Brain Tumor Research Alliance Members
 

 Bergen, Hugobergen

Associate Professor, Department of Human Anatomy and Cell Science
College of Medicine, Faculty of Health Sciences, University of Manitoba


My main areas of research interests are twofold.  I have a longstanding interest in the area of hormonal and metabolic regulation of neural activity and how genetic variability influences neural responses to circulating factors involved in metabolism.  The model system I use is the neuroendocrine regulation of energy balance with an emphasis on how changes in neural responsiveness can lead to deficits in metabolism.  To study this I have developed animal models of metabolic dysregulation and have used quantitative in situ hybridization and immunocytochemistry to delineate the importance of specific neuropeptides in the brain on metabolism. 

More recently I have developed an interest in understanding the basis for chemoresistance in glioblastoma.  Using my expertise in small animal stereotactic surgery I am interested in developing in vivo models of glioblastoma that can be used to test the efficacy of new treatments for glioblastoma.  In particular, I am interested in developing strategies to overcome the chemoresistance that occurs with many chemotherapeutics.

PubMed Publications


Beiko, Jason

jason beiko 2015

Medical Doctor, Department of Neurosurgery, Health Sciences Centre

Website

My main areas of research interests are twofold.  I have a longstanding interest in the area of hormonal and metabolic regulation of neural activity and how genetic variability influences neural responses to circulating factors involved in metabolism.  The model system I use is the neuroendocrine regulation of energy balance with an emphasis on how changes in neural responsiveness can lead to deficits in metabolism.  To study this I have developed animal models of metabolic dysregulation and have used quantitative in situ hybridization and immunocytochemistry to delineate the importance of specific neuropeptides in the brain on metabolism. 

More recently I have developed an interest in understanding the basis for chemoresistance in glioblastoma.  Using my expertise in small animal stereotactic surgery I am interested in developing in vivo models of glioblastoma that can be used to test the efficacy of new treatments for glioblastoma.  In particular, I am interested in developing strategies to overcome the chemoresistance that occurs with many chemotherapeutics.

PubMed Publications


 marc del bigio photoDel Bigio, Marc

Professor, Department of Pathology

Canada Research Chair in Developmental Neuropathology
Department of Human Anatomy and Cell Science
College of Medicine, Faculty of Health Sciences, University of Manitoba

 Dr. Del Bigio is a clinical and experimental neuropathologist whose primary research concerns brain disorders of childhood.

 

PubMed Publications


 marco essig photoEssig, Marco

Professor, Department of Radiology
Medical Director, Winnipeg Regional Health Authority
College of Medicine, Faculty of Health Sciences, University of Manitoba

Email: messig@exchange.hsc.mb.ca


Integration of functional imaging techniques like diffusion tensor imaging (DTI), dynamic susceptibility contrast MRI (DSC- MRI), dynamic contrast-enhanced MRI (DCE-MRI), and proton magnetic resonance spectroscopy (HMRS), into neuroimaging protocols which will provide information about white matter tract disruption by tumor infiltration, tumor neovascularization, tumor vascular permeability, and tumor tissue energy metabolism, respectively. Identifying the most invasive and proliferative region of a tumor will determine the appropriate site for biopsy, in order to obtain a tissue specimen that accurately reflects the severity of a patient’s malignancy. This in turn, directly impacts patient management and choice of therapy.

Correlation of functional imaging techniques with histological and molecular characteristics of tumors. This will be enabled by direct – targeted biopsy based on the imaging characteristics of brain tumors. Use of new contrast mechanisms in the diagnostic work-up of brain tumors and to correlate the achieved information with outcome measures and to define prognostic factors.

spencer gibson photoGibson, Spencer

Professor, Departments of Biochemistry and Immunology
Director of Manitoba Institute of Cell Biology & Cancer Care Manitoba
College of Medicine, Faculty of Health Sciences, University of Manitoba

