Matthew Miller, Ph.D.

Research

The Miller lab will investigate the mechanisms that allow duplicated chromosomes to be accurately distributed when a cell divides. Cells in the human body will divide some 10,000 trillion times over an individual’s lifetime, and in each round of cell division, chromosomes must be accurately partitioned to the two daughter cells. A key player in this process is the kinetochore: This protein complex attaches chromosomes to the spindle that will pull them into the daughter cells—and actively monitors to ensure that the chromosomes remain attached correctly. Using an array of cutting-edge tools in biochemistry, biophysics, and gene editing, I will generate a comprehensive collection of mutants in which each individual residue in the proteins that make up the kinetochore, as well as those that comprise the spindle to which the kinetochore attaches, has been mutated, and my lab will determine which of these changes impairs chromosomal attachment and segregation. We will then reconstitute the activities of these protein machines in a test tube to discover the manner in which chromosome segregation fidelity has been disrupted. This work could lead to novel strategies for reducing the chromosomal segregation defects that give rise to many human diseases, including cancer and developmental disorders such as Down syndrome.