Genomics of drug response.

Relative expression of gene or protein targets measured in the 60 cell lines of the screen are correlated with patterns of drug response in an effort to identify potential effectors of these targets. Research in the laboratory centers around identifying changes in gene expression patterns in sensitive and resistant cell lines following drug treatment using microarray technology and Serial Analysis of Gene Expression (SAGE). Non-molecular based strategies focus on in vitro evaluation of possible adverse or advantageous interactions between potential clinical drug combinations.

Collaborations: Dr. Monks is a coordinator for the molecular target program of DTP which seeks to measure important protein and gene expression patterns in the 60 cell lines of the drug screen, and usually involves collaborators who are experts in particular molecular targets. Target expression patterns are correlated with thousands of drug response patterns in the database. These studies allow for detailed molecular characterization and comparison within a large group of standardized cell lines. Moreover, the resulting correlative analyses may identify individual compounds, or groups of compounds whose activity is contingent on expression of that particular protein or gene.

Credentials

Dr. Anne Monks was educated in Great Britain and received her honors degree in Applied Biology from Hatfield University in 1975. She studied for her Ph.D. at the Clinical Pharmacology Department of St. Bartholomews Hospital and was awarded the degree in Clinical Pharmacology from London University in 1979. Dr. Monks became a Fogarty Fellow from 1979-1982 in the Laboratory of Chemical Pharmacology, DTP, NCI, then became a Visiting Associate in the same laboratory until 1985. During her tenure at NIH she investigated the homeostatic control of circulating nucleosides and their effect on clinical antimetabolites using the rat liver perfusion model. In 1995, Dr. Monks joined the NCI-Frederick Cancer and Research Facility as a contractor (currently SAIC-Frederick, http://www.saic.com/) dedicated to support the Developmental Therapeutics Program's newly proposed 'In Vitro Anti-Cancer Drug Screening Program'. Her group's current research is directed towards characterization of potential molecular targets for cancer drug therapy, and gene expression changes in response to drug treatment.

Recent Publications

NCBI PubMed listing of publications by Anne Monks.

Scheffer GL, de Jong MC, Monks A, Flens MJ, Hose CD, Izquierdo MA, Shoemaker RH, Scheper RJ. Increased expression of beta 2-microglobulin in multidrug-resistant tumour cells. Br J Cancer. 2002 Jun 17;86(12):1943-50.

Xu Z, Chen ZP, Malapetsa A, Alaoui-Jamali M, Bergeron J, Monks A, Myers TG, Mohr G, Sausville EA, Scudiero DA, Aloyz R, Panasci LC. DNA repair protein levels vis-a-vis anticancer drug resistance in the human tumor cell lines of the National Cancer Institute drug screening program. Anticancer Drugs. 2002 Jun;13(5):511-9.

Shoemaker RH, Scudiero DA, Melillo G, Currens MJ, Monks AP, Rabow AA, Covell DG, Sausville EA. Application of high-throughput, molecular-targeted screening to anticancer drug discovery. Curr Top Med Chem. 2002 Mar;2(3):229-46.

Krajewska M, Zapata JM, Meinhold-Heerlein I, Hedayat H, Monks A, Bettendorf H, Shabaik A, Bubendorf L, Kallioniemi OP, Kim H, Reifenberger G, Reed JC, Krajewski S. Expression of Bcl-2 family member Bid in normal and malignant tissues. Neoplasia. 2002 Mar-Apr;4(2): 129-40.

Silva GL, Cui B, Chavez D, You M, Chai HB, Rasoanaivo P, Lynn SM, O'Neill MJ, Lewis JA, Besterman JM, Monks A, Farnsworth NR, Cordell GA, Pezzuto JM, Kinghorn AD. Modulation of the multidrug-resistance phenotype by new tropane alkaloid aromatic esters from Erythroxylum pervillei. J Nat Prod. 2001 Dec;64(12):1514-20.

Lam LT, Pickeral OK, Peng AC, Rosenwald A, Hurt EM, Giltnane JM, Averett LM, Zhao H, Davis RE, Sathyamoorthy M, Wahl LM, Harris ED, Mikovits JA, Monks AP, Hollingshead MG, Sausville EA, Staudt LM. Genomic-scale measurement of mRNA turnover and the mechanisms of action of the anti-cancer drug flavopiridol. Genome Biol. 2001;2(10):RESEARCH0041.

Grem JL, Danenberg KD, Behan K, Parr A, Young L, Danenberg PV, Nguyen D, Drake J, Monks A, Allegra CJ. Thymidine kinase, thymidylate synthase, and dihydropyrimidine dehydrogenase profiles of cell lines of the National Cancer Institute's Anticancer Drug Screen. Clin Cancer Res. 2001 Apr;7(4):999-1009.

Meinhold-Heerlein I, Stenner-Liewen F, Liewen H, Kitada S, Krajewska M, Krajewski S, Zapata JM, Monks A, Scudiero DA, Bauknecht T, Reed JC. Expression and potential role of Fas-associated phosphatase-1 in ovarian cancer. Am J Pathol. 2001 Apr;158(4):1335-44.

Yu LJ, Matias J, Scudiero DA, Hite KM, Monks A, Sausville EA, Waxman DJ. P450 enzyme expression patterns in the NCI human tumor cell line panel. Drug Metab Dispos. 2001 Mar;29(3):304-12.