At the National Center for Natural Products Research, we have isolated several novel natural products that have potent activit

Ameeta K. Agarwal

Education

1995 Ph.D., Biology, University of Maryland, Baltimore, Maryland

1987 M.S., Microbiology, University of Bombay, Bombay, India

1985 B.S., Microbiology, University of Bombay, Bombay, India

Research Experience

2009-present Research Associate Professor, Department of Pharmacology, University of Mississippi, University, MS

2008-present Senior Scientist, National Center for Natural Products Research, University of Mississippi, University, MS

2002-2008 Research Scientist, National Center for Natural Products Research, University of Mississippi, University, MS

Focus of research: Genomic, molecular and genetic approaches for identifying the mechanism of action of novel antifungal compounds.

1998-2001 Plant Molecular Biologist, Monsanto Company, St. Louis, MO

1995-1998 Postdoctoral Research Associate, Monsanto Company, St. Louis, MO

Focus of research: Genetic engineering of metabolic pathways in crop plants.

1988-1994 Ph.D., Biology, University of Maryland, Baltimore, MD

Focus of research: Developmental regulation of gene expression in the cellular slime mold, Dictyostelium discoideum.

Ongoing Research

At the National Center for Natural Products Research, we have isolated several novel natural products that have potent activity against opportunistic fungal pathogens, including Candida albicans, C. krusei, Cryptococcus neoformans, and Aspergillus fumigatus. We have also identified natural products that can enhance the activity of fluconazole in resistant strains of Saccharomyces cerevisiae that over-express C. albicans efflux pumps, as well as in clinical isolates of C. albicans that are resistant to fluconazole. My research is focused on identifying the mechanism of action of these novel compounds using S. cerevisiae as a model organism. We are using genomic profiling approaches (e.g., DNA microarrays) for these studies, and the molecular targets identified are being validated using genetic and molecular strategies (e.g., use of deletion mutants, multicopy library screening for resistance, etc.). The overall goal of this project is to identify new compounds as well as new pathways for the development of new treatments for the major AIDS- and cancer-related disseminated fungal infections.

We are also conducting mechanistic studies in the major fungal pathogen C. albicans. This work will not only serve as a starting point towards the development of novel antifungal therapies, but it will also broaden our understanding of the basic biology of fungal pathogens, with potential clues for pathogenesis, virulence, and resistance mechanisms.

Funded Research Projects

“New Drugs for Opportunistic Infectious Diseases” NIH/NIAID, 2R0AI27094-20A1, 07/01/09 - 06/30/14, PI: Alice M. Clark; Co-PI: Ameeta K. Agarwal

“Molecular Targets of Novel Antifungal Compounds” NIH/NIAID, 5R21AI067873-02, 9/20/07 - 2/28/10, PI: Ameeta K. Agarwal, Co-PI: Michael C. Lorenz (University of Texas Health Science Center at Houston)

Publications

Zhang, X., Jacob, M. R., Ranga Rao, R., Wang, Y-H, Agarwal, A. K., Newman, D. J., Khan, I. A., Clark, A. M., and X. C. Li (2012) Antifungal cyclic peptides from the marine sponge Microscleroderma herdmani. Res. Rep. Med. Chem. 2:7-14.

Xu, T. X., Tripathi, S. K., Feng, Q., Lorenz, M. C., Wright, M. A., Jacob, M. R., Mask, M. M., Baerson, S. R., Li, X. C., Clark, A. M., and A. K. Agarwal (2012) A potent plant-derived antifungal acetylenic acid mediates its activity by interfering with fatty acid homeostasis. Antimicrob. Agents Chemother. 56:2894-2907.

Agarwal, A., Tripathi, S., Xu, T., Jacob, M., Li, X. C., and A. Clark (2012) Exploring the molecular basis of antifungal synergies using genome-wide approaches. Front. Microbiol. 3:115.

Huang, Z., Chen, K., Xu, T., Zhang, J., Li, Y., Li, W., Agarwal, A. K., Clark, A. M., Phillips, J. D., and X. Pan (2011) Sampangine inhibits heme biosynthesis in both yeast and human. Eukaroyt. Cell. 10:1536-1544.

