Title:   
Full Professor 

Institute:
University of Toronto

Department:  
Medical Biophysics

Province:
Ontario

Training:  
Fellowship, Harvard Medical School, Boston, MA, USA
Neurosurgery, Toronto General Hospital, Toronto, Ontario, Canada
MSc, Institute of Medical Science, University of Toronto, Toronto, Ontario, Canada
MD, University of Toronto, Toronto, Ontario, Canada

Research interests:
Molecular Neuro-oncology (CNS & PNS), Aberrant Signal Transduction, Glioma Metabolism, Angiogenesis and Tumor Microenvironment, Transgenic Models, Biomarkers
 
Recognitions:
Victor Levin Award, Society of Neurooncology, 2010
Lister Prize, University of Toronto, 2009  

Career highlights:
Demonstration of aberrant Ras activation in malignant gliomas and development of transgenic models based on this; demonstration that Hexosekinase II is an important aberrant regulator of aerobic glycolysis in malignant gliomas, with implications in tumor growth and therapeutic sensitivity; demonstration of how novel genetic alterations in human gliomas can be obtained by gene discovery experiments on relevant transgenic models.
 

Research Projects

Project title: 
Aberrations in EGFR in Human GBMs: Novel Diagnostic and Biomarker Strategies

Funding period:  
2010-2012

Program:
Operating Grant (Basic Research)

Summary:
Therapies targeting specific molecular alterations in conjunction to non-targeted therapies are the future of cancer therapeutics. However, initial clinical trial results have been met with limited success, especially in tumors such as Glioblastoma multiforme (GBM) where there is no one singular molecular alteration in all tumors that can be targeted. Current strategies using antibody based evaluation of these targets in the specimens have fallen short and cannot be readily repeated with biopsies for followup in GBMs. One such highly prevalent target already undergoing clinical evaluation in GBMs is Epidermal Growth Factor Receptor (EGFR). Here we propose novel diagnostic and non-invasive assays on sera and plasma of GBM patients, the techniques and proof-of-principles which we have already published. We believe these assays will facilitate early identification and follow-up of response of GBMs to biological therapies against EGFR. These assays can easily be extended to other biological targets of GBMs and other human cancers.

CRS publications:

Gajadhar, A, Guha, A: A Proximity Ligation based Epitope-Tagging expression assay for detection of in situ Dimerized Receptor Tyrosine Kinases Biotechniques 2010. Vol. 48 (2 ), 351-57

Wei, Q, Clarke, L, Scheidenhelm, DK, Qian, B, Tang, A, Sabha, N, Karim, Z, Bock, N, Reti, R, Swoboda, R, Purev, E, Lavoie, J-F, Bajenaru, MJ, Shannon, P, Herlyn, D, Kaplan, D, Henkelman, RM, Gutmann, DH, Guha, A: High-Grade Glioma Formation Results from Postnatal Pten Loss or Mutant Epidermal Growth Factor Receptor Expression in a Transgenic Mouse Glioma Model. Cancer Research. 2006 Aug1: 66(1): 7429-7437

Cheon SS, Wei Q, Youn A, Guha A, Alman BA.  Transforming growth factor-beta regulates dermal wound healing through regulation of beta-catenin. FASEB J. 2006 Apr;20(6):692-701

Past CRS projects: 
 
2000 Mouse astrocytoma model:  Astrocyte specific knockout of PTEN / MMAC1.