Cell cycle plasticity in human health and disease
Cell cycle plasticity
How does the cell cycle adapt to different biological or diseased contexts?
What mechanistic paths can cells take through the cell cycle in response to changes in their internal state or environment?
Cell cycle mapping
We combine hyperplexed, single cell imaging with manifold learning to map the paths that cells take through the cell cycle
What are we interested in?
Studying the cell cycle in its native environment
Through decades of biochemical and genetic studies mostly in yeast and immortalized mammalian cell cultures, we have assembled an extensive model of the cell cycle and how it is regulated. However, we now know that cells do not always traverse the same mechanistic paths en route to cell division. To explore this plasticity in cell cycle regulation, we are mapping the cell cycles of various cell types embedded in their native, 3-dimensional tissue environment.
Role of the tumor microenvironment in cancer cell proliferation
The tumor microenvironment (TME) plays a major role in the initiation, progression and drug sensitivity of tumors. However, we know very little about how the TME influences cancer cell proliferation and arrest. Does the TME expand or limit the repertoire of cell cycle paths available to a tumor cell? Using tissue specimens of patient tumors, we are trying to understand how the TME influences the proliferation/arrest decision of cancer cells.
Precision medicine to target tumor-specific cell cycles
Cancer is a disease characterized by uncontrolled cell proliferation and many of the mutations that drive tumorigenesis occur directly in the proteins that control the cell cycle. Using patient-derived organoids, we are mapping the cell cycles of individual tumors to identify specific vulnerabilities in the cancer cell cycle and targeting them with personalized therapy.