During mitosis, a full set of chromosomes must be equally transmitted to the offspring of each dividing cell. Failures in this process can result in numerous disorders, including birth defects and tumor progression. The Funabiki Lab studies how chromosomes signal in order to spatially and temporally orchestrate rapid assembly and disassembly of macromolecules that ensure accurate chromosome segregation.
Motivation of the Lab
We are composed of trillions of cells, which are all derived from a single egg cell. After fertilization, this one cell, containing 46 chromosomes (23 from your mother and 23 from your father), divides a number of times to make up a fully formed human being with trillions of cells. Even in adults, billions of cells are generated every day to replenish dying cells. Except for matured red blood cells, which lack a nucleus, and other specialized cells, most of those cells maintain the same original set of 46 chromosomes. Therefore, a number of mechanisms work to ensure that all replicated chromosomes are equally distributed to daughter cells every time a cell divides. However, in most cancer cells, the number and the composition of this chromosome set are drastically changed from the norm. Accumulating lines of evidence strongly suggest that the mechanism supporting proper chromosome segregation is compromised in those cancer cells, contributing to tumor development.
The Funabiki lab at the Rockefeller University in New York, NY pursues a wide range of questions, related to mitosis, genome integrity, and diseases connected to chromosome structure defects. We combine a variety of approaches, including Cryo-EM, state-of-art microscopy, proteomics and biochemistry.
Long-term goals of the Funabiki lab are:
To understand the molecular mechanisms and principles that ensure proper chromosome segregation during mitosis.
To understand the mechanisms that cause chromosome missegregation in cancer cells.
To understand how chromosome missegregation contributes to tumorigenesis.
To help design therapeutic approaches that selectively eliminate cancer cells without harming most normal cells.
Major Research Interests
Structure and Function
Chromosomes in interphase are relatively decondensed and support DNA replication and transcription during interphase. In contrast, mitotic chromosomes are ... read more
Kinetochores, Centromeres and Repetitive DNA
Human centromeres are composed of long arrays of repetitive sequences called alpha-satellite DNAs. There are diverse variations of centromere size and ... read more
Genome Integrity, Cancer and Innate Immunity
Many cancer cells exhibit a “chromosome instability (CIN)” phenotype, where chromosomes frequently fail to equally distribute to daughter cells. How ... read more