Together with J. Dirk Iglehart, I have established
a program of research in the molecular biology and
genetics of breast cancer. We are particularly interested
in understanding the genetic abnormalities that lead
to the disease. We have recently focused on genes
that control cell growth at the level of the cell
cycle machinery. These critical regulatory genes include
p53, BRCA1, and BRCA2. We have studied the role of
p53 in breast cancer for many years and are presently
trying to understand how the p53 protein is regulated
after a cell sustains DNA damage. The p53/DNA damage
pathway may be central in determining whether a cell
becomes neoplastic after being exposed to carcinogens
and radiation. We were involved in the recent identification
of both breast cancer susceptibility genes, BRCA1
and 2. Their discovery has prompted an intense investigation
into their structure, function, and role in non-hereditary
breast cancer. We are involved in each of these aspects
of research with both of these genes. The sequence
of BRCA1 and 2 provide only the barest clues as to
what these genes actually do. We have disovered that
both of these genes are regulated during the cell
cycle in a manner that is very similar to p53. Therefore,
we are investigating whether, like p53, BRCA1 and
2 are also involved in controlling progression through
the cell cycle, particularly entry into the DNA synthetic
phase. Since neither BRCA1 or 2 are frequently mutated
in non-hereditary breast cancer, we are also determining
whether there are other ways in which their function
may be interrupted in this more common form of the
disease. All aspects of this research are available
to graduate students who choose our laboratory.
