Anna Mapp, CHEMIST, Ann Arbor, Michigan
"Every human disease could be addressed by transcription-targeted therapeutics."
What She's Doing
Anna Mapp's laboratory has two major goals: to understand interactions between proteins that happen naturally in a cell, and to promote normal interactions while blocking problematic ones.
For aspiring scientists, Mapp's best advice is to "find what you love." What she loves is chemical biology—using chemical tools and techniques to understand complex biological systems.
University of Michigan, Ann Arbor
The Once and Future King by T.H. White
Fly fishing—"I take my six year-old son a lot. He caught his first fish by himself this summer."
FAVORITE SUBJECT IN HIGH SCHOOL
As an undergraduate student, Mapp had no idea that she would become a chemist. With plans to major in East Asian Studies, Mapp says that it was only when she was inspired by her organic chemistry professor that she decided on a science career.
"After watching my professor apply a simple reaction to a more complex system, I was hooked."
Today, Mapp applies her work in organic chemistry to the process of transcription—a cell's method of copying information from genes into messenger RNA, which acts as a blueprint for making proteins. Errors in transcription are linked to diseases like diabetes and cancer, but scientists know very little about the molecular interactions happening behind the scenes.
To learn more about how errors occur during transcription and how to prevent them from happening, Mapp and her colleagues use organic molecules as "probes." The small molecules act as stand-ins for proteins that attach to others when errors occur in the transcription process. If Mapp can figure out how these proteins interact with one another, she can develop drugs to block harmful bonds while encouraging normal ones.
"In transcription, the traditional techniques don't work that well for telling you that Protein A is directly interacting with Protein B, and that's what you need to know if you really want to discover drugs that target those interactions."
One set of interactions Mapp has worked to block are those that lead to the production of the ErbB2 growth receptor. In excess, that protein signals cells to grow and divide without regulation, which can contribute to the growth of tumors. Mapp has identified small molecules that interrupt the process of ErbB2 production.
By themselves, those molecules aren't always effective because they tend to form weak complexes-or linked groups—with transcriptional proteins. Mapp hypothesized that if she used agents that blocked other parts of ErbB2 function in tandem with a transcription blocker she identified, she might more effectively stop ErbB2 from being expressed and help prevent tumor growth.
She found that two molecules could each reduce the transcription of ErbB2 by about 30 percent by themselves. However, when applied together, they decreased transcription by 85 percent. That gain in effectiveness is known as a synergistic increase, in which the combined effect of two agents is greater than the sum of its parts. Recent studies in an animal model of head and neck cancer suggest that this combination strategy may keep tumors from growing in living organisms.
Not only do Mapp's findings provide a framework for possible cancer therapies, but they provide an example of transcriptional blockers as an effective tool for scientists seeking to solve diverse biomedical problems.