Our Scientists

The Senior Scientists at the Research Institute are involved in a wide variety of research activities to understand the nature of cancer and blood disorders. Working in a transdisciplinary teams of clinicians, scientists, technicians, research nurses, trainees, and bioinformaticians, we bring together diverse skill sets to translate basic science discoveries into improved patient outcomes.

Cancer is complicated disease that affects nearly family. Through the use of our research platforms, we can investigate the role of genes to initiate, drive or terminate cancers, discover and characterize circulating tumour cells, alterations to the epigenome, identify changes in protein folding and splicing, and elucidate potential drug targets in clinical samples. By working with Cancer Registry , Clinical Trials Unit and the Manitoba Tumour Bank, we can conduct population studies to determine the prevalence of our findings in a larger patient population.

Brain Cancer

Spencer Gibson, PhD

In maintaining integrity and homeostasis of multicellular organisms, the balance between cell death and survival is fundamentally important. When this balance is altered, diseases such as cancer occur. One protein important in the regulation of cell death is BNIP3 which is induced under low oxygen (hypoxia) conditions and is over expressed in solid tumours. This paradox of BNIP3 killing cancer cells while being over expressed in live cells within tumours is a focus of our research. Three explanations could account for these differences and act as a mechanism for cancer progression.

Cell survival is as important as cell death. The epidermal growth factor receptor (EGFR) is expressed at high levels in several cancers including breast cancer. We discovered that pretreatment of breast cancer cell lines with epidermal growth factor (EGF) effectively blocked drug and death receptor induced apoptosis. This protection from apoptosis is mediated by a serine threonine kinase (AKT) through up-regulation of the Bcl-2 anti-apoptotic family member Mcl-1. Besides breast cancer, we have found that a lipid, lysophosphatic acid (LPA) blocks apoptosis in chronic lymphocytic leukemia (CLL) cells using a similar mechanism. We are currently investigating the regulatory elements controlling Mcl-1 expression.

The goal of my research is to define the signal transduction pathways leading to cell death or survival. This will elucidate targets that could tip balance in favour of cell death and will be the foundation to establish clinical trials using molecular targeted therapies to increase effectiveness of chemotherapy in cancer.

 

Contact Information:

5008b-675 McDermot Ave
Winnipeg, Mb
R3E 0V9
Phone: 204-787-2051
Email: Dr Spencer Gibson PhD 

PubMed Links

Dr Sachin Katyal, PhD

Modulating DNA Damage repair mechanisms to enhance brain tumour treatment success

DNA strand breaks occur on a daily basis in cells due to cell stress, environmental factors, oxidation and metabolism. Damaged DNA is resolved by dedicated DNA damage response (DDR) and repair mechanisms in order to preserve genomic integrity and cell function. The goal of conventional chemotherapeutic drugs and radiotherapy is to elicit DNA damage to overwhelm the tumour’s innate DDR and induce cell death. However, tumour cells have remarkable ability to respond to DNA damage, repair and adapt thus allowing survival and eventual drug resistance. It is predicted that >90% of all tumours incur at least one defect in the DNA damage response (DDR), thus tumour cell survival relies upon enhanced activity of other compensatory DNA repair pathways. The aggressive and deadly brain tumour, glioblastoma multiforme (GBM) shows a very high level of recurrence due to emergence of chemo/radio-resistant tumour cell populations; patients usually live about 1 yr from their date of diagnosis. We are identifying the “back-up” DNA repair pathways in these deadly brain tumours so that we can enhance the patients’ treatment success and their quality-of-life.

DNA repair pathways are guardians of the cellular genome.

Every individual human cell is estimated to incur tens of thousands of DNA strand breaks due to environmental stress, oxidation, metabolic function and DNA decay. To preserve genomic integrity, these breaks are resolved by dedicated DNA damage repair (DDR) pathways that ensure faithful transmission of genomes in dividing cells to ensure proper cell function and survival. There are two classes of DNA strand breaks, double-strand breaks (DSBs) and DNA single-strand breaks (SSBs), which are resolved by specific repair pathways, DSBR and SSBR. The inability to properly process and repair SSBs can interfere with the DNA replication and transcriptional machinery resulting in persistent SSBs, formation of the particularly genotoxic DNA double-stranded break (DSB) lesion and aberrant gene expression resulting in a variety of cellular pathology, including: senescence, cancer and apoptosis. It is known that the diverse mechanisms involving cell cycle regulation, DDR pathways, cellular metabolism, and cell death act in concert in response to DNA damage. As such, cellular life and death decisions are balanced by these mechanisms as defective DDR in proliferating cells, including neuroprogenitors, can lead to cancer, while defective neuronal DDR can lead to neurodegeneration.

Anti-tumorigenic agents overwhelm cellular DNA repair responses with lethal levels of genotoxicity.

The objective of common front-line radiation and chemotherapeutic strategies used in the treatment of brain tumours is to induce DNA breaks so as to overwhelm the cellular DNA repair machinery thus promoting genomic damage and tumour cell death. However, as the intrinsic cellular DNA repair process counteracts the therapeutic efficacy of this strategy, high radiation and drug doses are required which result in harmful neural and systemic side effects. My research seeks to identify ways to dysregulate cellular DNA repair pathways in tumours and improve therapeutic success. In this regard, DNA damage repair pathways are an ideal clinical target as we can specifically kill cancer cells by lowering the radio- and chemotherapeutic threshold of tumour cell genotoxicity by inhibiting redundant DNA repair pathways.

My research uses advanced molecular, biochemical and genetic techniques to gain insight into the biology of mammalian DNA strand break repair pathways. My goal is to identify ways to manipulate these pathways to develop novel treatment strategies in the clinical management of cancer. We are seeking a very highly motivated postdoctoral fellows (with a strong history of previous success) to join our team.

 

Contact information:

675 McDermot Ave
Winnipeg, Mb R3E 0V9
ph.: 204-787-2765, fax: 204-787-2190
Email: Dr Sachin Katyal PhD

PubMed Links

Dr. Thomas Klonisch, MD PhD

I am interested in understanding mechanisms tumor cells utilize to bypass anticancer treatment in patients and use this information to develop more effective anticancer therapies. This includes testing the efficacy of novel small molecules, evaluating synthetic lethal combinations, and the use of nanotherapeutic strategies. Although I utilize mice for this research, such animal models have limitations for some human cancers, in particular brain cancer. We are employing methods to isolate brain tumor cells directly from patients and have generated an extensive brain tumor cell resource. This invaluable resource allows my translational team to test therapeutic strategies and address important questions related to gliomagenesis, stem/ progenitor cell plasticity, cellular heterogeneity within human brain tumors, survival strategies, and mechanisms of tissue invasion and metastasis of adult brain tumors. In addition, we employ brain tumor cells and patient blood samples to identify potential protein biomarker signatures and monitor immunological responses in glioblastoma patients.

