Research Interests:

One common characteristic of cancer cells is the loss of cell cycle checkpoint controls. These checkpoint controls function to allow cells to stop dividing and to repair damage to their DNA. A major player in the cell's checkpoint control is the p53 tumor suppressor gene, the most frequently mutated gene in human tumors.  Research in my laboratory is focused on the understanding the mechanisms of p53 cell cycle control.  We are also trying to learn which drugs can overcome these checkpoint controls in lung cancer cells to make tumors more sensitive to treatment. Cancer cells with a mutant p53 gene are more sensitive to chemotherapy and radiation when also treated with drugs that inhibit the cell's checkpoint controls.

Another area of research in my laboratory is the study of programmed cell death or apoptosis, a form of cell suicide. As a result of genetic changes, cancer cells have a reduced or slowed ability to undergo apoptosis which can also make them more resistant to anti-cancer drug treatment.  To better understand programmed cell death, we have taken a genetic approach. Several mutant cell lines have been isolated that are defective in apoptosis.  This was done by using a specially constructed virus that after it infects a cell can interfere with the genes that control cell death.  The underlying genes disrupted in the mutant cell lines by the virus are now being studied to understand their role in programmed cell death. By understanding the genetic basis of resistance to cell death, completely new treatments can be devised.

Recent Publications

1. Mowat, M.R. p53 in tumor progression: life, death, and everything. Adv. Cancer Res. 74, 25-48 (1998). PMID 9561266
2. Mowat, M.R. and Stewart, N. Mechanisms of cell cycle blocks at the G2/M transition and their role in differentiation and development. Prog. Mol. Subcell. Biol. 20:73-100 (1998). PMID 9928527
3. Navaratnam, S., Williams, G.J., Rubinger, M., Pettigrew, N.M., Mowat, M.R., Begleiter, A., and Johnston, J.B. Expression of p53 predicts treatment failure in aggressive non- Hodgkin's lymphomas. Leuk. Lymphoma 29, 139-144 (1998). PMID 9638983
4. Wang, J., Nielsen, P.E., Jiang, M., Cai, X., Fernandes, J.R., Grant, D.H., Ozsoz, M., Begleiter, A., and Mowat, M.. Mismatch-sensitive hybridization detection by peptide nucleic acids immobilized on a quartz crystal microbalance. Anal. Chem. 69, 5200-5202 (1997). PMID 9414622
5. Johnston, J.B., Daeninck, P., Verburg, L., Lee, K., Williams, G., Israels, L.G., Mowat, M.R., and Begleiter, A. P53, MDM-2, BAX and BCL-2 and drug resistance in chronic lymphocytic leukemia. Leuk. Lymphoma 26, 435-449 (1997). PMID 9389352
6. Wang, J., Rivas, G., Cai, X.H., Chicharro, M., Parrado, C., Dontha, N., Begleiter, A., Mowat, M., Palecek, E., and Nielsen, P.E. . Detection of point mutation in the p53 gene using a peptide nucleic acid biosensor. Anal. Chim. Acta 344, 111-118 (1997).
7. Stewart, N., G. Hicks, F. Paraskevas and M. Mowat. Evidence for a second cell cycle block at G2/M by p53 Oncogene 10: 109-115 (1995). PMID 7529916
8. Begleiter, A., L. Verburg, A. Ashique, K. Lee, L.G. Israels, M.R.A. Mowat and J.B. Johnston. Comparison of antitumor activities of 2-chlorodeoxyadenosine and 9- -arabinosyl-2- fluoroadenine in chronic lymphocytic leukemia and marrow cells in vitro. Leukemia 9: 1875-1881 (1995). PMID 7475278
9. Begleiter, A., K. Lee, L.G. Israels, M.R. A. Mowat and J.B. Johnston. Chlorambucil induced apoptosis in chronic lymphocytic leukemia (CLL) and its relationship to clinical efficacy. Leukemia 1: S103-6 (1994). PMID 8152273

PubMed Listed Publications