Army Malaria Institute -
Walter Reed Army Institute of Research (WRAIR) Laboratory
(US Army Detachment)

Mission

To conduct research that supports the discovery of new antimalarial drugs for the treatment and protection of Australian and United States military personnel against malaria infections. In support of this mission the WRAIR Lab uses and develops tools ranging from molecular biology to clinical drug studies. The WRAIR Lab works closely with the Departments of Drug Resistance and Diagnostics (DRD) and Drug Evaluation (DE) in all studies.

Department Structure

Exchange officers from the Walter Reed Army Institute of Research (WRAIR) are part of the Engineer and Scientist Exchange Program (ESEP) between Australia and the United States. The WRAIR lab collaborates closely with DRD and DE Departments at AMI, as well as the Division of Experimental Therapeutics, WRAIR.

Current Research Projects

1. Discovery of selective inhibitors of Pfmrk, a malarial protein kinase, as novel antimalarial agents. (Collaboration with WRAIR and University of Northern Colarado.)
2. Discovery of selective inhibitors of malarial fatty acid biosynthesis enzymes. (Collaboration with WRAIR, John Hopkins University, Portland State University and University of Melbourne.)
3. Develop new assay methods and analysis parameters to evaluate slow acting and stage specific antimalarials. (Collaboration with DE.)
4. Investigate growth conditions of in vitro drug assays to better understand and correlate in vitro and in vivo efficacy data. (Collaboration with DE, WRAIR and John Hopkins University.)
5. Study cell cycle control mechanisms within Plasomodium falciparum to identify and exploit novel drug targets. (Collaboration with WRAIR, DRD and DE.)
6. Identify a role of protein kinases in artemisinin induced dormancy within Plasomodium falciparum. (Colaboration with DRD.)
7. Discovery of natural products as potent antimalarial agents. (Collaboration with DE and University of Nairobi.)
8. Assess malaria drug resistance within the South Pacific region. (Colaboration with DRD.)

    

Collaborators

Australian

1. Queensland Institute of Medical Research (QIMR)
2. University of Melbourne
3. University of Queensland

International

1. Division of Experimental Therapeutics, Walter Reed Army Institute of Research, USA.
2. Malaria Research Institute, John Hopkins University
3. University of Northern Colorado
4. Portland State University
5. World Health Organization
6. University of Nairobi, Kenya
7. United States Army Medical Research Unit - Kenya

Publications

Woodard, C. L., S. M. Keenan; L. A. Gerena, W. J. Welsh, J. A. Geyer, N. C. Waters. 2007. Evaluation of broad spectrum protein kinase inhibitors to probe the architecture of the malarial cyclin dependent protein kinase Pfmrk. Bioorganic & Medicinal Chemistry Letters. 17: 4961-4966. 

Lanteri, C. A., J. D. Johnson, N. C. Waters. 2007. Recent Advances in Malaria Drug Discovery. Recent Patents Anti-Infective Drug Discovery. 2:95-114.

Johnson, J. D., R. A. Dennull, L. Gerena, M. Lopez-Sanchez, N. E. Roncal, N. C. Waters. 2007. Assessment and Continued Validation of the MSF Assay for Use in Malaria Drug Screening. Antimicrob Agents Chemother. 51(6):1926-1933.

Alhamadsheh, M. M., N. C. Waters, D. P. Huddler, M. Kreishman-Deitrick, G. Florova, K. A. Reynolds. 2006. Synthesis and biological evaluation of thiazolidine-2-one 1,1-dioxide as inhibitors of Escherichia coli β-ketoacyl-ACP-synthase III (FabH). Bioorganic & Medicinal Chemistry Letters. 17(4):879-83.

Abosl, A. O., E. Mbukwa, B. H. Raserok, R. .R. Majinda, A. Yenesew, J. O. Midiwo, H. Akala, P. Liyala, N. C. Waters. 2006. Vangueria infausta root bark: in vivo and in vitro antiplasmodial activity.Br J Biomed Sci. 2006;63(3):129-33.

Chen, Y., D. Jirage, D. Caridha, A. K. Kathcart, E. Cortes, J. A. Geyer, S. T. Prigge, and N. C. Waters. 2006. Identification of an effector protein and gain-of-function mutants that activate Pfmrk, a malarial cyclin dependent protein kinase. Mol. Biochem. Parasit. 149:48-57.