Two molecular systems of great interest to me are the membrane-anchored G protein coupled relaxin receptor system and the nuclear stem cell factor High Mobility Group A2 (HMGA2) in brain and breast cancer cells. My team established a role for the relaxin receptor RXFP1 in human glioblastoma and identified a novel ligand of RXFP1 in human brain tumors. Using our established resource of isolated human glioma cells from human patients, my team was able to show a novel mechanism by which this RXFP1 receptor system mediates chemoresistance  to temozolomide in patient brain tumor cells. My research on the chromatin-binding protein HMGA2 has revealed important roles of this stem cell factor in human patient glioblastoma cells. We showed that HMGA2 is a base excision repair (BER) enzyme and protects replication forks and telomeres. We also demonstrated that HMGA2 alters the activation state of the ATR-CHK1 DNA repair signaling which protects GB cells from apoptosis upon exposure to DNA alkylating agents like temozolomide. Currently, we study the interaction of HMGA2 with key proteins involved in cell survival and investigate proteins and pathways we identified as synthetic lethal with HMGA2. Collectively, our results suggest that the RXFP1 receptor system and HMGA2 exert novel protective mechanisms at different cellular levels which collectively result in enhanced chemoresistance in cancer cells. Our ongoing research addresses two main goals: (i) identify protein signatures from patient blood samples that can indicate the presence of glioblastoma and (ii) use sophisticated basic science strategies to inform the development of more efficacious treatment options for cancer patients.

 

Information:

Dr. Thomas Klonisch

Professor & Head
Dept. of Human Anatomy and Cell Science

Director of the Histomorphology and Ultrastructural Imaging Platform
Director of the Glioma Cell Resource
Depts. of Surgery, Medical Microbiology & Infectious Diseases

Adjunct Scientist, CancerCare Manitoba

Honorary Professor of Shantou University Medical College, Shantou, China

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

133-745 Bannatyne Avenue, Winnipeg, Manitoba, Canada, R3E 0J9
Phone: +1 204 789 3893
Fax: +1 204 789 3920
Email: thomas.klonisch@umanitoba.ca

Pubmed Links

Dr. Tamra Werbowetski-Ogilvie, PhD

Central nervous system (CNS) tumors are among the most prevalent forms of childhood cancers accounting for nearly 20% of all new cases (Canadian Cancer Society Statistics, 2015). Medulloblastoma (MB) is the most common malignant primary pediatric brain tumor and is currently divided into 4 distinct molecular subtypes.: WNT, SHH, Group 3 and Group 4. Extensive genetic, molecular and clinical heterogeneity between these subgroups has made it difficult to assess the functional relevance of genes to tumor progession. The Werbowetski-Ogilvie lab employs high throughput flow cytometry-based screening platforms to identify and subsequently characterize novel roles for cell surface markers in regulating diverse medulloblastoma phenotypes both in vitro and in vivo. Utilizing a wide variety of functional assays including measures of self-renewal, differentiation, invasion and proliferation in vitro as well as tumor growth in vivo using xenograft models, the lab is currently investigating the role of CD271, also known as p75 neurotrophin receptor (p75NTR) or nerve growth factor receptor (NGFR), in regulating stem cell properties of SHH variant medulloblastoma cells.

In addition, the lab utilizes neural derivatives from human embryonic stem cells (hESCs) as a model system to study the mechanisms contributing to pediatric brain tumorigenesis. Using this powerful cell resource as both a complement to and surrogate for existing cell lines and heterogeneous patient samples, the goal is to better understand how genes such as the transcription factor orthodenticle homeobox 2 (OTX2) regulate the balance between self-renewed and differentiation to either prevent or sustain oncogenic properties.

Contact Information:

University of Manitoba
611-745 Bannatyne Avenue, BMSB
Winnipeg, MB  R3E 0J9
Phone:  204.789.3431
Fax:       204.789.3900
Lab:       204.977.5687
Tamra.Ogilvie@umanitoba.ca

Pubmed Links

Dr. Marco Essig

Dr. Marshall Pitz

Dr. Lawrence Ryner

Dr Magimairajan Issai Vanan, MD, MPH, FAAP

Our lab’s main focus is in translational Neuro-Oncology with special emphasis on Radiation and Chemotherapy sensitization of pediatric brain tumors, developmental neurobiology as related to brain tumors and neuro therapeutics (BBB permeability / novel drug delivery methods).

Radiation is an integral part of the therapeutic armamentarium in Pediatric Neuro-Oncology. The therapeutic benefits of radiotherapy are, however, accompanied by late toxicity that severely affects quality of life in children. Our lab has identified several potential targets that mediate radiation and chemotherapy resistance in pediatric brain tumors. Validation of these targets using patient derived xenografts (PDX) in orthotopic murine brain tumor models will provide us with novel radio-sensitization drugs with larger therapeutic window; when used with current treatment protocols, this may lead to low dose therapeutic radiation and less long term side effects in survivors of childhood brain tumors.

The blood vessels that vascularize the central nervous system (CNS) possess unique properties, termed the blood–brain barrier (BBB), which allow these vessels to tightly regulate the movement of ions, molecules, and cells between the blood and the brain. However the same barrier also prevents chemotherapeutic drugs from reaching the tumor. The BBB is frequently intact in diffuse intrinsic pontine glioma (DIPG) and restricts the delivery of systemically administered conventional and biological therapies. In collaboration with Dr Miller we are working on chemical (HAV / Cyclic peptides) and biological (SHH and Wnt) methods of transient alteration of BBB permeability in orthotopic tumor models (DIPG). This transient increase in BBB permeability will help us increase the efficacy of current therapy and hopefully improve outcome in this devastating tumor.  

Contact information

Dr Babu Sajesh PhD.

ON5025a-675 McDermot Ave
Winnipeg, MB, R3E 0V9, Canada.
Ph: 204-787-4171

Pubmed Links

Breast Cancer

James Davie, PhD, FCAHS, FRSC

Dr. Jim Davie is a Professor in the Department of Biochemistry and Medical Genetics at the University of Manitoba, a Senior Scientist at the CancerCare Manitoba Research Institute, and Scientist at the Children’s Hospital Research Institute of Manitoba. He is the Secretary of the Canadian Society for Molecular Biosciences, a Fellow of the Canadian Academy of Health Sciences and the Royal Society of Canada, and a Tier 1 Canada Research Chair in Chromatin Dynamics.

Epigenetic is a term used to describe changes in gene expression that are stable between cell divisions. Chromatin modifying enzymes including lysine acetytransferases (KATs), histone deacetylases (HDACs), histone kinases, histone phosphatases, lysine/arginine methyltransferases, lysine/arginine demethylases, ATP-dependent chromatin remodeling complexes and DNA methyltransferases mediate chromatin remodeling and are components of a complex epigenetic network regulating gene expression during development, differentiation and disease. Multistep tumourigenesis is a progression of events resulting from alterations in the processing of the genetic information. These alterations result from stable genetic changes (mutations) in tumour suppressor genes and oncogenes (e.g. RAS) and potentially reversible epigenetic changes. DNA methylation and histone post-translational modifications (PTMs) are two epigenetic mechanisms that are altered in cancer cells.

Dr. Davie's research program has three research themes designed to understand the roles of epigenetic programming and nuclear structure in gene expression in normal and cancer cells:

  1. to characterize histone PTMs and chromatin modifying enzymes associated with transcribed chromatin in normal and cancer cells;
  2. to investigate the mechanisms by which signal transduction pathways control chromatin dynamics;
  3. to explore the organization of chromatin in the nucleus of normal and cancer cells.

