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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
- Mowat, M.R. p53 in tumor progression:
life, death, and everything. Adv.
Cancer Res. 74, 25-48
(1998). PMID
9561266
- 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
- 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
- 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
- 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
- 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).
- 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
- 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
- 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
Lab Members:
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