Maria-Magdalena Georgescu MD, MSc, PhD

Dr. Georgescu is one of the few investigators with an extensive expertise in both molecular neuro-oncology and neuropathology. She directs very exciting and original neuro-oncology and neuropathology research projects with major relevance to brain tumor marker discovery. The focus of her research is the understanding of the pathogenesis of glioma. Dr. Georgescu is renowned for her pioneering work in the regulation of PTEN tumor suppressor and activation of the PI3 kinase in glioblastoma. Notably, she defined a network of tumor suppressors controlling glioblastoma growth and invasion formed by PTEN, NHERF1 and PHLPP. Her laboratory was the first to implicate NHERF1 mechanistically in cancer. This work was translated into clinic by establishing NHERF1 as progression marker in colorectal cancer and as diagnostic marker in ependymoma and other microlumen-forming CNS tumors. More recently, she devised an original model of diffuse glioma that recapitulates the human disease and constitutes an excellent source for deriving disease progression markers and for testing targeted therapies.

Biography:

2013 - 2015
UT Southwestern, Dallas, TX, Fellowship, Neuropathology
2011 - 2013
UT Southwestern, Dallas, TX, Resident, Anatomic Pathology
2001 - 2001
The Rockefeller University, New York, NY, Howard Hughes Medical Institute (HHMI) Associate, Laboratory of Apoptosis and Cancer Biology (Hermann Steller)
1996 - 2001
The Rockefeller University, New York, NY, Postdoctoral Fellow, Laboratory of Molecular Oncology (Hidesaburo Hanafusa)
1992 - 1996
Microbiology – Pasteur Institute, Paris, France, PhD
1991 - 1992
Cellular and Molecular Biology – Joseph Fourier University, Grenoble, France
1984 - 1990
Medicine – Carol Davila Medical School, Bucharest, Romania, MD

Employement:

2016 - Present
LSU Health Shreveport
2012 - 2016
West Virginia University, Department of Pathology
2009 - 2012
Charleston Area Medical Center, Pathology
1997 - 2009
University of South Alabama, Departments of Pathology, Pharmacology, and Center for Lung Biology

Previous Appointments:

2006 - 2011
Associate Professor – tenure, Departments of Neuro-Oncology and Genetics, UT MD Anderson Cancer Center, Houston, TX
2001 - 2006
Assistant Professor, Departments of Neuro-Oncology and Molecular Genetics, UT MD Anderson Cancer Center, Houston, TX
2001 - 2009
Adjunct Faculty Member, Laboratory of Apoptosis and Cancer Biology, The Rockefeller University, New York, NY
1990 - 1991
Physician, Division of Intensive Care, Municipal Hospital, Bucharest, Romania
1990 - 1991
Assistant Professor, Department of Physiology, Carol Davila Medical School, Bucharest, Romania

Board Certifications

2011 -
Anatomic Pathology
2011 -
Neuropathology

 

Awards and National Recognition

  • Internal Medicine and Surgery National Student Competition Award, Romania, 1989
  • National Fellowship for Best Results in Medicine, Romania, 1990
  • Fellowship (WHO V26/181), World Health Organization, 1992−1996
  • Postdoctoral Fellowship, Medical Research Council of Canada, 1996−2000
  • Postdoctoral Fellowship, National Cancer Institute, 1998−2001
  • Cell Cycle-Keystone Symposia Scholarship, 2001
  • Postdoctoral Fellowship, Howard Hughes Medical Institute (HHMI), 2001
  • Business Professional Women of Texas Award, Business Professional Women of Texas, 2004−2005
  • Excellence in Research Mentorship Certificate, 2005
  • DOD, Congressionally Directed Medical Research Programs on Neurofibromatosis, Member, 2006
  • New Jersey Commission on Cancer Research, Ad Hoc Member, 2007
  • Cancer Research UK, Ad Hoc Member, 2007
  • Robert M. Chamberlain Distinguished Mentor Award Nominee, The University of Texas M. D. Anderson Cancer Center, 2008
  • NIH, ZRG1 BST-J (51) Study Section, Member, 2008
  • DOD, Congressionally Directed Medical Research Programs on Neurofibromatosis, Member, 2008
  • NIH, ZRG1 BST-J (51) Study Section, Member, 2010
  • DOD, Congressionally Directed Medical Research Programs on Neurofibromatosis, Member, 2011

Publications

1) Foundation of the new field of PTEN tumor suppressor regulation in cancer

Georgescu MM, Kirsch KH, Akagi T, Shishido T, Hanafusa H. The tumor suppressor activity of PTEN is regulated by its carboxyl-terminal region. Proc Natl Acad Sci USA, 96:10182-7, 1999.

Georgescu MM, Kirsch KH, Kaloudis P, Yang H, Pavletich NP, Hanafusa H. Stabilization and productive positioning roles of the C2 domain of PTEN tumor suppressor. Cancer Res, 60:7033-8, 2000.

Radu A, Neubauer V, Akagi T, Hanafusa H, Georgescu MM. PTEN induces cell-cycle arrest by decreasing the protein level and nuclear localization of cyclin D1. Mol Cell Biol, 23:6139-49, 2003.

