Iain Cheeseman

Question

The kinetochore is a structure composed of more than 100 proteins that assembles at the centromere and is required for chromosome segregation and cell division. What is its role in the mechanisms that modulate and rewire core cell division processes across the cell cycle, within the different cells of an organism, and during evolution?

Approach

The goal of the Cheeseman Laboratory is to define the molecular mechanisms by which accurate cell division occurs. To grow from a single cell to the 30 trillion cells present in the human body, cells duplicate through cell division. During each cell division, the entire complement of genetic material must be accurately partitioned to the daughter cells. Even a single chromosome mis-segregation event can be catastrophic, resulting in the loss or gain of hundreds of genes, with severe consequences for development and disease.

The lab’s research focuses on the kinetochore, the central player in directing chromosome segregation. The kinetochore is a macromolecular structure composed of more than 100 different proteins that act to connect chromosomes to the microtubule polymers that power their movement, and integrate regulatory signals to ensure the proper timing and fidelity of chromosome segregation. Although the central importance of the kinetochore has long been appreciated, the molecular basis for its many activities remains poorly understood. We use parallel biochemical and cell biological approaches to analyze kinetochore composition, structure, organization, regulation, and how kinetochore proteins function to achieve proper chromosome segregation.

Using proteomics, biochemistry, cell biology, and functional approaches to examine this structure, Cheeseman has helped identify dozens of the kinetochore’s molecular components and their specific roles, and is defining how the attachments between kinetochores and spindle microtubules are regulated throughout cell division. His work is also shedding light on how the proteins that define the centromere are maintained over years or even decades. Because many cancers may be driven by errors in chromosome segregation, Cheeseman’s studies may inform cancer research. Certain cancer drugs target the connection between chromosomes and spindle microtubules, and some of the major proteins in the kinetochore complex have been implicated in leukemia and other diseases.

The Cheeseman lab is currently focused on how these core cell division processes are rewired across different physiological contexts. This includes between cell types, during development, depending on cell state, in disease, and across evolution.

Bio

Cheeseman completed his undergraduate training at Duke University, and his graduate work at the University of California, Berkeley, where he earned a doctorate in molecular and cell biology in 2002 in the lab of David Drubin and Georjana Barnes. He carried out his postdoctoral work in the lab of Arshad Desai at the Ludwig Institute for Cancer Research in San Diego and the University of California/San Diego. In 2007, he became a Member of Whitehead Institute and assistant professor at MIT.