Email: spencer.gibson@umanitoba.ca


Regulation of cell survival and death signaling in Glioblastoma tumors. Bcl-2 family members regulate cell death (apoptosis) and cell survival. They are divided into three groups: anti-cell death, pro-cell death and regulatory BH-3 only proteins. Under normal conditions, anti-cell death protein Bcl-2 binds to the pro-death proteins Bax and Bak preventing cell death. Under stress conditions, pro-cell death members become activated by binding to BH3-only members or BH3 only members bind to Bcl-2 thereby allowing activation of Bax and Bak. Bcl-2/E1B 19kDa interacting protein (BNIP3) is a BH-3 only Bcl-2 family member that its expression is increased in GBM tumors within hypoxic regions. Upon forced over-expression, BNIP3 localizes to the mitochondria and induces cell death. Bcl-2 binds to BNIP3’s TM domain thereby preventing BNIP3 mitochondrial localization and cell death. One question that remains unanswered is why BNIP3 is expressed at high levels in glioblastoma (GBM) tumors when it induces cell death in cancer cell lines. We are currently investigating the role other Bcl-2 family members in regulation BNIP3 cell death function. In addition BNIP3 has been shown to regulate autophagy (self-eating) leading to cell survival. We will also investigate the role autophagy plays in regulating BNIP3 function. By understanding the role of BNIP3 proteins in GBM, more effective therapies could be developed.
 
grant hatch photo Hatch, Grant

Professor, Department of Pharmacology and Therapeutics, Biochemistry & Medical Genetics
Canada Research Chair of Molecular Cardiolipin Metabolism
Manitoba Institute of Child Health
College of Medicine, Faculty of Health Sciences, University of Manitoba


In my research program we are examining the regulation of the metabolism of the polyglycerophospholipid cardiolipin (bis-(1,2-diacyl-sn-glycero-3-phospho)-1',3'-sn-glycerol; abbreviated CL). Specifically we are studying the regulation of CL biosynthesis and remodeling in the heart and in mammalian tissues and cells.

PubMed Publications


aleksandra Gloglowska, Aleksandra

Instructor, Department of Human Anatomy and Cell Science, College of Medicine, Faculty of Health Sciences, University of Manitoba

Dr. Glogowska is interested in studying effect of proEGF like ligands in the ubiquitin-proteasome system in brain cancer.  Her PHD work showed important function of pro EGF domains in regulation of proteolytic degradation of ErbB1/2 effecting major cell cycle molecules and leading to inhibition of cancer cells proliferation and migration. Over-expression of EGFR in brain tumors (oligodendrogliomas, glioblastomas) identifies them as targets for the actions of EGF-like ligands. Pro EGF has been known to affects tumor cell growth, differentiation and metastasis. Amplification and ligand-induced activation of EGFR correlates with increased in-vitro tumor cell migration, matrix degradation and enhanced in-vivo tissue invasiveness.
Knowledge of the regulatory mechanisms that control the function of ubiquitin-proteasome system is critical to design of new or use of already existing inhibitors with the aim of inducing ubiquitin-proteasome system related anticancer effect.

PubMed Publications


 saeidGhavami, Saeid

Assistant Professor, Department of Human Anatomy and Cell Science
College of Medicine, Faulty of Health Sciences, University of Manitoba

Email: saeid.ghavami@umanitoba.ca


Website

The mevalonate (MA) cascade not only plays a central role in cholesterol biosynthesis via squalene metabolism, but is also the precursor of several isoprenoid derivatives, including farnesylpyrophosphate (FPP) and geranylgeranylpyrophosphate (GGPP). These isoprenoids are essential for posttranslational prenylation of a number of proteins, including the small GTPases of the Ras and Rho families. FPP and GGPP are required for Ras farnesylation and Rho geranylgeranylation, respectively. Both Ras and Rho are critical components of diverse intracellular signaling pathways, and prenylation is essential for their membrane localization and function in many cell types. The statin drugs (“statins”), “geranylgeranyltranferase inhibitors”, and “farensyltransferase inhibtors” are different classes of compounds that inhibit 3-hydroxy-3-methyl-glutaryl-CoA reductase (HMGR), geranylgeranylation, and farnesylation, respectively. There is a growing recognition of the importance of the MA cascade in the regulation of heart and lung diseases, and cancer in particular.  

In recent years, I have been working on different aspects of the MA cascade’s regulation and its importance in different diseases including lung disease, heart disease, and cancer. Given the clinical relevance of this pathway, and the inhibitors available to modulate it, I plan to take the lead to investigate about the importance of this pathway in brain tumors.  I focus on the importance of MV cascade in brain tumor chemo-resistance, developing combination therapy (HMGR inhibitors, geranylgeranyl trasnferase inhibitors, and farnesyl transferase inhibitors) and importance of this pathway in differentiation of brain stem cells.

