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 perform gene resequencing and functional genomic studies to understand the underlying mechanism of polymorphisms identified in genes with disease relevance that encode drug target enzymes, as well as proteins which play roles in pharmacokinetic (PK) and pharmacodynamic (PD) pathways of antineoplastic drugs. Whenever possible, observations from functional genomic studies (performed in cell culture) will be confirmed by genotype-phenotype correlation analysis performed with human tissue biopsy samples. Information from these studies will be translated for application into clinical trials in RPCI.

These studies will provide a better understanding of associations of individual ethnic variations in genes with characteristics of a disease and response to the anticancer drug treatment.

Ongoing Projects

CYP24A1 Resequencing (as part of the Vitamin D pathway genes resequencing project): CYP24A1 is the key enzyme in the catabolism of vitamin D. As an initial step in the comprehensive evaluation of polymorphisms in vitamin D pathway genes and their influence on the role of vitamin D in carcinogenesis, we are resequencing CYP24A1 in Caucasians, African-Americans and Mexican-Americans and functionally characterizing the observed ethnically diverse genetic variations.

EGFR Pharmacogenomics:Functional Characterization of EGFR variant allozymes.

Pemetrexed Pharmacogenomics: Correlative studies in a series of Clinical Trials with Pemetrexed

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

Gene Resequencing and functional genomics:

Adjei, Araba A., Thomae, Bianca A., Prondzinski, Janel L., Eckloff, Bruce, Weiben, Eric and Weinshilboum, Richard M.: Human Estrogen Sulfotransferase (SULT1E1) Pharmacogenomics: Gene Resequencing and Functional Genomics. British Journal of Pharmacology 139:1373-1382, 2003.

Ma CX, Adjei AA, Salavaggione OE, Coronel J, Pelleymounter L, Wang L, Eckloff BW, Schaid D, Wieben ED, Adjei AA, Weinshilboum RM. Human aromatase: gene resequencing and functional genomics. Cancer Res. 65(23):11071-82, 2005.

Leil TA, Endo C, Adjei AA, Dy GK, Salavaggione OE, Reid JR, Ames MM,   Adjei AA.  Identification and characterization of genetic variation in the folylpolyglutamate synthase gene. Cancer Res; 67(18):8772-82, 2007.

Pharmcogenetics and Clinical Studies

Matthew Goetz, David Toft, Joel Reid, Matthew Ames, Bridget Stensgard, Stephanie Safgren, Araba A. Adjei , Jeff Sloan, Pamela Atherton, Vlad Vasile, Sandra Salazaar, Alex Adjei, Gary Croghan, and Charles Erlichman. A Phase I Trial of 17-Allylamino-Geldanamycin in Patients with Advanced Cancer. Journal of Clinical Oncology 23: 1078-1087, 2005.

Yan Jin., Zeruesenay Desta., Vered Stearns, Bryan Ward, Herbert Ho, Kyung-Hoon Lee, Todd Skaar, Anna Maria Storniolo, Lang Li, Adjei Araba, Rebecca Blanchard, Anne Nguyen, Lynda Ullmer, Jill Hayden, Suzanne Lemler, Richard M. Weinshilboum, James M. Rae, Daniel F. Hayes, David A. Flockhart: CYP2D6 Genotype, Antidepressant Use, and Tamoxifen Metabolism During Adjuvant Breast Cancer Treatment. Journal of the National Cancer Institute 97:30-39, 2005.

Sellers TA, Schildkraut JM, Pankratz VS, Vierkant RA, Fredericksen ZS, Olson JE, Cunningham J, Taylor W, Liebow M, McPherson C, Hartmann LC, Pal T, Adjei AA. Estrogen bioactivation, genetic polymorphisms, and ovarian cancer. Cancer Epidemiol. Biomarkers Prev. 14:2536-43, 2005. 

Araba A. Adjei, Andrea Gaedigk, Stephen D. Simon, Richard M. Weinshilboum and J. Steven Leeder. 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 Jan 29 [Epub ahead of print]  PMID: 18232020 [PubMed - as supplied by publisher]

 * Contact Dr. Adjei for detailed information.