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Developmental Therapeutics Program (DTP)
Last Updated: 04/02/15

Functional Genomics Laboratory at
the Frederick National Laboratories
for Cancer Research

The Functional Genomics Laboratory provides genomic techniques, including gene expression microarrays, exon arrays, microRNA arrays, TaqMan® real-time polymerase chain reaction (RT-PCR), reporter gene assays, multiplexing gene assays, RNA interference, methylation assays, metabolic analyses, elucidation of protein expression, immunofluorescence and anchorage dependent and independent growth assays plus others as tools to identify potential drug targets and to determine the role of selected genes in the mechanisms of drug action and cellular responses to stressors. These methods are useful to probe for insights into the mechanisms of action of novel agents, as well as for detailed analyses of specific cells. The functional genomics lab is a resource that is widely tapped into by collaborators within NCI as well as external investigators.1-8 The FGL has taken on large-scale projects including profiling of gene expression changes in the NCI60 cell line panel following exposure to 15 anticancer agents with varied mechanisms of action after 2, 6 and 24 hours exposure at two concentrations. Analyses of these data may elucidate cellular responses to the drugs and potentially lead to new rationale drug combinations or elucidate new points of vulnerability in the malignant cells which can be targeted with therapeutic agents. FGL is currently involved in the full genomic characterization (gene expression, exon expression, mutations, deletions, amplifications, microRNAs and other non-coding RNAs) of the human sarcoma lines and SCLC lines with a goal of identifying potential drug targets in normal and mutant proteins. The FGL is headed by Dr. Anne Monks who has >20 years experience at NCI.

References

  1. Kummar S, Kinders R, Gutierrez ME, Rubinstein L, Parchment RE, Phillips LR, Ji J, Monks A, low JA, Chen A, Murgo AJ, Collins J, Steinberg SM, Eliopoulos H, Giranda VL, Gordon G, Helman L, Wiltrout R, Tomaszewski JE, Doroshow JH. Phase o clinical trial of the poly (ADP-ribose) polymerase inhibitor ABT-888 in patients with advanced malignancies. J Clin Oncol 2009; 2705-11.
  2. Fer ND, Shoemaker RH, Monks A. Adaphostin toxicity in a sensitive non-small cell lung cancer model is mediated through Nrf2 signaling and heme oxygenase 1. J Exp Clin Cancer Res 2010; 29: 91-8.
  3. Muus U, Hose C, Yao W, Kosalkowska-Cholody T, Farnsworth D, Dyba M, Lountos GT, Waugh DS, Monks A, Burke TR, Michejda CJ. Bioorg Med Chem 2010; 18: 4535-41.
  4. Jobson AG, Lountos GT, Lorenzi PL, Connelly J, Cerna D, Tropea JE, Onda A, Zoppoli G, Kondapaka S, Zhang G, Caplen NJ, Cardellina JH, Yoo SS, Monks A, Self C, Waugh DS, Shoemaker RH, Pommier Y. Cellular inhibition of checkpoint kinase 2 (Chk2) and potentiation of campothecins and radiation by the novel Chk2 inhibitor PV1019 [7-nitro-1H-indole-2-carboxylic acid {4-[1-(guanidinohydrazone)-ethyl]-phenyl}-amide]. J Pharmacol Exp Therap 2009; 331: 816-26.
  5. Monks A, Hose C, Pezzoli P, Kondapaka S, Vasant G, Petersen KD, Sehested M, Monteforte J, Shoemaker RH. Gene expression-signature of belinostat in cell lines is specific for histone deacetylase inhibitor treatment, with corresponding signature in xenografts. Anticancer Drugs 2009; 20: 682-92.
  6. Kosakowska-Cholody T, Cholody WM, Hariprakasha HK, Monks A, Kar S, Wang M, Michejda CJ, Carr BI. Growth inhibition of hepatocellular carcinoma cells in vitro and in vivo by the 8-methoxy analog of WMC79. Cancer Chemotherap Pharmacol 2009; 63: 769-78.
  7. Martinez JM, Sali T, Okazaki R, Anna C, Hollingshead M, Hose C, Monks A, Walker NJ, Baek SJ, Eling TE. Drug-induced expression of nonsteroidal anti-inflammatory drug-activated gene/macrophage inhibitory cytokine-1/prostate-derived factor, a putative suppressor, inhibits tumor growth.
  8. Wallqvist A, Connelly J, Sausville EA, Covell DG, Monks A. Differential gene expression as a potential classifier of 2-(4-amino-3-methylphenyl)-5-fluorobenzothiazole-sensitive and -insensitive cell lines. Molec Pharmcol 2006; 69: 737-48.

About the Branch Chief

Dr. Mary K. Wolpert, Ph.D. Dr. Beverly A. Teicher PhD is Chief of the Molecular Pharmaco-logy Branch at NCI, a position that she assumed in early 2011. One focus of the Molecular Pharmacology Branch is target and drug discovery for rare and recalcitrant cancers such as sarcoma and small cell lung cancer. Dr. Teicher completed a PhD in Bioorganic Chemistry at the Johns Hopkins University and postdoctoral training at Yale University School of Medicine. More…