Grants - Massachusetts - Designated Grants - 2014

Mo Motamedi, Ph.D.

Almost all cells of an individual share the same genetic information. Yet each individual has many different cell types with distinct characteristics and functions (e.g. skin cells and brain cells of the same individual are indistinguishable genetically). One the most vexing questions in biology is: how is this dizzying array of cell types made within an individual, all of which come from the same blueprint of genetic information?  
 
We now know what differs among the different cell types of an individual is not the genetic information; instead, it is the ‘on’ and ‘off’ state of genes in that cell type. In other words, a cell’s unique gene expression signature determines its characteristics. A molecular memory system, called epigenetics, establishes and remembers the cell type’s unique gene expression pattern during development. 
 
One way by which cells become cancerous is by losing their ability to remember who they are. This also impairs their ability to protect their DNA against damage and instability. Recent work has revealed the identity of some proteins whose job is to regulate these important processes. We have found that two of these proteins work together to create a special DNA structure, which protects our DNA against instability and remembers if a gene is ‘on’ or ‘off’. We plan to understand the mechanism by which these and other proteins regulate gene expression and genome stability. This work impacts our basic understanding of many different cancers, and will likely allow the development of new drugs and new strategies for killing or reprogramming cancer cells.