University of Vermont Cancer Center Member Profile

Jason Stumpff, PhD
Program Co-Leader, Cancer Host and Environment, UVM Cancer Center
Professor, Molecular Physiology and Biophysics
Full Member
Cancer Host and Environment (CHE)
Academic Interests
The long-term goal of my lab is to understand the mechanisms that move and organize chromosomes during cell division and determine how mitotic errors arise and contribute to the initiation and progression of cancer. We specifically focus on determining how kinesin motor proteins and mitotic spindle microtubules promote accurate chromosome segregation during mitosis from the single molecule to whole organism scales. All kinesin superfamily members share sequence homology within their catalytic “motor” domains, however, there is significant diversity among the motility, microtubule affinity, force generation, and oligomerization properties of the 45 kinesin proteins encoded by the human genome. Precisely how this variation in kinesin activity is achieved remains an open question. Furthermore, there are significant conceptual gaps in our understanding of how kinesin activities are spatially and temporally regulated in cells and how alterations in their function contribute to tumorigenesis. We are approaching these fundamental questions related to mitotic kinesin function across biological scales utilizing a combination of quantitative cell biology and in vitro biophysical approaches. This work led to the recent discovery that KIF18A is specifically required for growth of chromosomally unstable tumor cells and the identification of KIF18A as a promising therapeutic target
The long-term goal of my lab is to understand the mechanisms that move and organize chromosomes during cell division and determine how mitotic errors arise and contribute to the initiation and progression of cancer. We specifically focus on determining how kinesin motor proteins and mitotic spindle microtubules promote accurate chromosome segregation during mitosis from the single molecule to whole organism scales. All kinesin superfamily members share sequence homology within their catalytic “motor” domains, however, there is significant diversity among the motility, microtubule affinity, force generation, and oligomerization properties of the 45 kinesin proteins encoded by the human genome. Precisely how this variation in kinesin activity is achieved remains an open question. Furthermore, there are significant conceptual gaps in our understanding of how kinesin activities are spatially and temporally regulated in cells and how alterations in their function contribute to tumorigenesis. We are approaching these fundamental questions related to mitotic kinesin function across biological scales utilizing a combination of quantitative cell biology and in vitro biophysical approaches. This work led to the recent discovery that KIF18A is specifically required for growth of chromosomally unstable tumor cells and the identification of KIF18A as a promising therapeutic target