy and toxicity of anticancer agents.

Program Description

Laboratory: This Translational Oncology Laboratory focuses on two major activities: (a) the pharmacogenetics of anti-cancer agents and (b) development of assays for correlative studies in conjunction with clinical trials in collaboration with clinician-investigators       

A.  Pharmacogenetics in cancer therapy aims to understand the role of inheritance in variations of drug response, either efficacy or toxicity. Because most anti-neoplastic drugs have narrow therapeutic indices, treatment with these drugs can sometimes result in significant life-threatening drug-induced toxicity. As well, therapeutic responses to these drugs are modest. It is therefore important to be able to predict which subset of the population will respond upfront to a drug in order to achieve better therapeutic effects and avoid unnecessary toxicity.

The laboratory’s activity focuses on identifying and understanding the role of genetic variations in response to drug therapy in ethnically diverse populations. We focus on resequencing target genes and proteins to identify functionally significant genetic variations that play roles in the pharmacokinetic (PK) and pharmacodynamic (PD) pathways of antineoplastic drugs. We also perform functional genomic studies to understand the underlying mechanism of those polymorphisms identified in the genes that encode the drug target and biotransformation enzymes and proteins. Additionally, we perform genotype-phenotype (clinical outcomes) correlative studies for clinical trials involving various disease sites in patients undergoing cancer treatment in RPCI.

These studies will provide a better understanding of the association of individual genetic variations with characteristics of a disease, with the ultimate aim of identifying genetic markers that will predict for drug response, efficacy or toxicity.

Ongoing Pharmacogenomic Projects

Identification of genetic variants, functional characterization and correlative studies  for drug biotransformation and target genes such as those related to Vitamin D, EGFR, VEGF, TS, RFC, IGF-1R and others in disease sites including lung, colorectal, liver, prostate, head and neck and breast cancers.  

B.    The other activity for the laboratory is to provide assays for correlative studies in conjunction with clinical trials in collaboration with clinician investigators*.  Correlative Study Activities

Selected Publications

Peng Y, Feng Q, Wilk D, Adjei AA, Salavaggione OE, Weinshilboum RM, Yee VC. Structural basis of substrate recognition in thiopurine s-methyltransferase. Biochemistry 2008; 47(23):6216-25. 

Adjei AA, Gaedigk A, Simon SD, Weinshilboum RM, Leeder JS.  Interindividual variability in acetaminophen sulfation by human fetal liver: Implications for pharmacogenetic investigations of drug-induced birth defects. Birth Defects Res A Clin Mol Teratol. 2008; 82(3):155-65.

Furimsky AM, Green CE, Hunt Sharp LE, Catz P, Adjei AA, Parman T, Kapetanovic IM, Weinshilboum RM, Iyer LV. Effect of Resveratrol on 17 'b-Estradiol Sulfation by Human Hepatic and Jejunal S9 and Recombinant SULT1E1. Drug Metabolism and Disposition 2008; 36: 129-136.

Hildebrandt M, Adjei A, Weinshilboum R, Johnson JA, Berlin DS, Klein TE, Altman RB. Very important pharmacogene summary: sulfotransferase 1A1. Pharmacogenet Genomics. 2009; 19(6):404-6.

Adjei AA, Mandrekar SJ, Dy GK, Molina JR, Adjei AA, Gandara D, Ziegler KL, Stella PJ, Rowland KM Schild SE and Zinner RG. A phase II trial of pemetrexed plus bevacizumab for second-line therapy of patients with advanced non-small cell lung cancer (NSCLC): An NCCTG and SWOG study. J Clin Oncol, 2009; 28(4):614-619.          

 * Contact Dr. Adjei for detailed information.