 

Contact information:

Children’s Hospital Research Institute of MB
600A-715 McDermot Avenue, JBRC
Winnipeg, MB R3E 3P4 Canada
Tel:  204.975.7732
Fax: 204.977.5691
Lab: 204.789.3561
Jim.Davie@umanitoba.ca

PubMed Links

Spencer Gibson, PhD

In maintaining integrity and homeostasis of multicellular organisms, the balance between cell death and survival is fundamentally important. When this balance is altered, diseases such as cancer occur. One protein important in the regulation of cell death is BNIP3 which is induced under low oxygen (hypoxia) conditions and is over expressed in solid tumours. This paradox of BNIP3 killing cancer cells while being over expressed in live cells within tumours is a focus of our research. Three explanations could account for these differences and act as a mechanism for cancer progression.

Cell survival is as important as cell death. The epidermal growth factor receptor (EGFR) is expressed at high levels in several cancers including breast cancer. We discovered that pretreatment of breast cancer cell lines with epidermal growth factor (EGF) effectively blocked drug and death receptor induced apoptosis. This protection from apoptosis is mediated by a serine threonine kinase (AKT) through up-regulation of the Bcl-2 anti-apoptotic family member Mcl-1. Besides breast cancer, we have found that a lipid, lysophosphatic acid (LPA) blocks apoptosis in chronic lymphocytic leukemia (CLL) cells using a similar mechanism. We are currently investigating the regulatory elements controlling Mcl-1 expression.

The goal of my research is to define the signal transduction pathways leading to cell death or survival. This will elucidate targets that could tip balance in favour of cell death and will be the foundation to establish clinical trials using molecular targeted therapies to increase effectiveness of chemotherapy in cancer.

 

Contact Information:

5008b-675 McDermot Ave
Winnipeg, Mb
R3E 0V9
Phone: 204-787-2051
Email: Dr Spencer Gibson PhD 

PubMed Links

Dr Etienne Leygue, PhD

Designing therapies slowing down or inhibiting estrogen signaling in breast cells has already saved thousands of women. Unfortunately, resistance to a specific drug can occur in some patients and alternative treatments remain needed. It appears that a combination of drugs, targeting different critical points of estrogen signaling at different times, will provide a more efficient protection and overcome the potential resistance to a single drug.

My current research aims at defining the mechanisms of action of the protein SRAP (Steroid Receptor RNA Activator Protein), product of the SRA1 gene. Several groups have explored the function of the non-coding SRA transcripts produced by this gene and demonstrated its role in activating estrogen signaling. In contrast, little is known about the function of the protein encoded by the coding SRA messengers we identified 17 years ago. We have however found that SRAP expression could be used as a prognostic and predictive factors in specific patient subgroups. We have also recently shown that SRAP controls cancer cell motility, suggesting a potential role in the mechanisms underlying invasion and metastases formation.

We hypothesize that further characterizing SRA RNA/SRAP mechanism of action will provide new windows of opportunity to design innovative therapeutic or preventive strategies to fight breast cancer.

Contact information:

5029 - 675 McDermot Ave
Winnipeg, MB R3E 0V9
phone:(204) 787-2785
Lab: (204) 787-2844
Fax: (204) 787-2190
Email: Dr Etienne Leygue PhD

PubMed Links.

Dr. Davinder Jassal

Dr. Jassal’s research focuses on the complementary use of multimodality cardiovascular imaging in the non-invasive assessment of heart failure syndromes at St. Boniface Albrechtsen Research Centre.

FANTAM study (Flaxseed in the mitigation of anthracycline and trastuzumab mediated cardiotoxicity)

Although the multifaceted treatment approach including radiotherapy, surgical resection, and chemotherapy can lead to remission in breast cancer patients, these methods can lead to harmful cardiotoxic side effects. The introduction of two chemotherapeutic agents, Doxorubicin and Trastuzumab, has led to an increase in overall survival in breast cancer; however, despite their beneficial effects in reducing tumour proliferation, these two anti-cancer drugs are associated with an increased risk of cardiotoxicity in nearly 1 in 4 women receiving this anti-cancer treatmetnt. Therefore, there is a need to further characterize this damage and mitigate its effects on cardiac health. Approximately 30% of breast cancer patients consume flaxseed in the management of their underlying disease. In addition to its ability to reduce the risk of tumour progression, this nutraceutical agent has potent cardiovascular properties. The FANTAM study is currently evaluating the cardioprotective effects of flaxseed and/or is bioactive components against Doxorubicin and Trastuzumab induced cardiotoxicity.

RAS-ASICS study (Avastin and Sutent Induced Cardiotoxicity Study)

An increased understanding of the pathophysiology of colorectal and renal cancers has led to the development of targeted therapies, including Bevacizumab (BVZ) and Sunitinib (SNT). Despite the effectiveness of these anti-cancer agents, their use is associated with an increased risk of developing cardiotoxicity. Although heart failure medications including renin-angiotensin system (RAS) antagonists are commonly used after cardiac dysfunction is detected in the cancer setting, little is known on their prophylactic role in the prevention of BVZ and SNT mediated cardiac dysfunction. Our study is evaluating the cardioprotective effects of RAS inhibitors in the prevention of BVZ and SNT mediated cardiotoxicity.

Contact information:

Dr. Davinder S. Jassal
Rm. 4010, St. Boniface Hospital Research, 351 Tache, R2H 2A6
Lab Phone. (204) 237-2599
Lab Office. (204) 235-3056
Hospital Office. (204) 237-2023
Email. djassal@sbgh.mb.ca

Pubmed Links

 

Dr. Thomas Klonisch, MD PhD

I am interested in understanding mechanisms tumor cells utilize to bypass anticancer treatment in patients and use this information to develop more effective anticancer therapies. This includes testing the efficacy of novel small molecules, evaluating synthetic lethal combinations, and the use of nanotherapeutic strategies. Although I utilize mice for this research, such animal models have limitations for some human cancers, in particular brain cancer. We are employing methods to isolate brain tumor cells directly from patients and have generated an extensive brain tumor cell resource. This invaluable resource allows my translational team to test therapeutic strategies and address important questions related to gliomagenesis, stem/ progenitor cell plasticity, cellular heterogeneity within human brain tumors, survival strategies, and mechanisms of tissue invasion and metastasis of adult brain tumors. In addition, we employ brain tumor cells and patient blood samples to identify potential protein biomarker signatures and monitor immunological responses in glioblastoma patients.

Two molecular systems of great interest to me are the membrane-anchored G protein coupled relaxin receptor system and the nuclear stem cell factor High Mobility Group A2 (HMGA2) in brain and breast cancer cells. My team established a role for the relaxin receptor RXFP1 in human glioblastoma and identified a novel ligand of RXFP1 in human brain tumors. Using our established resource of isolated human glioma cells from human patients, my team was able to show a novel mechanism by which this RXFP1 receptor system mediates chemoresistance  to temozolomide in patient brain tumor cells. My research on the chromatin-binding protein HMGA2 has revealed important roles of this stem cell factor in human patient glioblastoma cells. We showed that HMGA2 is a base excision repair (BER) enzyme and protects replication forks and telomeres. We also demonstrated that HMGA2 alters the activation state of the ATR-CHK1 DNA repair signaling which protects GB cells from apoptosis upon exposure to DNA alkylating agents like temozolomide. Currently, we study the interaction of HMGA2 with key proteins involved in cell survival and investigate proteins and pathways we identified as synthetic lethal with HMGA2. Collectively, our results suggest that the RXFP1 receptor system and HMGA2 exert novel protective mechanisms at different cellular levels which collectively result in enhanced chemoresistance in cancer cells. Our ongoing research addresses two main goals: (i) identify protein signatures from patient blood samples that can indicate the presence of glioblastoma and (ii) use sophisticated basic science strategies to inform the development of more efficacious treatment options for cancer patients.