Sumitomo M, Iwase A, Navarro D, Zheng R, Kaminetzky D, Shen R, *Georgescu MM, *Nanus D. Synergy in tumor suppression by direct interaction of Neutral Endopeptidase with PTEN. Cancer Cell, 5:67-78, 2004. *equal contribution

Georgescu MM. PTEN tumor suppressor network in PI3K-Akt pathway control. Genes Cancer 1(12), 1170-7, 2010

2) Establishment of NHERF1/EBP50 as signaling molecule in cancer

Morales FC, Takahashi Y, Kreimann EL, Georgescu MM. Ezrin-radixin-moesin (ERM)-binding phosphoprotein 50 (NHERF1/EBP50) organizes ERM proteins at the apical membrane of polarized epithelia. Proc Natl Acad Sci USA, 101:17705-10, 2004.

Takahashi Y., Morales FC, Kreimann EL, Georgescu MM. PTEN tumor suppressor associates with NHERF proteins to attenuate PDGF receptor signaling. EMBO J, 25(4): 910-920, 2006.

Morales FC, Takahashi Y. Momin S, Adams H, Chen X, Georgescu MM. NHERF1/EBP50 head-to-tail intramolecular interaction masks the association with PDZ-domain ligands. Mol Cell Biol, 27:2527-37, 2007.

Kreimann EL, Morales FC, Takahashi Y, Adams H, Liu T-J, McCrea PD, Georgescu MM. Cortical stabilization of b-catenin contributes to NHERF1/EBP50 tumor suppressor function. Oncogene, 26:5290-9, 2007.

Georgescu MM, Morales FC, Molina JR, and Hayashi Y. Roles of NHERF1/EBP50 in cancer. Curr Mol Med 8(6):459-68, 2008

Georgescu MM, Cote G, Agarwal NK, White CL. NHERF1/EBP50 controls morphogenesis of 3D colonic glands by stabilizing PTEN and ezrin-radixin-moesin proteins at the apical membrane. Neoplasia 16(4):365-74, 2014

Georgescu MM, Gagea M, Cote G. NHERF1/EBP50 suppresses Wnt-b-catenin pathway driven intestinal neoplasia. Neoplasia 8:512-23, 2016

3) Generation of mouse models and discovery of a tumor suppressor protein network controlling glioblastoma growth.

Molina JR, Hayashi Y, Stephens C, Georgescu MM. Invasive glioblastoma cells acquire stemness and increased Akt activation. Neoplasia, 12(6):453-63, 2010.

Molina JR, Morales FC, Hayashi Y, Aldape K, Georgescu MM. Loss of PTEN binding adapter protein NHERF1 from plasma membrane in glioblastoma contributes to PTEN inactivation. Cancer Res, 70(17):6697-703, 2010.

Molina JR, Agarwal NK, Morales FC, Hayashi Y, Aldape K, Cote G, Georgescu MM. PTEN, NHERF1 and PHLPP form a tumor suppressor network that is disabled in glioblastoma. Oncogene, 31(10):1264-74, 2012.

Agarwal NK, Zhu X, Gagea M, White CL, Cote G, Georgescu MM. PHLPP2 suppresses the NF-kB pathway by inactivating IKKb kinase. Oncotarget 5(3):815-823, 2014.

4) Design of tumor markers for clinical use.

Hayashi Y, Molina JR, Hamilton SR, Georgescu MM. NHERF1/EBP50 is a new marker in colorectal cancer. Neoplasia 12(12):1013-22, 2010.

Morales FC, Molina JR, Hayashi Y, Georgescu MM. Overexpression of ezrin inactivates NF2 tumor suppressor in glioblastoma. Neuro Oncol, 12(6):528-39, 2010.

Zhu X, Morales FC, Agarwal NK, Dogruluk T, Gagea M, Georgescu MM. Moesin is a glioma progression marker that induces proliferation and Wnt/b -catenin activation via interaction with CD44. Cancer Res, 73:1142-55, 2013.

Georgescu MM, Yell P, Mobley BC, Shang P, Georgescu T, Wang SH, Canoll P, Hatanpaa KJ, White CL, Raisanen JM. NHERF1/EBP50 is an organizer of polarity structures and a diagnostic marker in ependymoma. Acta Neuropathol Commun, 3:11, 2015.

Georgescu MM, Mobley BC, Shang P, Zhu X, Lehman N, Rajaram V, Hatanpaa KJ, Timmons CF, Raisanen JM. NHERF1/EBP50 and NF2 as diagnostic markers for choroid plexus tumors. Acta Neuropath Commun, 4:55, 2016

5) Definition of new clinicopathologic entities

Georgescu MM, Delpeyroux F, Tardy-Panit M, Balanant J, Combiescu M, Combiescu AA, Guillot S, Crainic R. High diversity of poliovirus strains isolated from the central nervous system from patients with vaccine-associated paralytic poliomyelitis. J Virol, 68(12):8089-101,1994.

Georgescu MM, da Cunha Pinho M, Richardson, TE, Torrealba J, Buja LM, Milewicz DM, Raisanen JM, Burns DK. The defining pathology of the new clinical and histopathologic entity ACTA2-related cerebrovascular disease. Acta Neuropathol Commun, 3:81, 2015.