Research

We have discovered that inhibiting proteins that 'read' the histone code in bloodstream trypanosomes perturbs movement and causes the parasites to acquire characteristics ordinarily seen only in the insect stage of the life cycle. Because the insect environment is so different from the mammalian bloodstream, insect-stage cells are very poorly adapted to living in mammalian hosts. We are interested in screening small-molecule inhibitors to see whether they bind to trypanosome bromodomains. If these inhibitors could be identified, the resulting reprogramming of bloodstream trypanosomes to insect-stage cells would make the parasites vulnerable to the mammalian immune system, ideally leading to new therapeutic strategies to treat trypanosomiasis. We are also working toward characterizing the molecular mechanisms by which bromodomain inhibition results in transcriptional reprogramming.