Screening Technologies Branch

The Developmental Therapeutics Program has pioneered new methods of screening to facilitate new drug discovery for cancer therapeutics. These methods began as relatively labor and resource intensive in vivo studies, and evolved into more sophisticated in vitro screens which presaged a movement by the pharmaceutical industry to rely on in vitro screens for early drug discovery. The assembly of a repository of donated chemical samples (National Service Center-"NSC") for screening purposes was critical as was the acquisition and curation of the Natural Products Repository collection. The NCI60 screen has served as both a discovery screen and more recently, as a service screen for researchers. The development of bioinformatics tools which allow productive mining of historic screening data also represents a major advance.

Presently, molecularly targeted screens are in development as cancer targets are identified and validated. Screening campaigns are underway and confirmed hits are evaluated for suitability as drug leads. Current efforts involve managing ongoing screening projects (NCI60, RAND, CCR-DCTD Joint Development Committee projects). Interactions include those with technical support contractors (SAIC), extramural investigators (RAND) as well as intramural (CCR). Screening Technologies Branch serves to interact between these constituencies to facilitate high quality drug discovery science.

Credentials

Michael Currens has worked for the NCI for more than 25 years. He received the B.S. from the University of Maryland, College Park (1977); the M.S. in biomedical Sciences (1984) from Hood College, Frederick, MD; and the Ph.D. in Pharmacology from the George Washington University (1996). Research interests include anticancer and antiviral drug discovery and development, circumventing drug resistance through novel target discovery.

Recent Publications

NCBI PubMed listing of publications by Michael Currens.

Dorjsuren D, Burnette A, Gray GN, Chen X, Zhu W, Roberts PE, Currens MJ, Shoemaker RH, Ricciardi RP, Sei S. Chemical library screen for novel inhibitors of Kaposi's sarcoma-associated herpesvirus processive DNA synthesis. Antiviral Res. 2006 Jan;69(1):9-23. Epub 2005 Nov 18.

Yang QE, Stephen AG, Adelsberger JW, Roberts PE, Zhu W, Currens MJ, Feng Y, Crise BJ, Gorelick RJ, Rein AR, Fisher RJ, Shoemaker RH, Sei S. Discovery of small-molecule human immunodeficiency virus type 1 entry inhibitors that target the gp120-binding domain of CD4. J Virol. 2005 May;79(10):6122-33.

Stephen AG, Worthy KM, Towler E, Mikovits JA, Sei S, Roberts P, Yang QE, Akee RK, Klausmeyer P, McCloud TG, Henderson L, Rein A, Covell DG, Currens M, Shoemaker RH, Fisher RJ. Identification of HIV-1 nucleocapsid protein: nucleic acid antagonists with cellular anti-HIV activity. Biochem Biophys Res Commun. 2002 Sep 6;296(5):1228-37.

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.

O'Keefe, B.R., Shenoy, S.R., Xie, D., Zhang, W., Muschik, J.M., Currens, M.J., Chaiken, I., Boyd, M.R. Analysis of the interaction between the HIV-inactivating protein cyanovirin-N and soluble forms of the envelope glycoproteins gp120 and gp41. Mol Pharmacol. 2000 Nov;58(5):982-92.

Charan, R.D., Munro, M.H., O'Keefe, B.R., Sowder, R.C. II, McKee, T.C., Currens, M.J., Pannell, L.K., Boyd, M.R. Isolation and characterization of Myrianthus holstii lectin, a potent HIV-1 inhibitory protein from the plant Myrianthus holstii(1). J Nat Prod. 2000 Aug;63(8):1170-4.

Cardellina, J.H., Fuller, R.W., Gamble, W.R., Westergaard, C.A., Boswell, J., Munro, M.H.G., Currens, M., Boyd, M.R. Evolving strategies for the selection, dereplication and prioritization of antitumor and HIV-Inhibitory natural products extracts. Bioassy Methods in Natural Product Research and Drug Development. Eds. Lars Bohlin and J.G. Bruhn, Kluwer Academic Publishers, The Netherlands, pp. 25-35, 1999.

Boyd, M.R., Gustafson, K.R., McMahon, J.B., Shoemaker, R.H., O'Keefe, B.R., Mori, T., Gulakowski, R.F., Wu, L., Rivera, M.I., Laurencot, C.M., Currens, M.J., Cardellina, J.H. 2nd, Buckheit, R.W. Jr., Nara, P.L., Pannell, L.K., Sowder, R.C. and Henderson, L.E. Discovery of cyanovirin-N, a novel human immunodeficiency virus-inactivating protein that binds viral surface envelope glycoprotein gp120: potential applications to microbicide development. Antimicrobial Agents Chemotherapy 41(7): 1521-30, 1997.

Currens, M.J., Mariner, J., McMahon, J.B., Boyd, M.R. Kinetic analysis of inhibition of HIV-1 reverse transcriptase by calanolide A. Jour. Pharm Exper Ther 279: 652-661, 1996.