 

Information:

Dr. Thomas Klonisch

Professor & Head
Dept. of Human Anatomy and Cell Science

Director of the Histomorphology and Ultrastructural Imaging Platform
Director of the Glioma Cell Resource
Depts. of Surgery, Medical Microbiology & Infectious Diseases

Adjunct Scientist, CancerCare Manitoba

Honorary Professor of Shantou University Medical College, Shantou, China

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

133-745 Bannatyne Avenue, Winnipeg, Manitoba, Canada, R3E 0J9
Phone: +1 204 789 3893
Fax: +1 204 789 3920
Email: thomas.klonisch@umanitoba.ca

Pubmed Links

Dr. Julian Kim

Current Positions/Affiliations

Julian Kim is a radiation oncologist at CancerCare Manitoba, and an Assistant Professor of Radiology in the Rady Faculty of Health Sciences at the University of Manitoba.

Research Interests

  • Metabolomic profiling of Lung Cancer
  • Polygenic Risk Profiling for Breast Cancer Prevention
  • Androgen Deprivation Therapy for Prostate Cancer
  • High Precision Radiotherapy Treatment Delivery (Real Time Transponder Beacon Guided Radiotherapy for lung and breast cancer patients)

Current Research

Dr. Kim is leading a study assessing a technique to diagnose non-small cell lung cancer using blood samples in order to speed up the diagnosis and treatment of non-small cell lung cancer. The diagnostic tests currently used to identify specific types of lung cancer from tumour biopsies can often take a month or longer. Since lung cancer often presents at a late stage and can grow quickly, timely diagnosis is imperative in order to initiate treatment prior to the disease spreading in the body. Dr. Kim is using an artificial intelligence technique called machine learning to analyze blood samples from Manitoba lung cancer patients to search for metabolomic signatures or patterns that identify lung cancer, which would speed up diagnosis and allow treatment to begin sooner. This study is funded by the Canadian Institutes for Health Research and the CancerCare Manitoba Foundation.

Dr. Kim is also leading a Phase II randomized clinical trial (The PREMIUM Trial) testing a common diabetes medication (Metformin) that has the potential to reduce unwanted side effects  experienced by men with prostate cancer who are treated with androgen deprivation therapy (ADT) and radiotherapy. ADT causes many prostate cancer patients to gain weight, which can lead to elevated blood pressure, blood sugar, and cholesterol. Metabolic syndrome occurs when all of these conditions occur together. Metabolic syndrome increases the risk of heart disease, stroke, and diabetes, so this study has the potential to reduce these other health risks for men with prostate cancer. This study is funded by the CancerCare Manitoba Foundation and the Alberta Cancer Foundation.

Dr. Kim is also a co-principal investigator of a joint clinical study with the Mayo Clinic (The GENRE Study) which is examining the impact of a new genetic test that predicts a women’s risk of developing breast cancer. The study’s goal is to determine if women who learn they are at high risk of breast cancer are subsequently more inclined to take Tamoxifen and other drugs that reduce their risk of getting breast cancer.

Selected Publications

1)  Julian Kim, Charles Butts, Wilson Roa et al. Dose-escalated Hypofractionated Intensity-Modulated Radiation Therapy With Concurrent Chemotherapy For Inoperable or Unresectable Non-Small Cell Lung Cancer. American Journal of Clinical Oncology. Vol 40(3), June 2017.

 

2) Julian Kim, Faith Davis, Charles Butts, Marcy Winget. Waiting Time Intervals for Non-Small Cell Lung Cancer Diagnosis and Treatment in Alberta: Quantification of Intervals and Identification of Risk Factors Associated with Delays. Clinical Oncology. Vol 28 (16), Dec 2016.

 

3) Rene Razzak, Eric Bedard, Julian Kim, et al. MicroRNA expression profiling of sputum for the detection of early and locally advanced non-small cell lung cancer: a prospective case-control study. Current Oncology, Vol 23, No 2, April 2016.

 

4) Julian Kim, Sayf Gazala, Eric Bedard et al. Non-Small Cell Lung Cancer Detection Using MicroRNA Expression Profiling of Bronchoalveolar Lavage Fluids and Sputum. Anticancer Research. Vol 35, No 4, April 2015

 

5) Julian Kim, Roy Ma, et al. Long-Term Outcomes of Fractionated Stereotactic Radiotherapy (FSRT) For Pituitary Adenomas at the BC Cancer Agency (BCCA).  International Journal of Radiation, Biology, Physics, Vol 87, No 3, Nov 2013

Dr. Michael Mowat, PhD

One 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 tumour cells 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, integrates into genes and interferes with their function. After selection for drug resistant cells, the underlying genes disrupted by the virus are studied for their role in programmed cell death and drug resistance. By understanding the genetic basis of resistance to cell death, completely new treatments can be devised.

A gene that came out of these screens was the Dlc-2 (Deleted in liver cancer two) tumour suppressor gene. We are now studying the role this gene plays, along with the closely related Dlc-1 gene, in tumour cell progression and drug response. The Dlc-1 gene is found deleted in over 50 percent of breast, lung, liver and colon cancers. Also, the other normal copy of the gene is frequently silenced by promoter methylation. To study the role these genes play in the body, we have developed conditional knockout mouse models. With these mouse models, we can study the role the Dlc genes play in lung, and breast cancer spread through the body and anti-cancer drug response.

Contact information

5022-675 McDermot Ave
Winnipeg, Mb R3E 0V9
(204) 787-4139
Email: Dr Michael Mowat PhD

Pubmed links

Dr Leigh Murphy, PhD

Since estrogen is a major driver of human breast cancer, and the action of estrogen changes during breast tumourigenesis and breast cancer progression, the overall aim of my research program is to elucidate the mechanisms by which estrogen action changes during the development of breast cancer and how breast cancers develop resistance to endocrine therapies and progress from hormone dependence to independence. To do this my group is identifying the molecular players involved in the estrogen receptor signaling pathways in human breast tissues, how they are altered during tumourigenesis, and breast cancer progression to hormone independence.

We are specifically determining the types and putative function of estrogen receptor isoforms, i.e. estrogen receptor alpha and beta and its phosphorylated forms, that are expressed in human breast tissues in vivo, using tissues obtained from the Manitoba Breast Tumour Bank/Clinical Database. We have identified a phosphorylation profile of estrogen receptor alpha with prognostic significance. The kinases that are involved in regulating the estrogen receptor alpha phosphorylation score in vivo are now being studied as potential therapy targets. Estrogen and androgen signaling may have a role in some lung cancers so in collaboration with Drs Marshall Pitz, Shantanu Banerji, Sri Navaratnam and Gefei Qing, we are developing human lung cancer tissue microarrays and associated clinical information to explore the molecular players involved in the estrogen and androgen signaling pathways in lung tissue and relationship to clinical outcome.

In collaboration with Dr Peter Watson and the Manitoba Tumour Bank, we are also investigating tissue collection issues that may affect detection of various gene products in banked tissues.  Through the Manitoba Tumour Bank, we are contributing to genomic, proteomic  and metabolomic  cancer studies locally, nationally and internationally.

