One of the major focuses of our lab is to elucidate the molecular
mechanisms of cancer initiation and progression, specifically through
the analysis of the PTEN tumor suppressor that is a major tumor suppressor
gene inactivated in cancers. Subsequent to unraveling its structure,
we investigate the biochemical pathways and molecular mechanisms responsible
for PTEN’s involvement in cancer cell proliferation and invasiveness.
The regulation of PTEN’s tumor suppressor function by its recruitment
to macromolecular protein complexes is one of the major projects in
my laboratory.
Concomitantly, we are investigating how the Neurofibromatosis 2 protein
and related molecules from the same protein family
(ERM –ezrin, radixin, moesin) impact the pathogenesis and invasiveness
of glioblastoma. We recently found that EBP50 (ERM-binding phophoprotein
50), an adaptor molecule that binds to NF2-ERM proteins, is necessary
for their organization at the apical membrane of specialized polarized
epithelial cells. EBP50 is mutated in human breast cancer and we are
pursuing its role in brain tumors by using EBP50(-/-) mutant mice
generated in the lab.
Overall, the projects in the lab involve techniques in protein biochemistry
and cellular biology, and the analysis and generation of knock-out
mice.
Recent publications
- Takahashi Y, Morales FC, Kreimann EL,
Georgescu M-M. (2006) PTEN tumor suppressor associates
with NHERF proteins to attenuate PDGF receptor
signaling. The EMBO Journal, 25:
910-920.
- Morales,
F., Takahashi, Y., Kreimann, E., and Georgescu,
M.-M. (2004) Ezrin-radixin-moesin
(ERM)-binding phosphoprotein 50 organizes ERM
proteins at the apical membrane of polarized
epithelia. Proc. Natl.
Acad. Sci. USA 101:17705-17710.
- Sumitomo,
M., Iwase, A., Navarro, D., Zheng, R., Kaminetzky,
D., Shen, R., Georgescu, M.-M.*,
and Nanus, D*. (2004) Synergy in tumor suppression
by direct interaction of Neutral Endopeptidase
with PTEN. Cancer Cell, 5:67-78. *Equal contribution.
- Radu,
A., Neubauer V., Akagi, T., Hanafusa, H., and Georgescu,
M.-M. (2003)
PTEN induces cell-cycle arrest by decreasing
the protein expression and nuclear localization
of cyclin D1. Mol. Cell.
Biol., 23:6139-6149.
- Georgescu MM, Kirsch
KH, Kaloudis P, Yang H, Pavletich NP, Hanafusa
H (2000) Stabilization and productive position
roles of the C2 domain of PTEN tumor suppressor. Cancer
Res, 60(24):7033-7038.
- Zhong H, Chiles K, Feldser
D, Laughner E, Hanrahan C, Georgescu MM,
Simons JW, Semenza GL (2000) Modulation of
hypoxia-inducible factor 1alpha expression
by the epidermal growth factor/phosphatidylinositol
3-kinase/PTEN/AKT/FRAP pathway in human prostate
cancer cells: implications for tumor angiogenesis
and therapeutics. Cancer
Res, 60(6):1541-1545.
- Lee JO, Yang H, Georgescu
MM, Di Cristofano
A, Maehama T, Shi Y, Dixon JE, Pandolfi P, Pavletich
NP (1999) Crystal structure of the PTEN tumor
suppressor: implications for its phosphoinositide
phosphatase activity and membrane association.
Cell, 99(3):323-334.
- Georgescu MM,
Kirsch KH, Akagi T, Shishido T, Hanafusa H
(1999) The tumor-suppressor activity of PTEN
is regulated by its carboxy-terminal region. Proc
Natl Acad Sci USA, 96(18):10182-10187.
- Georgescu MM,
Kirsch KH, Sishido T, Zong C, Hanafusa H (1999)
Biological effects of c-Mer receptor tyrosine
kinase in hematopoietic cells depend on the
Grb2 binding site in the receptor and activation
of NF-kappaB. Mol Cell
Biol, 19(2):1171-1181.
Mailing Address:
Department of Molecular Genetics, Unit 1006
U.T. M. D. Anderson Cancer Center
1515 Holcombe Boulevard
Houston, TX 77030
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