Cancer arises from the accumulation of small changes (mutations) in different genes in our normal epithelial cells (for example in the prostate, breast or colon) that eventually result in uncontrolled proliferation of the cells. When normal epithelial cells divide, they require the normal function of many cellular proteins and nucleic acids at certain points in the cell-division process. Cancer cells use these same cellular factors for their proliferation and mis-regulation of these factors help them escape the restraints to proliferation.

Both normal and cancer cells require the actions of many enzymes (DNA replication factors) for copying the DNA in the chromosomes. A cell will stop dividing if it cannot copy its chromosomes or will divide incompletely replicated chromosomes and induce chromosomal damage. One area of research in my laboratory is to identify the factors necessary for DNA replication initiation and determine how they are regulated. We also identify the consequences of mis-regulation of these factors on genomic stability and the cell-cycle. In addition, we use modern tools of genomics to identify sites on human chromosomes that begin the process of DNA replication and how these sites change between different cells.

An independent area of research focuses on small RNAs present in our cells. MicroRNAs and other short RNAs are now known to have profound effects on gene expression and are hypothesized to affect cell proliferation. To study this process in detail we explore the role of microRNAs in inducing quiescence as proliferating myoblasts differentiate into mature muscle fibers. Androgen deprivation is the primary mode of therapy of advanced prostate cancer, and recurrence of the disease is associated with androgen-independence. Thus, we also study how microRNAs and other short RNAs change when androgen-dependent prostate cancer cells are induced to become quiescent by androgen deprivation. Collectively these studies will elucidate how microRNAs and other short RNAs influence cell proliferation.