 

Contact information

Research Institute in Oncology and Hematology
6020-675 McDermot Ave
Winnipeg, Mb R3E 0V9
(204) 787-4071
Email: Dr Leigh Murphy PhD

Pubmed Links

Dr. Yvonne Myal, PhD

My long term research program is based on identifying breast/breast cancer specific biomarkers and understanding the biological role of these markers in the progression of breast cancer from a localized disease to metastases. Our research efforts over the last few years have been focused on two molecules, claudin 1, and the human prolactin inducible protein/gross cystic disease fluid protein, PIP/GCDFP-15.

PIP/GCDFP-15 is an established biomarker for abnormal breast function. PIP/GCDFP-15 is abundantly found in the fluid of benign cysts of the breast and its gene expression has been detected in more than 90% of breast cancers. Currently, its role in breast cancer as well as in normal breast development is presently not known. Our laboratory generated the first transgenic and knockout mouse models to address the function of this protein. Recent studies from our laboratory show that the role of the PIP/GCDFP-15 protein is multifunctional and may have an immunomodulatory role.

We are studying the role of the tight junction protein, claudin 1, in breast cancer progression and metastasis. Tight junction proteins are localized in the membrane of epithelial cells, including mammary epithelial cells, the milk secreting cells of the breast. Most breast cancers develop from this cell type. Tight junction proteins are important for cell-cell interactions, regulating the transport of ions and nutrients between these cells. The breakdown of cell-cell interaction and a loss of tight junction proteins have long been associated with the progression of several cancers. However, such an involvement of claudin 1 in breast cancer has not been delineated. We are focusing on in vitro and in vivo approaches to address this question, as well as examining relationships between claudin 1 expression and tumour aggressiveness and patient survival in human invasive breast cancer cohorts.

Contact information

University of Manitoba Department of Pathology
P228E Pathology Building
770 Bannatyne Ave Winnipeg, Mb R3E 0W3
(204) 787-3874
Email: Dr Yvonne Myal PhD

PubMed Links

Dr. Saroj Niraula

Dr. Stephen Pistorius, MSc (Med), PhD, PPhys, FCOMP

Dr. Stephen Pistorius is a Senior Scientist at the Research Institute for Oncology and Hematology (RIOH).  He serves as the Director of the Medical Physics Graduate Program and the Vice Director of the Biomedical Engineering Program at the University of Manitoba where he is a Professor of Physics and Astronomy and Associate Professor of Radiology. He served as the President (2006-2008) of the Canadian Organization of Medical Physics (COMP) and is currently the President of the Canadian Association of Physicists (CAP). He is a certified Medical Physicist, a licensed Professional Physicist (P.Phys.), a senior member of the IEEE, and a Fellow of the Canadian Organization of Medical Physics (FCOMP).

Prof. Pistorius is interested in improving, optimizing and quantifying various diagnostic and therapeutic techniques and in understanding the radiation transport of clinically useful imaging and treatment modalities. He supervises numerous graduate and undergraduate students carrying out research in cancer imaging, specifically, in developing improved systems for cancer diagnosis which use scatter enhanced x- and g-ray techniques and microwaves; as well as on-line megavoltage portal imaging, aimed at real time in-vivo tracking of motion and optimization of complex radiotherapy treatments and in the use of artificial intelligence to help analyze images and to detect and classify tumors. The author of over 200 publications and presentations, he has received over $4.5M in grant funding in the last 5 years, is a Fellow of COMP, and he and his students have received numerous national and international awards for their research.  Students interested in research in any of the above areas are welcome to contact him.

Contact Information:

Phone: 204.787.4134
Email: spistorius@cancercare.mb.ca
Website

Orcid Links

Pubmed Links

Dr. Marshall Pitz

Dr Afshin Raouf, PhD

It is becoming clear that progress in treating breast cancer effectively requires a better understanding of the cells that generate and maintain breast tumours (cancer stem cells) and how they are abnormal patients. Accumulating evidence suggests that breast cancer tumours are maintained by a rare subset of cells that have stem cell properties, indicating that new therapies are needed to eliminate them to achieve more effective treatments with decreased chance of tumour recurrence. This concept reinforces the hypothesis that normal stem and progenitor cells are important cellular targets in the initiation and recurrence of human breast cancer. Indeed, mutations arising in stem cells could represent an efficient process for hijacking the regulated proliferation and differentiation of primitive normal mammary cells.

My research program has 3 objectives:

  1. Identify primitive cell programs that regulate the normal function of the mammary stem and progenitor cells.
  2. Establish how the inappropriate execution of these programs causes the normal stem cells and progenitors to acquire a cancer stem cell phenotype.
  3. Determine whether this understanding can be leveraged to develop therapies against breast cancer stem cell populations.

Toward accomplishing this objective we have developed techniques to isolate highly purified populations of stem cells and distinct progenitors from breast tissue to examine the specific roles of breast oncogenes such as the NOTCH receptors and non-coding RNA such as H19 and Insulin-like growth factor binding protein 7 (IGFBP7) in regulating the biology and function of these rare cells in health and in disease (i.e. breast cancer).

 

Contact information

Basic Medical Science Building
613-745 Bannatyne Avenue
Winnipeg, MB, Canada
R3E 0J9
Contact numbers:
Office number 204-975-7704
Lab number 204-975-7703
Email: Dr Afshin Raouf PhD

Pubmed links

Dr. Anuraag Shrivastav

Dr Wayne Xu, PhD

My expertise is applying Bioinformatics approaches to solve biological problems, particularly to unveil the genomic and epigenomic regimes using large high throughput data. My current research themes are:

1.Discovering gene signatures and targets for precision medicine of cancer therapy

With the advancement in Next-Generation Sequencing (NGS) technology, multiple international consortia have made numerous large genomic and epigenomic data of various cancer types publicly accessible. Our lab develops new bioinformatics models and uses large datasets to discover new gene signatures and gene targets aiming to aid tailoring for patient therapies. Our lab also collaborates with molecular biology scientists and clinician-scientist to validate our discoveries using tumor tissue samples and translate them into clinical studies. 

2.Investigating tumorigenesis beyond driver gene mutations

It is generally accepted that driver gene mutations initialize the tumorigenesis. However, very few driver mutations are shared among cancers and even in the same patient with multiple tumors of the same types, there are few or none common drivers. Our lab collaborates on targeted, whole exome, and whole genome sequencing data. We investigate SNV, CNV, SV, INDEL, LOH, cellular clonal structure in order to uncover new tumorigenesis factors in lung cancer.

3.Developing new algorithms and tools for large sequencing data analysis

The next-generation sequencing (NGS) technologies have produced large amount of various genomic data for a variety of experiments which had a tremendous impact on life science research. RNA-seq uses the large amount of short sequence reads to interrogate the transcriptome, the existence and level of RNAs. How to accurately quantify the RNAs' level without much computational cost has been one of the focuses for NGS bioinformatics research. Our lab designs an alternative RNA-seq estimate method called Feature Structure (FEST) method. In contrast to current RNA-seq expression estimation methods that do not account for GC bias and RNA degradation, FEST will handle read redundant, GC bias probability, and degradation rate in each read to estimate the expression level.