Li, X. C., Babu, K. S., Jacob, M. R., Khan, S. I., Agarwal, A. K., and A. M. Clark (2011) Natural product-based 6-hydroxy-2,3,4,6-tetrahydropyrrolo[1,2-a]pyrimidinium scaffold as a new antifungal template. ACS Med. Chem. Lett. 2:391-395.

Xu, T., Feng, Q., Jacob, M. R., Avula, B., Mask, M. M., Baerson, S. R., Tripathi, S. K., Mohammed, R., Hamann, M. T., Khan, I. A., Walker, L. A., Clark, A. M., and A. K. Agarwal (2011) The marine-derived polyketide endoperoxide plakortide F acid mediates its antifungal activity by interfering with calcium homeostasis. Antimicrob. Agents Chemother. 55:1611-1621.

Xu, W. H., Jacob, M. R., Agarwal, A. K., Clark, A. M., Liang, Z. S., and X. C. Li (2010) ent-Kaurane glycosides from Tricalysia okelensis. Chem. Pharm. Bull. (Tokyo) 58:261-264.

Xu, W. H., Ding, Y., Jacob, M. R., Agarwal, A. K., Clark, A. M., Ferreira, D., Liang, Z. S., and X. C. Li (2009) Puupehanol, a sesquiterpene-dihydroquinone derivative from the marine sponge Hyrtios sp. Bioorg. Med. Chem. Lett. 19:6140-6143.

Xu, W. H., Jacob, M. R., Agarwal, A. K., Clark, A. M., Liang, Z. S., and X. C. Li (2009) Flavonol glycosides from the native American plant Gaura longiflora. Heterocycles 78:2541-2548.

Xu, W. H., Jacob, M. R., Agarwal, A. K., Clark, A. M., Liang, Z. S., and X. C. Li (2009) Verbesinosides A-F, 15, 27-cyclooleanane saponins from the American native plant Verbesina virginica. J. Nat. Prod. 72:1022-1027.

Li, X. C., Jacob, M. R., Khan, S. I., Ashfaq, K. M., Babu, K. S., Agarwal, A. K., Elsohly, H. N., Manly, S. P., and A. M. Clark (2008) Potent in vitro antifungal activity of naturally occurring acetylenic acids. Antimicrob. Agents Chemother. 52:2442-2448.

Agarwal, A. K., Xu, T., Jacob, M. R., Feng, Q., Li, X. C., Walker, L. A., and A. M. Clark (2008) Genomic and genetic approaches for the identification of antifungal drug targets. Infect. Disord. – Drug Targets. 8:2-15.

Pan, Z., Agarwal, A. K., Xu, T., Feng, Q., Baerson, S. R., Duke, S. O., and A. M. Rimando (2008) Identification of molecular pathways affected by pterostilbene, a natural dimethylether analog of resveratrol. BMC Med. Genomics. 1:7.

Agarwal, A. K., Xu, T., Jacob, M. R., Feng, Q., Lorenz, M. C., Walker, L. A., and A. M. Clark (2008) Role of heme in the antifungal activity of the azaoxoaporphine alkaloid sampangine. Eukaryot. Cell. 7:387-400.

Singh, K., Agarwal, A. K., Khan, S., Walker, L. A., and B. L. Tekwani (2007) Growth, drug susceptibility and gene expression profiling of Plasmodium falciparum cultured in medium supplemented with human serum or lipid-rich bovine serum albumin. J. Biomol. Screen. 12:1109-1114.

Li, X-C., Jacob, M. R., Ding, Y., Agarwal, A. K., Smillie, T. J., Khan, S. I., Nagle, D. G., Ferreira, D., and A. M. Clark (2006) Capisterones A and B, which enhance fluconazole activity in Saccharomyces cerevisiae, from the marine green alga Penicillus capitatus. J. Nat. Prod. 69:542-546.

Baerson, S. R., , Sánchez-Moreiras, A., Pedrol-Bonjoch, N., Schulz, M., Kagan, I. A., Agarwal, A. K., Reigosa, M. J., and S. O. Duke (2005) Detoxification and transcriptome response in Arabidopsis seedlings exposed to the allelochemical benzoxazolin-2(3H)-one (BOA). J. Biol. Chem. 280: 21867-21881.