Andayi, A.W., A. Yenesew,  S. Derese, J. O. Midiwo, P. M. Gitu, O. J. Jondiko, H. Akala, P. Liyala, J. Wangui, N. C. Waters, M. Heydenreich, and M. G. Peter. 2006. Antiplasmodial Flavonoids from Erythrina sacleuxii. Planta Med; 72(2):187-9.

Geyer, J. A., S. T. Prigge, and N. C. Waters. 2005. Targeting malaria with specific CDK inhibitors. Biochim Biophys Acta. 1754(2005):160-170.

Lu, J. Z., P. J. Lee, N. C. Waters, and S. T.  Prigge. 2005. Fatty Acid synthesis as a target for antimalarial drug discovery. Comb. Chem. High Throughput Screen; 8(1):15-26.

Waters, N. C., S. M. Keenan, J. A. Geyer, W. J. Welsh, and S. T. Prigge. 2005. Rational inhibitor design and iterative screening in the identification of selective plasmodial cyclin dependent kinase inhibitors. Comb. Chem. High Throughput Screen. 8(1):27-38.

Yenesew, A, M. Induli,  S. Derese, J. O. Midiwo, M. Heydenreich, M. G. Peter, H. Akala, J. Wangui, P. Liyala, and N. C. Waters. 2004. Anti-plasmodial flavonoids from the stem bark of Erythrina abyssinica. Phytochemistry. 65(22):3029-32.

Bhattacharjee, A. K., J. A  Geyer, C. L. Woodard, A. K. Kathcart, D. A. Nichols, S. T. Prigge, Z. Li,  B. T. Mott, and N. C. Waters. 2004. A Three-Dimensional in Silico Pharmacophore Model for Inhibition of Plasmodium falciparum Cyclin-Dependent Kinases and Discovery of Different Classes of Novel Pfmrk Specific Inhibitors. J. Med. Chem. 47(22):5418-5426.

Mbaisi, Abigael, P. Liyala, F. Eyase, R. Achilla, H. Akala, J. Wangui, J. Mwangi, F. Osuna,U. Fazal, B. Smoak, D. G. Shanks, J. Davis, D. E. Kyle, R. L. Coldren, C. Mason, and N. C. Waters. 2004. Drug susceptibility and genetic evaluation of  Plasmodium falciparum isolates obtained in four distinct geographical regions of Kenya. Antimicrob Agents Chemother. 48(9):3598-3601.

Waters, N. C., G. S. Dow, and M. P. Kozar. 2004. Antimalarial compound identification and design: advances in the patent literature, 2000-2003. Expert. Opin. Therap. Patents. 14(8):1125-1138.

Woodard, C, L., Z. Li, A. Kathcart, J. Terrell, L. Gerena, M.Lopez-Sanchez, D. E. Kyle, A. Bhattacharjee, D. Nichols, W. Ellis, S. T. Prigge, J. A. Geyer, and N. C. Waters. 2003. Oxindole-based compounds are selective inhibitors of Plasmodium falciparum cyclin dependent protein kinases. J. Med. Chem. 46:3877-3882.  

Waters, N. C. and J. A. Geyer. 2003. Cyclin-dependent protein kinases as therapeutic drug targets for antimalarial drug development. J. Expert. Opin. Therap. Targets. 7:7-17. 

Prigge, S. T., X. He, L. Gerena, N. C. Waters, and K. A. Reynolds. 2003. The initiating steps of a type II fatty acid synthase in Plasmodium falciparum are catalyzed by pfACP, pfMCAT, and pfKASIII. Biochemistry. 42:1160-9.

Waters, N. C., Wei, L., Li, Z.,  Kopydlowski, K. M., Woodard, C. L., and Prigge, S. T. 2002. Functional characterization of the acyl carrier protein (PfACP) and b-ketoacyl ACP synthase III (PfKASIII) from Plasmodium falciparum.  Mol. Biochem. Parasit. 123:85-94.
             
Li, Zhiyu, K. Le Roch , J. A. Geyer , C. L. Woodard , S. T. Prigge , J. Koh, C. Doerig , and N. C. Waters. 2001. Influence of human p16INK4 and p21CIP1 on the in vitro activity of recombinant Plasmodium falciparum cyclin dependent protein kinases. Biochem. Biophys. Res. Comm. 288:1207-1211.

15 October, 2008