Contact information

675 McDermot Ave
Winnipeg, MB, Canada R3E 0V9

Pubmed Links

Colorectal Cancer

Dr Kirk McManus, PhD

Genome instability is associated with virtually all cancer types, but the underlying gene defects and mutations causing genome instability are not well understood. Mutations that cause chromosome instability (CIN), or abnormal chromosome numbers, are now widely recognized as predisposing factors that drive cancer formation. In fact, mutations in CIN genes are associated with disease progression, the acquisition of drug resistance and poor patient survival. Nevertheless, and despite these associations, the mutated genes giving rise to CIN remain largely unknown. Thus, a fundamental goal of our research team is to identify and characterize new CIN genes, and to uncover their roles in cancer development. To achieve this goal, we routinely couple genetics, biochemistry, cell biology, molecular biology and high-content imaging microscopy to identify the mutated genes and abnormal pathways that drive colorectal and ovarian cancer formation.

The second major goal of our research team is to identify and develop novel therapeutic strategies to combat cancers, like colorectal, ovarian and breast. In this regard, we use genetics, cell biology and innovative microscopy approaches to screen and identify new drug targets and lead chemotherapeutics that specifically kill cancer cells with mutated CIN genes. A major benefit of this approach is that the therapeutic effects are better targeted towards cancer cells, and thus it is predicted to minimize and/or eliminate the adverse side effects associated with many current chemotherapeutics. This innovative cancer-specific targeting concept is referred to as synthetic lethality and is now beginning to show promise within the clinic.

Contact information

ON6010-675 McDermot Ave
Winnipeg, MB R3E 0V9
(204) 787-2833 (office)
(204) 787-2150 (lab)
Email: Dr Kirk McManus PhD
Visit my lab's website

 

PubMed Links

Dr. Harminder Singh

Dr. Harminder Singh is a clinician scientist, epidemiologist and practicing gastroenterologist. Dr. Singh received his MBBS and MD from All India Institute of Medical Sciences, internal medicine training at the Albert Einstein College of Medicine, New York and Masters in Public Health from the University of Manitoba. He received training in gastroenterology, gastrointestinal oncology and health outcomes research at University of Manitoba.

Dr. Singh is currently an Associate Professor of Medicine in the departments of Internal Medicine and Community Health Sciences at the University of Manitoba. He is a former member of the Canadian Task Force on Preventive Health Care, an organization developing and disseminating clinical practice guidelines for primary care, including for screening for cancers. He is co-leading the Manitoba Hereditary GI Cancer Clinic.

Dr. Singh’s research interests include prevention and screening for cancers, clinical epidemiology, pharmaco-epidemiology and health services research.  He is currently leading a large knowledge translation study to improve processes around colonoscopy, an essential test to diagnosis colorectal cancer.

Epidemiology and Health Services Research

Kathleen Decker, PhD

Dr Kathleen Decker is a Scientist in the Research Institute of Oncology and Hematology and an Assistant Professor in the Department of Community Health Sciences, Max Rady College of Medicine, Rady Faculty of Health Sciences at the University of Manitoba. She leads the Health Services Research Group in the Research Institute and works closely with the Department of Epidemiology and Cancer Registry at CancerCare Manitoba. Her research examines how and when Manitobans use health care across the cancer control continuum from screening to survivorship. The goal of her research and that of the Health Services Research Group is to investigate the reasons that contribute to the challenges that face cancer control (e.g., inequities in access, increasing costs, rising incidence) and generate new knowledge and evidence-based solutions to achieve better health outcomes, improve the health and quality of life of Manitobans diagnosed with cancer, and optimize health system performance and sustainability. She currently holds research grants from the Canadian Institutes of Health Research and the CancerCare Manitoba Foundation. She has a Ph.D. from the University of Manitoba, a MHA from Dalhousie University, and an Honours B.Sc. from the University of Waterloo.

PubMed Links

Dr. Harminder Singh

Dr. Harminder Singh is a clinician scientist, epidemiologist and practicing gastroenterologist. Dr. Singh received his MBBS and MD from All India Institute of Medical Sciences, internal medicine training at the Albert Einstein College of Medicine, New York and Masters in Public Health from the University of Manitoba. He received training in gastroenterology, gastrointestinal oncology and health outcomes research at University of Manitoba.

Dr. Singh is currently an Associate Professor of Medicine in the departments of Internal Medicine and Community Health Sciences at the University of Manitoba. He is a former member of the Canadian Task Force on Preventive Health Care, an organization developing and disseminating clinical practice guidelines for primary care, including for screening for cancers. He is co-leading the Manitoba Hereditary GI Cancer Clinic.

Dr. Singh’s research interests include prevention and screening for cancers, clinical epidemiology, pharmaco-epidemiology and health services research.  He is currently leading a large knowledge translation study to improve processes around colonoscopy, an essential test to diagnosis colorectal cancer.

Head & Neck

Dr Alok Pathak, MD

The core of Dr. Pathak’s research has been cancers of Head and Neck, particularly those of thyroid and oral cavity.  His research interests span both clinical and translational research (Int J Cancer 2016).  He has established a population based cohort of about 3100 thyroid cancer patients and has followed their oncological outcome of over 35,000 patient-years. His paper on the changing face of thyroid cancer (Cancer Medicine 2013) challenges the premise that the recent rise in thyroid cancer is  just due to the over diagnosis,  as the increase in age standardized incidence was not restricted to smaller thyroid cancers (micro-carcinomas). He questioned the appropriateness of the age threshold of 45 year in risk stratification of thyroid cancer (Endocrine Connections 2013, J Surg Oncol 2016) and proposed 55 year to be a better age cut off for TNM stage grouping (Eur J Surg Oncol 2015). This was followed by a multi-institutional study of around 9484 patients (Thyroid 2016) and subsequent change in the  8th edition of TNM staging for thyroid cancer. Dr. Pathak has developed nomograms for predicting the oncological outcome of thyroid cancer (JCEM 2013), compared it with other existing models (Eur J Surg Oncol 2016) and adapted it to a web based model for individualized oncological risk in thyroid cancer patients (www.survivalcurves.net). His recent papers on increased FDG uptake in Hürthle cell neoplasm highlights the confounding influence of Hürthle cells in causing false positivity on FDG- PET scans (Ann Med Surg 2016, Ann Nuc Med 2016)

 

Contact information

ON2048 - 675 McDermot Avenue
CancerCare Manitoba
Winnipeg Manitoba
Canada R3E 0V9
Phone: (204) 787-1340
Fax:(204) 787-2768

Pubmed Links

Leukemia and Malignant Blood Disorders

Dr. Versha Banerji

Dr. Versha Banerji is a Clinician Scientist at CancerCare Manitoba and Senior Scientist at the Research Institute in Oncology and Hematology. She is also a co-investigator on the Research Manitoba CLL Research Cluster.

Cancer cell metabolism is considered a hallmark of cancer development. Current treatment strategies are based on targeting DNA replication or signaling pathways to control cancer cell growth proliferation and survival. My laboratory firmly believes that targeting cancer cell metabolism is a novel approach in the fight against cancer.  My research program is focused on evaluating the metabolism power house, the mitochondria, by creating bioenergetics profiles of cancer cells. We then use the readouts to determine how new drugs can alter the profiles and identify doses that may be safer in patients and better tolerated by patients for treatment of their cancers. Although my work has mainly focused on Chronic Lymphocytic Leukemia, this work has broad applicability to any cancer type. This platform serves to supplement traditional drug screening for novel agents. We also use a variety of molecular biology techniques in the laboratory and genetic loss of targets as validation for drug screens.  We also investigate how cancer metabolism is linked with circadian rhythm. As a physician, I value the use of novel agents in clinical practice and how they affect my patients. Thus, my research program also evaluates the implementation of novel agents in clinical practice, the impact on treatment course of patients including side effects as well as the costs of new drug for health care delivery.

