We study the mechanisms that ensure stable genome inheritance during cell division. Every time a cell divides, it sends exactly one copy of each its chromosomes to the daughter cell. The process of chromosome segregation during cell division is of fundamental significance in cell and organismal biology. It is required for the proliferation of unicellular life and the development of multicellular organisms. It also shapes evolution. It is also important for our own well-being. Defective chromosome segregation plays a role many diseases including cancer. It is implicated in age-related infertility. Therefore, we want to define the mechanisms that achieve stable genome inheritance.

Achieving accurate chromosome segregation is extremely challenging. It necessitates the seamless integration of three complex systems: (1) a system dedicated to the generation of mechanical force, (2) a system that regulates force generation spatiotemporally, and (3) a mechanosensitive signaling cascade. We particularly focus on two of the three systems: the force generating kinetochore and the mechanosensitive signaling cascade also known as the Spindle Assembly Checkpoint (SAC). A distinguishing feature of our approach is that we study the interlinked systems quantitatively, as a whole, and in living human cells. This integrative approach provides insight into how the hundreds of proteins of the kinetochore and the SAC cooperate with one another to function, and reveals emergent mechanisms. The lab is currently engaged in two major endeavors.

Architecture-function analysis of the human kinetochore:
A distinguishing feature of mitosis is that it occurs at vastly different scales of space and time in different organisms. Eukaryotic cells can possess just three chromosomes (e.g. fission yeast), or three hundred (some butterflies and plants). These chromosome can be transported over a distance of less than 0.1 micron (check out the smallest eukaryote!) or over 10 microns (most vertebrates). Yet the eukaryotic kinetochore configures itself around a set of core, conserved proteins to drive accurate chromosome segregation. To understand how, we must define the spatial and dynamic organization of kinetochore proteins relative to one another and relative to the microtubule plus-end that they engage. With this goal in mind, we are developing cutting-edge FRET and super-resolution microscopy assays to define both nano-scale and sub micron-scale architecture of the human kinetochore. 
Aberrant SAC signaling, aneuploidy and Cancer Cell Biology:
We are also investigating the systems biology of SAC checkpoint. The SAC signaling cascade also contends with different cell sizes that can range from a few up to a few hundred cubic microns, even within the same organism during development. Similarly, the number of kinetochores can range from 3 to 300 (see above). How does the eukaryotic cell adapt the signaling cascade of the SAC to contend with these drastically divergent operating parameters? We will use a combination of in vivo measurements, molecular perturbations, and mathematical modeling to understand how the SAC is adapted during development, cancer cell proliferation, and aging.
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