Iain Cheeseman

Question

What is the molecular machinery that helps to direct core cellular processes? How are these processes and their underlying machinery modulated and rewired across different contexts such as between cell types, during development, depending on cell state, in disease, and across evolution?

Approach

The Cheeseman laboratory is passionate about understanding the molecular basis for core cellular processes with a focus on cell division and how the chromosomes are divided evenly during the process, called chromosome segregation. Much of our work has focused on the kinetochore, the central player in directing chromosome segregation. The kinetochore is a complex structure composed of more than 100 different proteins that act to connect chromosomes to the cellular system that powers their movement, and integrate regulatory signals to ensure the proper timing and fidelity of chromosome segregation. Our work helped drive a transformation towards viewing the kinetochore as a molecular machine. We discovered numerous kinetochore components and have been instrumental in combining these individual pieces to generate an integrated molecular model for kinetochore function. To achieve this, our laboratory has used a variety of approaches in cultured human cells and other experimental systems. We have also conducted large-scale cell biological studies, including the use of optical pooled screening to analyze single-cell traits and shape across millions of cells.

In our current work, we are building on this molecular framework to understand how core cellular processes and their underlying molecular machines are rewired across different contexts. This includes between cell types, during development, depending on cell state, in disease, and across evolution. Cells can adapt to meet the requirements of different situations, but how their alternative programs are orchestrated remains poorly understood. We are working to understand how different cellular processes are rewired and it has forced us to reconsider our assumptions about how key molecular players are controlled and modulated to achieve these different programs. This includes exploring how these players are altered at the transcriptional, translational, and post-translational levels, as well as identifying previously-hidden functional protein isoforms or variants of known proteins.

Our recent work has identified thousands of protein variants, including a key cell division component, and shown how their production is regulated across the cell cycle. We have shown that these variants, and regulation of when they are made, is important for proper cell division. This work could be relevant for improving certain chemotherapies. In addition, we are currently exploring the relevance of various protein variants to health and disease.

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. He became a full professor at MIT in 2018, was named as the Herman and Margaret Sokol Professor of Whitehead in 2020, and became associate department head for MIT Biology in 2022. In addition to his research, Cheeseman is dedicated to enabling effective training and increasing diversity in the next generation of scientists, including their ability to thrive in a range of careers. He is a member of MIT Biology’s Diversity and Inclusion Committee and ASCB’s Women in Cell Biology Committee, and a Board Member and Treasurer for ASAPbio – a non-profit organization working to promote innovations in life science communication.