PubMed Publications


hao ding Ding, Hao

Associate Professor, Department of Biochemistry & Medical Genetics
College of Medicine, Faculty of Health Sciences, University of Manitoba

Email: hao.ding@umanitoba.ca

Website

My lab is focusing on understanding the role of PDGF-C and RTL1 in development. Currently, with our several developed mouse models, we found that these two genes could be expressed in cerebellar stem cells. RTEL1 knockout in this group of stem cells can induced medulloblastoma indicating that cerebellar stem cells are a cellular source for this common pediatric brain tumor. In addition, RTEL1 could be part of a defense system to protect genomic stability in these stem cells.

In the last decade, my lab has generated many transgenic animal approaches at the University of Manitoba which can be valuable genetic tools for uncovering gene functions during development and in tumorigenesis. This includes the research activities on brain tumor research at the University of Manitoba.

sabine hombachHombach-Klonisch, Sabine

Associate Professor, Department of Human Anatomy and Cell Science
Department of Obstetrics, Gynecology & Reproductive Medicine
College of Medicine, Faculty of Health Sciences, University of Manitoba

Email: sabine.hombach-klonisch@umanitoba.ca


In my research, I want to identify the molecular determinants and mechanisms within the local tumor environment that regulate cancer cell invasiveness, survival and chemoresistance in brain tumors. I am studying the defense mechanisms elicited by brain tumor cells in response to oxidative and chemotherapeutic stress. The molecular families I am particularly interested in include the C1q- tumor necrosis factor-like family of peptides and the oncofetal High Mobility Group A2 (HMGA2) protein which my group identified as new players in brain cancer.

My lab is studying the role of relaxin-like peptides and novel C1q- tumor necrosis factor related proteins and their membrane-anchored G protein-coupled receptor (RXFP1) in promoting cancer cell invasion into normal brain tissue. We investigate the molecular signaling pathways and target molecules induced by RXFP1 activation which promote tissue invasion and survival of brain tumor (stem-like) cells. My team develops specific inhibitors to block RXFP1 function in human brain cancer cells.

The nuclear cancer stem cell factor High Mobility Group A2 (HMGA2) promotes brain tumor cell plasticity, cell migration and modulates key DNA repair signaling events. We identified new HMGA2 interacting proteins under conditions of oxidative and chemotherapeutic stress and utilize this information to develop new therapeutic strategies to specifically target and destroy brain tumor cells.

PubMed Publications


 Sachin Katyal photoKatyal, Sachin

Assistant Professor and Senior Scientist, Department of Pharmacology and Therapeutics
College of Medicine, Faculty of Health Sciences, University of Manitoba
Manitoba Institute for Cell Biology, Cancer Care Manitoba

 
Modulating DNA damage repair pathways in the treatment of malignant brain tumours.

My current research focus is to identify ways to specifically alter cellular DNA repair pathways in pediatric and adult brain tumours in order to improve upon current cancer therapeutic strategies. These studies seek to understand the relationship between normal neuronal development, neurodegeneration, how dysregulation of these processes leads to cancer and identification of novel treatment avenues.

Areas of interest: DNA damage and repair, DNA Topoisomerases, neuronal development, neurodegeneration, neuro-oncology, molecular carcinogenesis, chemotherapeutics, radiotherapeutics, synthetic lethality.

PubMed Publications


thomas klonisch photoKlonisch, Thomas

Professor and Head, Department of Human Anatomy and Cell Science
Department of Medical Microbiology & Infectous Diseases, Department of Surgery
Director of the Histomorphology & Ultrastructural Imaging Platform
Director of Glioma Cell Resource
College of Medicine, Faculty of Health Sciences, University of Manitoba

Email: thomas.klonisch@umanitoba.ca

Brain tumors represent a highly dynamic, interactive and heterogeneous cellular complex. Brain tumor cell plasticity, resistance to therapeutics, metastasis and recurrence are seemingly different and unconnected processes. These cellular events are the result of a complex interplay between brain tumor cells and their local microenvironment.

