The laboratory of Jan van Deursen, Ph.D., is interested in the molecular basis of human cancer. Dr. van Deursen's approach is to study the normal and malignant functions of genes implicated in human cancer at the level of the cell and the entire organism.
Mitotic checkpoint function and chromosomal stability. Dr. van Deursen's research team is interested in some of the basic molecular mechanisms that regulate chromosome number stability in mammalian cells.
Understanding these regulatory mechanisms is important, as abnormalities of chromosome number are a hallmark of the vast majority of human cancers. A subset of these cancers is associated with mutations in genes encoding for mitotic checkpoint proteins such as BUB1, BUBR1, BUB3 or MAD2. These checkpoint proteins are part of an intricate regulatory mechanism that prevents aneuploidy by delaying sister chromatid separation until all chromosomes are properly attached to the mitotic spindle apparatus and aligned at the metaphase plate.
The major objective of work in this area is to understand the role of distinct mitotic checkpoint proteins in normal and neoplastic growth. Much of Dr. van Deursen's research utilizes genetically engineered mice, in which individual mitotic checkpoint genes have been mutated. His research team also addresses several basic questions of mitotic checkpoint regulation using somatic tissue culture cells.
Transcriptional coactivators in normal and neoplastic growth. Another major objective is to understand the role of CBP and p300 in normal and malignant cell growth. CBP and p300 are highly related transcriptional coactivators that seem to modulate the functions of a wide variety of transcription factors.
Recent studies have provided genetic evidence that CBP and p300 could act as tumor suppressor genes in a variety of human tissues, including breast, colon and lung. One idea is that loss of CBP or p300 function could simply lead to derailment of factors that are required for the proper control of cell growth, differentiation and death. The simplest way to demonstrate the tumor suppressor activity of CBP and p300 would be to genetically disrupt their genetic loci in the mouse and monitor the resulting animals for tumor formation. However, both CBP and p300 are essential for growth and development, and cause similar embryonically lethal phenotypes when completely disrupted in the mouse.
Dr. van Deursen's team is trying to bypass this problem using CBP and p300 conditional knockout mice, with an emphasis on testing whether disruption of CBP and p300 in intestinal and mammary gland epithelium leads to tumor formation.
Significance to patient care
Through his research on the genetic functions of tumor growth and suppression, Dr. van Deursen works toward a better understanding of the causes and origins of cancer, with the ultimate goal of developing tools for prediction, prevention or treatment of the disease.