Chemical genetics of Plasmodium falciparum.

Malaria caused by Plasmodium falciparum is a disease that is responsible for 880,000 deaths per year worldwide. Vaccine development has proved difficult and resistance has emerged for most antimalarial drugs. To discover new antimalarial chemotypes, we have used a phenotypic forward chemical genetic approach to assay 309,474 chemicals.

Circumventing anti-androgen resistance by molecular design.

Nuclear/steroid hormone receptors (NHRs) function as ligand-dependent transcriptional regulators of diverse sets of genes involved in development and homeostasis. Mutations to the androgen receptor (AR), a member of NHRs, have been linked to the failure of hormonal therapy in the treatment of prostate cancer (PCa). It has been proposed that AR mutations such as Thr877 → Ala, Trp741 → Leu and Trp741 → Cys that cause anti-androgens such as flutamide and bicalutamide to function as agonists are likely associated with anti-androgen withdrawal syndrome in PCa therapy.