My brain tumor research is aimed at identifying common themes that connects these cellular events and provides us with a more integrated view of the molecular and genetic events that promote the formation and propagation of brain tumors. In close collaboration with my clinical and basic science colleagues, our team aims at translating new knowledge gained in our research lab into new therapeutic strategies to eradicate brain tumor. Our brain tumor research utilizes advanced 3D high-resolution imaging tools, molecular/ cell biology functional tools and analysis and animal models. We use human brain tumor cells isolated from patients and animal models to investigate mechanisms of chemoresistance in brain tumor cells. Based on this, we devise new targeted chemotherapeutic strategies and test for more effective drug combinations with the potential for synthetic lethality in human brain cancer cells.

Glioma initiating cells (GIC) represent a small population of highly adaptable cells within a brain tumor that promotes glioma formation. GIC impact on the development of therapeutic resistance and are important in fatal tumor metastasis and recurrence. My research team studies the molecular and genomic mechanisms that regulate these brain tumor phenotypes. We want to identify molecular indicators that can be used to direct our therapeutic strategies.

PubMed Publications


gadji macoura photoGadji, Macoura

Assistant Professor, Faculty of Pharmacy
Affiliate Researcher, Manitoba Institute for Cell Biology, Cancer Care Manitoba
Department of Physiology
College of Medicine, Faculty of Health Sciences, University of Manitoba

Master-Assistant Professor at Cheikh Anta Diop University of Dakar (UCAD)

Email: macoura.gadji@umanitoba.ca

Website TBA

 Cytogenetics, chromosomal instability (CIN) and genomic instability (GIN) of brain tumors (gliomas) ; Nuclear remodeling and 3D nuclear telomere architecture in gliomas. My previous work contributed to the assessment of 1p/19q deletion by FISH as a biomarker of oligodendrogliomas and oligoastrocytomas (Gadji M et al., Cancer Genet Cytogenet. 2009). Using the nuclear architecture or nuclear telomere remodelling, we have identified new patient subgroups that were previously unknown in adult glioblastoma (due to the absence of diagnostic tools). We identified subgroups of patients with short-term, intermediate and long-term survival in glioblastoma (Gadji et al., 2010, Neoplasia.; Gadji et al., Adv Cancer Res. 2011). We proposed that nuclear telomere architecture as a novel and highly efficient biomarker of glioblastoma that need to be validated.  Our ongoing work determined the potential molecular mechanism of recurrence in oligodendrogliomas and oligoastrocytomas by studying the nuclear telomere remodeling in these diseases (Gadji et al., 2013, Neuropathology; second manuscript in preparation).

sabine mai photoMai, Sabine

Professor, Department of Physiology
, Department of Biochemistry & Medical Genetics
Department of Human Anatomy & Cell Science
Manitoba Institute for Cell Biology, Cancer Care Manitoba
College of Medicine, Faculty of Health Sciences, University of Manitoba
 

Email: sabine.mai@umanitoba.ca

My research focuses on mechanisms of c-Myc oncogene dependent locus-specific and karyotypic instability, c-Myc-dependent tumour development in vivo (using the mouse model of plasmacytoma) and on understanding the three-dimensional (3D) nuclear organization of the mammalian genome in normal, immortalized and tumour cells. 

PubMed Publications


marshall pitz photoPitz, Marshall

Assistant Professor, Department of Internal Medicine

Medical Oncologist; Chair, CNS Disease Site Group, Cancer Care Manitoba

College of Medicine, Faculty of Health Sciences, University of Manitoba

Email: marshall.pitz@cancercare.mb.ca

Website TBA

I am a medical oncologist and Chair of the Brain Tumour Disease Site Group at CancerCare Manitoba. His research expertise is in clinical, epidemiology, and translational methods. I have worked on a number of retrospective reviews and translational programs in addition to serving as a member of the Brain Tumour Executive Committee and Investigational New Drug Executive Committee at the National Cancer Institute of Canada Clinical Trials Group.

