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Pradipsinh K. Rathod

Pradipsinh K. Rathod, PhD. Professor of Chemistry
Ph.D. Oregon Health Sciences University, 1982

(Malaria Pharmacology, Functional Genomics)

(206) 221-6069
or (206) 616-5179

Email: rathod@chem.washington.edu

Research Interests

Malaria Pharmacology

Malaria is a major cause of morbidity and mortality in the world, with about 2 million deaths and over 500 million infections per year. With the emergence of resistance against traditional drugs, there is an urgent need for new, affordable medicines against Plasmodium. Faithful, disciplined application of chemical principles to increasingly sophisticated understanding of biology can lead to new drug targets, candidate drugs, and can help reveal new principles in biology.

Four Areas of Interest

  1. TARGETING HIGH-VALUE PYRIMIDINE BIOSYNTHESIS ENZYMES with selectivity by starting with host-parasite protein differences at the active-site, by appropriate pro-drugs, by supplementing non-selective antifolates with rescuing nutrients that only the host can use, or by disrupting unique protein-protein interactions. The Rathod lab targets malarial:  

    • Thymidylate synthase.
    • Dihydroorotate dehydrogenase, with M. Phillips (Texas, SW Med Center)

  2. MUTATOR-LIKE PHENOTYPES WHICH DRIVE ACQUISITION OF DRUG RESISTANCE IN MALARIA PARASITES. The Rathod lab now has a detailed model for this phenotype and has identifying genomic loci involved in the process.

  3. DRUG SELECTIVITY THROUGH SYSTEM-WIDE HOST-PARASITE DIFFERENCES IN GENE REGULATION. The Rathod group discovered that some malarial drug targets may be uniquely sensitive to inhibitors in part due to tight parasite-specific protein-nucleic acid interactions. Such insights have also allowed for improved strategies for expressing malaria proteins in functional form

  4. NEW TOOLS FOR MALARIA RESEARCH.
    • DNA microarrays are used to understand malaria gene regulation, particularly in the context of drug action.
    • QTL mapping helps dissect resistance traits and control of gene expression
    • Microfluidics help model malaria pathobiology.
    • Cell-free protein expression allows access to functional malarial proteins

Representative Publications

Deng X, Gujjar R, El Mazouni F, Kaminsky W, Malmquist NA, Goldsmith EJ, Rathod PK, Phillips MA. Structural plasticity of malaria dihydroorotate dehydrogenase allows selective binding of diverse chemical scaffolds.   J Biol Chem. 2009 Jul 28. [Epub ahead of print] PMID: 19640844

Herricks T, Antia M, and Rathod PK. 2009 “Deformability limits of Plasmodium falciparum-infected red blood cells”, Cell Microbiol. 2009 Apr 30. [Epub ahead of print]  PMID: 19438513

Gujjar, R., Marwaha, A., El Mazouni, F., White, J., White, K. L., Creason, S.,  Shackleford, D. M., Baldwin, J., Charman, W. N., Buckner, F.S., Charman, S., Rathod, P.K. and Phillips, M.A. 2009. “Identification of a metabolically stable triazolopyrimidine-based dihydroorotate dehydrogenase inhibitor with anti-malarial activity in mice”, J. Med. Chem. 52 (7), 1864-1872 PMID: 19296651

More Publications ...

Awards & Activities

Grand Challenges Explorations Award, B&MG Foundation

Co-Chair, Molecular Parasitology Meeting, Woods Hole, MA

Co-Chair, Keystone Meeting, Parasite Drug Development

More Awards and Activities