Cancer Cell Biology
Area of interest
A critical link in mitosis, meiosis and cellular polarity involves the interaction between microtubule plus ends and localized protein domains. In the case of mitosis and meiosis the localized protein domain is a protein - DNA complex defined as the kinetochore. Microtubule interactions with chromosomes are required for proper chromosome segregation during anaphase. The cell contains a highly conserved, structural and regulatory mechanism to ensure high fidelity transmission of the genome to future progeny. However, compromised divisions can result in chromosome loss or aneuploidy, a precursor to the cancer onset. Furthermore, microtubules are the target of a large and diverse group of natural anticancer drugs. The success of anti-microtubule drugs in cancer therapy indicates that microtubules represent an excellent cancer target. Understanding how to target microtubules and microtubule based processes is essential for increasing drug specificity and activity. The goal of our work is to better understand how the kinetochore becomes established and, following attachment to dynamic microtubules, what is the nature of this attachment.
We have developed real-time imaging of yeast for purposes of quantitating the progression of mitosis, including spindle assembly/disassembly dynamics and chromosome movement in living cells. Our efforts allowed us to visualize the nucleus and mitotic spindle for the first time in live yeast and quantitate dynamic parameters throughout the cell cycle. We proceeded to extend these technologies to fluorescence microscopy and visualize individual proteins in live cells. Using a novel fluorescence speckle microscopy system we could map the site of tubulin assembly, and demonstrated that sites of force generation for nuclear and chromosomal movement localize to microtubule plus ends. Our live cell imaging technology coupled with the development of nucleic acid detection systems (lacO for DNA; MS2 bacteriophage for RNA), allow us to directly visualize nucleic acids in live cells. These are remarkable developments that cross boundaries into DNA repair, replication and recombination.
- 1978 - First demonstration that transcriptionally active genes are in a different chromatin structure than inactive genes. [Bloom K.S. and Anderson J.N. 1978. Cell 15: 141-150]
- 1982 - Demonstration that Yeast centromeres are organized in a unique and highly ordered chromatin structure [Bloom, K.S. and Carbon, J. 1982. Cell 29: 305-317]
- 1990 - The centromere has a nucleosome foundation. Four years later the centromere protein CENP-A was shown to contain a histone H3 like domain [Saunders, M.A., Grunstein, M. and Bloom, K.S. (1990). Molec Cell. Biology 10: 5721-5727]
- 1993 - First cloning of the microtubule-based motor, cytoplasmic dynein from yeast. Demonstration of nuclear migration defect pioneered the field of nuclear migration and spindle orientation. [Li, Y.-Y., Yeh, E., Hays, T., and Bloom, K. (1993). Proc. Natl. Acad. Sci. USA 90:10096-10100.]
- 1995 - Application of high resolution Video-Enhanced Differential Interference Microscopy to study yeast cell division. This paper provides evidence for a mitotic exit checkpoint. [Yeh, E., Skibbens, R., Cheng, J., Salmon, E.D., and Bloom, K. (1995) J. Cell Biol. 130:687-700]
Awards and Honors
- Career Development award from the National Institutes of Health (1987-1992)
- UNC's highest research award, the Ruth and Philip Hettleman Prize for Artistic and Scholarly Achievement (1989)
- Invited Instructor (1985-1990, 1995-1996) and Director (1997-1998) of the Physiology Course
- Symposium Speaker Annual Meeting of the American Society of Cell Biologists, Dec. 1984; Dec. 2002
- Co-Director of the Science Writers Fellowship Program at the Marine Biological Laboratory, Woods Hole, MA