Investigators and Program Directors

Research Interests

We use laser microsurgery and sophisticated imaging techniques (light- and electron microscopy) to study functions of the centrosome in vertebrates. In contrast to genetic knock-outs, laser microsurgery allows one to destroy the centrosome as an organelle without eliminating those individual centrosomal components, essential for cell viability, from the cytoplasmic pool. This approach has revealed that cells lacking centrosomes contain normal amounts of microtubules, enter mitosis and form a functional mitotic spindle, ultimately producing acentrosomal daughter cells. Surprisingly, however, the acentrosomal daughter cells become arrested during the ensuing G1 and never initiate DNA synthesis. These results demonstrate that the essential function of the centrosome in vertebrates is not to organize microtubules, as was believed for more than a 100 years. Instead, centrosomes are somehow involved in regulating cell cycle progression. Importantly, the centrosome does not regenerate in the G1-arrested cells. However, when centrosomes are destroyed in cells arrested in S phase, new centrosomes form by de novo assembly. This de novo pathway leads to formation of random numbers of centrioles (2-14 per cell). The de novo assembly of centrioles is somehow inhibited in the presence of just a single pre-existing centriole since it occurs only when all of the original centrioles are destroyed. Together these data reveal that cells possess a mechanism that monitors the presence of a centrosome in the cell, it's disappearance of the centrosome leads to either a block in cell cycle progression or to the formation of multiple new centrioles. Since redundant centrosomes are often associated with malignant tumors, the latter mechanism is potentially relevant for cancerous transformation.

We also studying mechanisms of mitotic spindle formation in vertebrates in the presence of centrosomes and when these organelles are absent.

Contact Information

Phone: (518) 486-5339
Fax: (518) 486-4901
E-mail: khodj@wadsworth.org.