A thorough knowledge of the regulators in pathways controlling cellular reproduction, differentiation and migration is essential to understand the processes that go awry in neoplastic disease, and provides the basis for the development of novel therapeutic interventions. We focus our studies on the novel ‘G’ family (cyclins G1, G2 and I (G3)) of atypical cyclins. Cyclins G1 and G2, unlike classical cyclins, are not associated with cell cycle progression, rather they are growth inhibitory. They are weakly expressed in normal replicating cells but upregulated in response to diverse growth inhibitory stimuli coincident with the onset of cell cycle arrest. We have shown that cyclin G2, like cyclin G1, associates with active protein Phosphatase 2A. Interestingly, ectopic expression of either leads to a G1/S-phase cell cycle arrest. Both cyclins G1 and G2 are evolutionarily conserved from fish to humans, suggesting an ancient and important cellular function. Recent microarray analyses from a variety of studies have strongly implicated this unique cyclin family as negative coordinators of the cell cycle and promoters of cellular differentiation.

My lab uses a combination of cell and molecular biology and protein biochemistry to study the role of cyclin G family members in the regulation of cellular proliferation and differentiation in various model systems. These studies encompass several projects relevant to the fields of immunology, developmental neuroscience and cancer cell biology. We have recently identified several novel cyclin G family interactions and are seeking to:

i) Characterize endogenous cyclin G2, G1 and I protein complexes in native tissues.

ii) Determine the polypeptide regions required for their interaction with identified binding partners.

iii) Determine the relevance of these cyclin interactions to their functions in physiological settings.

Specifically we are interested in the function and mechanisms of action of Cyclin G1 and G2 regulated complexes in:

1) Responses to B cell receptor signaling and tolerance induction in developing lymphocytes:

2) p53 tumor-suppressor pathway signaling:

3) Cell cycle arrest and differentiation of neurons in the developing cerebellum:

4) Cellular responses to environmental stress signals (hypoxia and oxidative stress):

5) Regulation of centrosomes and microtubules during cell division.