PubMed Links

Spencer Gibson, PhD

In maintaining integrity and homeostasis of multicellular organisms, the balance between cell death and survival is fundamentally important. When this balance is altered, diseases such as cancer occur. One protein important in the regulation of cell death is BNIP3 which is induced under low oxygen (hypoxia) conditions and is over expressed in solid tumours. This paradox of BNIP3 killing cancer cells while being over expressed in live cells within tumours is a focus of our research. Three explanations could account for these differences and act as a mechanism for cancer progression.

Cell survival is as important as cell death. The epidermal growth factor receptor (EGFR) is expressed at high levels in several cancers including breast cancer. We discovered that pretreatment of breast cancer cell lines with epidermal growth factor (EGF) effectively blocked drug and death receptor induced apoptosis. This protection from apoptosis is mediated by a serine threonine kinase (AKT) through up-regulation of the Bcl-2 anti-apoptotic family member Mcl-1. Besides breast cancer, we have found that a lipid, lysophosphatic acid (LPA) blocks apoptosis in chronic lymphocytic leukemia (CLL) cells using a similar mechanism. We are currently investigating the regulatory elements controlling Mcl-1 expression.

The goal of my research is to define the signal transduction pathways leading to cell death or survival. This will elucidate targets that could tip balance in favour of cell death and will be the foundation to establish clinical trials using molecular targeted therapies to increase effectiveness of chemotherapy in cancer.

 

Contact Information:

5008b-675 McDermot Ave
Winnipeg, Mb
R3E 0V9
Phone: 204-787-2051
Email: Dr Spencer Gibson PhD 

PubMed Links

Geoff Hicks, PhD

Transformation

Mutations (from the ES cell library) transmitted to the germline will focus on genes known or suspected to be involved in tumour progression. Understanding the normal function of a gene in mammalian development is a powerful approach to understanding how the oncogene contributes to the respective cancer. The focus of the lab is on genes which are translocated in the development of human cancers; specifically, the TLS and EWS genes. While the translocations and the associated cancers for these genes are highly characterized, little is known about function of the genes themselves or how they contribute to tumour development. Our approach is to analyze developmental defects in mice that are either deficient for specific gene (and are otherwise genetically identical to wild-type mice). For example TLS is a gene that is translocated in many human soft tissue sarcomas and myelogenous leukemia. Functional analysis of mice that are homozygous for the TLS/FUS mutation has revealed TLS plays a critical role in the normal development of blood cells and in maintaining genomic stability. Using this approach, we have now discovered the how changes in TLS during cancer specifically prevent its normal role to limit cell proliferation and correct mutations in other genes -- both of which are hallmarks of cancer itself.

Contact information:
Regenerative Medicine Program
669 Basic Med Sci Bldg
745 Bannatyne Avenue
University of Manitoba
Winnipeg, Mb R3E 0J9
Phone: (204) 318-5287
Lab: (204) 318-5289
Email: Dr Geoff Hicks PhD

PubMed Links

Dr James Johnston MB, BCh, FRCPC

My primary research interest is in chronic lymphocytic leukemia (CLL) and I am involved in a number of translational research programs related to this disease. These studies involve the epidemiology and basic science of CLL, in addition to clinical trials. To further these activities, we have developed the CLL Clinic at CancerCare Manitoba and the Manitoba CLL Tumour Bank, which is housed in the RIOH. Our epidemiological studies have demonstrated that the incidence of CLL is much higher than previously reported with elderly male patients having a particularly poor prognosis. Our ongoing laboratory studies are evaluating new therapies and prognostic markers in CLL and examining the effects of age and gender on the biology of this cancer.

Contact information:

Department of Medical Hematology and Oncology
2078-675 McDermot Ave
Winnipeg, Mb
R3E 0V9

PubMed Links

Dr Sachin Katyal, PhD

Modulating DNA Damage repair mechanisms to enhance brain tumour treatment success

DNA strand breaks occur on a daily basis in cells due to cell stress, environmental factors, oxidation and metabolism. Damaged DNA is resolved by dedicated DNA damage response (DDR) and repair mechanisms in order to preserve genomic integrity and cell function. The goal of conventional chemotherapeutic drugs and radiotherapy is to elicit DNA damage to overwhelm the tumour’s innate DDR and induce cell death. However, tumour cells have remarkable ability to respond to DNA damage, repair and adapt thus allowing survival and eventual drug resistance. It is predicted that >90% of all tumours incur at least one defect in the DNA damage response (DDR), thus tumour cell survival relies upon enhanced activity of other compensatory DNA repair pathways. The aggressive and deadly brain tumour, glioblastoma multiforme (GBM) shows a very high level of recurrence due to emergence of chemo/radio-resistant tumour cell populations; patients usually live about 1 yr from their date of diagnosis. We are identifying the “back-up” DNA repair pathways in these deadly brain tumours so that we can enhance the patients’ treatment success and their quality-of-life.

DNA repair pathways are guardians of the cellular genome.

Every individual human cell is estimated to incur tens of thousands of DNA strand breaks due to environmental stress, oxidation, metabolic function and DNA decay. To preserve genomic integrity, these breaks are resolved by dedicated DNA damage repair (DDR) pathways that ensure faithful transmission of genomes in dividing cells to ensure proper cell function and survival. There are two classes of DNA strand breaks, double-strand breaks (DSBs) and DNA single-strand breaks (SSBs), which are resolved by specific repair pathways, DSBR and SSBR. The inability to properly process and repair SSBs can interfere with the DNA replication and transcriptional machinery resulting in persistent SSBs, formation of the particularly genotoxic DNA double-stranded break (DSB) lesion and aberrant gene expression resulting in a variety of cellular pathology, including: senescence, cancer and apoptosis. It is known that the diverse mechanisms involving cell cycle regulation, DDR pathways, cellular metabolism, and cell death act in concert in response to DNA damage. As such, cellular life and death decisions are balanced by these mechanisms as defective DDR in proliferating cells, including neuroprogenitors, can lead to cancer, while defective neuronal DDR can lead to neurodegeneration.

Anti-tumorigenic agents overwhelm cellular DNA repair responses with lethal levels of genotoxicity.

The objective of common front-line radiation and chemotherapeutic strategies used in the treatment of brain tumours is to induce DNA breaks so as to overwhelm the cellular DNA repair machinery thus promoting genomic damage and tumour cell death. However, as the intrinsic cellular DNA repair process counteracts the therapeutic efficacy of this strategy, high radiation and drug doses are required which result in harmful neural and systemic side effects. My research seeks to identify ways to dysregulate cellular DNA repair pathways in tumours and improve therapeutic success. In this regard, DNA damage repair pathways are an ideal clinical target as we can specifically kill cancer cells by lowering the radio- and chemotherapeutic threshold of tumour cell genotoxicity by inhibiting redundant DNA repair pathways.

