Cyclin D1 is best known as the regulatory subunit of a dimericholoenzyme including the cell cycle-dependent kinase CDK4, which phosphorylates and inactivates the retinoblastoma protein Rb to promote progression through the G1-S phase of the cell cycle. The role of cyclin D1 in processes outside of its well-known function in cell cycle is relatively under-explored. My previous studies in Dr. Richard G. Pestell’s lab reveal that cyclin D1 acts to promote cellular migration by inhibiting Rho/ROCK signaling and expression of thrombospondin-1 (TSP-1), an extracellular matrix protein that regulates cell migration in many settings including cancer (Molecular and Cellular Biology.2006; 26(11): 4240-56). It has been shown that p27^KIP1 has a pro-migratory function through inhibiting RhoA activity. Cyclin D1 promotes cellular migration via up-regulating p27^KIP1 abundance and physical interaction with p27^KIP1 (Cancer Research.2006; 66(20): 9986-94). Alternate cyclin D1 mRNA splicing modulates p27^KIP1 binding and cell migration (Journal of Biological Chemistry 2008; 283(11): 7007-15). DNA damage can initiate cancer. Radiological and chemical agents used to treat cancer patients often cause DNA damage. My studies suggest that alternative cyclin D1 splice forms differentially regulate the DNA damage response (Cancer Research. 2010; 70(21): 8802-11).

The DACH1 gene encodes a protein that inhibits cellular proliferation, contact-independent growth and breast tumor metastasis. But prior publications about Dach1 function were mostly from in vitro and overexpression studies. The role of endogenous Dach1 in tumorigenesis in vivo still needs to be addressed.

 Current Research Projects

• The role of cyclin D1 in DNA repairs.
• The role of cyclin D1 in DNA methylation.
• The role of Dach1 in tumotigenesis in vivo.

 Future Plans
To examine the roles of cyclin D1 in chromatin modulation and DNA repairs and to study the role of endogenous Dach1 in tumorigenesis in vivo.