Pradipsinh K. Rathod

Professor of Chemistry
(Malaria Pharmacology, Functional Genomics
Ph.D., Oregon Health Sciences University, 1982)

(206) 616-5179
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.

However, rational drug development remains an inexact science. The success and failure of drugs is often attributed to interesting chemical rationalizations but, individually, such explanations have had disappointing predictive value in pharmacology.

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. The value and power of chemical biology is best appreciated in the context of understanding and curing diseases.

Four Areas of Interest

1. Cellular control mechanisms influence drug selectivity. The Rathod lab discovered that some malarial drug targets may be uniquely sensitive to inhibitors in part due to tight protein-nucleic acid interactions. Such autoregulation in malaria is different from what is seen in the host. Such insights have also allowed for improved strategies for expressing malaria proteins in functional form.
2. Drug resistance in malaria emerges from parasite populations with mutator-like phenotypes. The Rathod lab is developing a more detailed model for this phenotype and identifying the molecular players involved in the process.
3. High-value drug targets are attacked in multiple ways. Pyrimidine biosynthesis in malaria can be targeted with high selectivity by starting with appropriate pro-drugs, by supplementing non-selective antifolates with rescuing nutrients that only the host can use, and by disrupting unique protein-protein interactions.
• The Rathod lab targets malarial thymidylate synthase
• Wwith M. Phillips (U of Texas, SW Med Center), we also target malarial dihydroorotate dehydrogenase.
4. New tools for malaria.
• The Rathod lab, J. DeRisi (UCSF) and P. Brown (Stanford), developed the first microarrays for malaria. Current efforts are directed at applications to improve our understanding of malaria gene regulation, particularly in the context of drug action. 
• QTL mapping techniques are used to dissect drug resistance traits and gene expression, with support from T. Wellems (NIH) and M. Ferdig (U. Notre Dame).
• Microfluidic approaches are used to model critical aspects of malaria pathobiology, with the aim of understanding variations in disease outcome.
• Cell-free protein expression strategies have opened up possibilities for genome-wide malarial protein expression in functional form.