Biophysics, Cell Biology
The University of Texas Southwestern Medical Center
Dr. Rosen is also professor and chair of the Department of Biophysics at the University of Texas Southwestern Medical Center, where he holds the Mar Nell and F. Andrew Bell Distinguished Chair.
Molecular Mechanisms of Cell Organization on Micron Length Scales
Just as steel girders support modern skyscrapers, actin filaments give cells their shape and strength. But actin has many other roles: it drives cells to migrate and change shape, and its regulation is crucial in preventing cancer, tumor metastasis, and immunodeficiency disorders.
When Michael Rosen started his lab at the Memorial Sloan Kettering Cancer Center, in 1996, he wanted to learn how signals from outside the cell regulate the actin cytoskeleton. A chemist by training, he studied the physical basis of that information flow by examining the three-dimensional arrangements of atoms in individual actin molecules and how the atoms interact with their binding partners. Rosen’s broad technical expertise and ability to complement his structural studies with an array of biophysical and biochemical techniques quickly brought him to the forefront of the field.
In 2002, Rosen moved his lab to the University of Texas Southwestern Medical Center. There, he continued to study actin, looking at how individual actin filaments are formed and destroyed in response to upstream signaling networks, and how molecules in these pathways fluctuate on picosecond to millisecond timescales in order to receive and transmit information, often through allosteric changes.
More recently, Rosen’s team has focused on what happens structurally and functionally when thousands to millions of individual molecules assemble to create micron-scale structures that are involved in gene regulation, signal transduction, and RNA metabolism. Many of these structures constantly rearrange and exchange their constituent parts with the surrounding medium. As a result, it’s much less clear how their physical properties relate to their molecular features, and how those physical properties define biochemical and biological functions that can be regulated in vivo.
Because some of these micron-scale structures go awry in neurodegenerative diseases and cancer, Rosen hopes that by deciphering their normal biology, he can better understand the diseases, and ultimately suggest new treatments.