PubMed Publications


 stetefeld Stetefeld, Jörg

Professor, Associate Head, Department of Chemistry, Department of Microbiology
Canada Research Chair in Structural Biology
Adjunct Associate Professor, Department Biochemistry and Medical Genetics
College of Medicine, Faculty of Health Sciences, University of Manitoba

Email: jorg.stetefeld@umanitoba.ca

Website


The primary goal of my research team is to understand in detail the structure-function relationship of proteins involved in neuronal axon guidance and intercellular signaling.  We are mainly focused on signaling linked to catalytic turnover, the molecular mechanisms of chemo-attraction and chemo-repulsion and mechanisms of complex formations and signal transduction within the extracellular matrix.
To reveal the structural and functional basics of the underlying molecular aspects of signaling we use a combination of the biophysical techniques: X-ray crystallography in combination with Small-angle X-ray scattering (SAXS) and X-ray photo-electron spectroscopy (XPS), solution Nuclear magnetic resonance (NMR) spectroscopy and Electron Microscopy, several biophysical techniques  (Circular Dichroism (CD) spectroscopy, Dynamic Light Scattering (DLS), Analytical UltraCentrifugation (AUC), Isothermal Titration Calorimetry (ITC), Differential Scanning Calorimetry (DSC) and Fluorescence Resonance Energy Transfer (FRET) spectroscopy, and in vitro functional molecular biology and biochemical analysis.

Our long term goal is to develop a molecular understanding of target proteins at work. The research will provide new insights into basic mechanisms of how these proteins function, and applied science of great biotechnological and biomedical importance will be advanced.

PubMed Publications

Cancer Cell Article ScienceDirect


don miller photoMiller, Don

Professor, Department of Pharmacology & Therapeutics
College of Medicine, Faculty of Health Sciences, University of Manitoba

Email: donald.miller@umanitoba.ca


My laboratory is interested in blood-brain barrier (BBB) and blood-tumor barrier (BTB) structure and function. We are exploring two complementary paths. One is to identify and characterize approaches for improving the delivery of anticancer agents to the brain and tumor sites. Work in this area focuses on nanoparticle drug delivery platforms and transient disruption of BBB for delivery of both small and large molecular weight therapeutics. The second area of interest involves identifying cellular and molecular targets within the brain microvasculature that are involved in cancer metastasis to the brain. My laboratory uses a combination of cell culture BBB models as well as murine brain tumor models and multiple imaging modalities including MRI, near infrared fluorescence and optical imaging to quantitatively determine BBB and BTB permeability to solutes and therapeutics.
 
PubMed Publications
debbie swan

Swan, Debbie

Registered Nurse, Neurosurgery Clinic
for Drs. Berrington, West, Krcek and Kazina

Email: dswan@exchange.hsc.mb.ca

 Research interest/bio. to be announced soon.

 

 

 

 


geoffrey tranmer photoTranmer, Geoffrey

Assistant Professor
College of Pharmacy, Faculty of Health Sciences, University of Manitoba

Email: geoffrey.tranmer@umanitoba.ca


I am a synthetic organic chemist by training, with industrial experience developing pre-clinical drug candidates and imaging agents. My area of research interest is centered within the broad field of medicinal chemistry, at the intersection of synthetic organic chemistry and pharmacology, and focused on understanding the state of hypoxia in brain tumors, developing hypoxia-targeting cancer therapies, and the imaging of hypoxia and brain tumors. To date, synthetic organic chemistry has already had a significant impact on the fields of medicinal chemistry and neuroscience, with major advancements being applied towards developing new pharmaceutical therapies and for the study and manipulation of neurological systems. My research interests are largely focused on these main themes, and have an end goal of improving the process of drug discovery and facilitating innovation in brain tumor research.
 

tamra ogilvie photoWerbowetski-Ogilvie, Tamra

Assistant Professor, Department of Biochemistry & Medical Genetics and Physiology
Canada Research Chair in Neuro-oncology and Human Stem Cells
College of Medicine, Faculty of Health Sciences, University of Manitoba

Email: tamra.ogilvie@umanitoba.ca

Website TBA

My laboratory seeks to identify new molecular targets that regulate pediatric brain tumor progression. To accomplish this, my research program is divided into 2 major areas: 1. The early stages: Investigating the early molecular events in pediatric malignant brain tumorigenesis using human embryonic stem cells and their neural derivatives as a new model system.2. The late stages: Investigating medulloblastoma cellular heterogeneity and identifying new biomarkers for both tumor propagating and highly migratory cells using in vitro and in vivo models.

 PubMed Publications