Hossain, C. F., Kim, Y-P., Baerson, S. R., Zhang, L., Bruick, R. K., Mohammed, K. A., Agarwal, A. K., Nagle, D. G., and Y-D. Zhou (2005) Saururus cernuus lignans - potent small molecule inhibitors of hypoxia-inducible factor-1. Biochem. Biophys. Res. Commun. 333: 1026-1033.

Zhou, Y-D., Kim, Y-P., Li, X-C., Baerson, S. R., Agarwal, A. K., Hodges, T. W., Ferreira, D., and D. G. Nagle (2004) Hypoxia-inducible factor-1 activation by (-)-epicatechin gallate: Potential adverse effects of cancer chemoprevention with high-dose green tea extracts. J. Nat. Prod. 67: 2063-2069.

Agarwal, A. K., Rogers, P. D., Jacob, M. R., Barker, K. S., Cleary, J. D., Walker, L. A., Nagle, D. G., and A. M. Clark (2003) Genome-wide expression profiling of the response to polyene, pyrimidine, azole, and echinocandin antifungal agents in Saccharomyces cerevisiae. J. Biol. Chem. 278: 34998-35015.

Duke, S.O., Dayan, F. E., Baerson, S. R., Romagni, J.G., Agarwal, A. K., and A. Oliva. (2003) Natural phytotoxins with potential for development in weed management strategies. In Chemistry of Crop Protection, G. Ramos and G. Voss, eds., Wiley-VCH Verlag, Weinheim, Germany, pp. 143-154.

Agarwal, A. K., Qi, Y., Woerner, M., Bhat, D. G., and S. M. Brown (2001) Gene isolation and characterization of two acyl CoA oxidases from soybean with broad substrate specificities and enhanced expression in the growing seedling axis. Plant Molecular Biology. 47: 519-531.

Agarwal, A.K., Parish, S. N., and D. D. Blumberg (1999) Cell type specific shut off of ribosomal protein gene expression during development of Dictyostelium discoideum. Differentiation. 65: 73-88. Journal cover photo is from this paper.

Agarwal, A.K. and D. D.Blumberg (1999) Dictyostelium ribosomal protein genes and the elongation factor 1B gene show coordinate developmental regulation which is under post-transcriptional control. Differentiation. 64: 247-254.

Agarwal, A. K., Sloger, M. S., Oyama, M., and D. D. Blumberg (1994) Analysis of a novel cAMP-inducible prespore gene in Dictyostelium discoideum: Evidence for different patterns of cAMP regulation. Differentiation. 57: 151-162.

Blumberg, D. D., Agarwal, A. K., Sloger, M. S., and B. K. Yoder (1990) Gene expression and chromatin structure in the cellular slime mold, Dictyostelium discoideum. Developmental Genetics. 12: 65-77.

Patents

Adams, T., Agarwal, A. K., Ahrens, J., Ball, J. A., Basra, A., Bell, E., Bradshaw, T. L., Chomet, P. S., Crowley, J. H., Deikman, J., Deng, M., Donnarummo, M., Duff, K. F. Z., Duff, S., Edgerton, M. et al. (2009) Transgenic plants with enhanced agronomic traits. Patent No. US-20090100536.

Banu, G., Bell, E., Boddupalli, R., Kretzmer, K. A., Daly, M., Deikman, J., Deng, M., Dong, J., Chomet, P. S., Edgerton, M. D., Adams, T. H., Ruff, T. G., Agarwal, A. K., Ahrens, J., Ball, J., A. et al. (2004) Transgenic maize with enhanced phenotype. Patent No. WO 2004053055.

Agarwal, A. K., Liu, J-D. and D. Lahiri (2003) Plant sequences associated with the beta-oxidation metabolic pathway. Patent No. US-6518488.

Agarwal, A. K., Brown, S. M. and Y. Qi (1997) Method for controlling seed germination using soybean acyl-CoA oxidase sequences. Patent No. WO-9744465.

Professional Memberships

American Association for the Advancement of Science

American Society for Biochemistry and Molecular Biology

American Society for Microbiology

Genetics Society of America