My research uses advanced molecular, biochemical and genetic techniques to gain insight into the biology of mammalian DNA strand break repair pathways. My goal is to identify ways to manipulate these pathways to develop novel treatment strategies in the clinical management of cancer. We are seeking a very highly motivated postdoctoral fellows (with a strong history of previous success) to join our team.

 

Contact information:

675 McDermot Ave
Winnipeg, Mb R3E 0V9
ph.: 204-787-2765, fax: 204-787-2190
Email: Dr Sachin Katyal PhD

PubMed Links

Dr. Rami Kotb

Dr. Sabine Mai

Dr. Mai was the first to show that the oncogene c-MYC drives the onset of genomic instability and nuclear genome remodeling, which she identified as a characteristic feature of cancer cells. This concept was recently recognized as a critical advance in molecular medicine and featured in the Cold Spring Harbour Perspectives in Medicine book “Myc and the pathways to cancer”. Dr. Mai was first to demonstrate telomere-dependent nuclear genome remodeling in cancer that serves as a mechanism of tumor initiation and progression, and also as a structural biomarker for cancer aggressiveness. To measure cancer genome remodeling, she applied quantitative 3D nuclear telomere imaging and analysis tools in translational research studies to multiple cancer sites including Hodgkin’s lymphoma and multiple myeloma. Her work showed that 3D nuclear telomere analysis is a powerful tool to stratify patients into distinct groups of stable and aggressive disease, which will, upon successful translation to the clinic, enable personalized cancer treatment decisions. This novel approach of 3D nuclear re-organization as a structural biomarker in cancer provides the first evidence that 3D nuclear telomere organization can be used as a hallmark of clinical decision-making.

Dr. Mai created the Genomic Centre for Cancer Research and Diagnosis (**GCCRD** link) at U Manitoba, a world-leading imaging facility with four grants from the Canada Foundation for Innovation (over $13M). The GCCRD features the first super resolution imaging facility in North America. Dr. Mai was first to study the 3D spatial organization of the cancer cell genome by super resolution microscopy, allowing for unprecedented insights into the cancer cell genome.

Over her career, Dr. Mai has trained over 1500 national and international students, postdoctoral fellows, scientists and clinicians, and has conducted advanced imaging courses in other countries including Thailand which helped in setting up 34 new imaging facilities there. Over the past 5 years, Dr. Mai has given 46 invited lectures, organized an international Imaging Symposium (2014), co-organized World Cancer 2016 in London (UK), and chaired sessions in this and other conferences. In 2015, Dr. Mai was recognized as one of the “Top 100, Canada’s Most Powerful Women” in the category of trailblazer and trendsetter to honor her engagement in research and training, and her work in translating her research from the bench to the bedside.

Contact information:

6046-675 McDermot Ave
Winnipeg, Mb R3E 0V9
(204) 787-2135
Email: Dr Sabine Mai PhD

PubMed Links

Kristjan Paulson, MD

Dr. Paulson’s interests are focused in the areas of clinical effectiveness and health services research in acute leukaemia and blood and marrow transplantation (BMT). He is the Scientific Director of the Canadian Blood and Marrow Transplant Group Registry, a prospectively collected database with detailed clinical data on over 10,000 Canadians who have undergone BMT.  He also is the Registry Lead for the Canadian National Transplant Research Program, a CIHR funded transplant research network, and has conducted multiple studies reviewing disparities in access to transplant and other complicated health services interventions.

Contact information

ON2078-675 McDermot Ave
Winnipeg, Mb
R3E0V9

Pubmed Links

Imaging and Medical Physics

Dr. Marco Essig

Dr. Boyd McCurdy

Dr. Stephen Pistorius, MSc (Med), PhD, PPhys, FCOMP

Dr. Stephen Pistorius is a Senior Scientist at the Research Institute for Oncology and Hematology (RIOH).  He serves as the Director of the Medical Physics Graduate Program and the Vice Director of the Biomedical Engineering Program at the University of Manitoba where he is a Professor of Physics and Astronomy and Associate Professor of Radiology. He served as the President (2006-2008) of the Canadian Organization of Medical Physics (COMP) and is currently the President of the Canadian Association of Physicists (CAP). He is a certified Medical Physicist, a licensed Professional Physicist (P.Phys.), a senior member of the IEEE, and a Fellow of the Canadian Organization of Medical Physics (FCOMP).

Prof. Pistorius is interested in improving, optimizing and quantifying various diagnostic and therapeutic techniques and in understanding the radiation transport of clinically useful imaging and treatment modalities. He supervises numerous graduate and undergraduate students carrying out research in cancer imaging, specifically, in developing improved systems for cancer diagnosis which use scatter enhanced x- and g-ray techniques and microwaves; as well as on-line megavoltage portal imaging, aimed at real time in-vivo tracking of motion and optimization of complex radiotherapy treatments and in the use of artificial intelligence to help analyze images and to detect and classify tumors. The author of over 200 publications and presentations, he has received over $4.5M in grant funding in the last 5 years, is a Fellow of COMP, and he and his students have received numerous national and international awards for their research.  Students interested in research in any of the above areas are welcome to contact him.

Contact Information:

Phone: 204.787.4134
Email: spistorius@cancercare.mb.ca
Website

Orcid Links

Pubmed Links

Non-malignant Blood Disorders

Dr. Sara Israels, MD FRCPC

Our platelet research laboratory studies basic mechanisms of platelet function and investigates patients with inherited platelet function abnormalities, in conjunction with the clinical Haemostasis Laboratory. Our projects include:

1) Studies of patients with inherited platelet function disorders, with a particular interest the ultrastructure of platelets as defined by electron microscopy.

2) Development of a national registry of patients with inherited platelet disorders, an opportunity to improve our understanding of these rare conditions, aid in their diagnosis, and evaluate treatment options.

3) Initiatives to standardize laboratory testing of platelet function and evaluate new methods for testing that will be clinically relevant.

4) Investigating the role of CD63, a member of the tetraspanin superfamily present on platelet dense granule and lysosomal granule membranes, and expressed on the platelet surface following activation, where it associates with the platelet integrin αIIbβ3, and with the contractile platelet cytoskeleton. It plays a role in platelet spreading on adhesive surfaces. Understanding the role of CD63 has implications beyond platelet function, as it, and similar molecules, may be involved in tumour cell migration and metastases.

Contact information:

Department of Pediatric Hematology and Oncology
675 McDermot Ave
Winnipeg, Mb
R3E 0V9

PubMed Links

Dr. Ryan Zarychanski MD MSc FRCPC

Dr. Ryan Zarychanski is an Assistant Professor and Clinician-Scientist at the University of Manitoba in the Department of Medicine, Sections of Critical Care and of Hematology/Medical Oncology. Following subspecialty fellowships Hematology and Critical Care Medicine, he obtained a Masters degree in Epidemiology and Community Medicine, and undertook a research fellowship at the University of Ottawa. Dr. Zarychanski’s research focuses on the hematologic aspects of critical illness. Major programs of research include evaluating efficacy and safety of heparin and IVIG in patients with septic shock. Recent research includes evaluating processes of care in massive transfusion and investigating blood products and blood conservation in the critically ill.

Dr. Zarychanski is the Director of Knowledge Synthesis at the Centre for Healthcare Innovation in Winnipeg, Manitoba and was awarded the Lyonel G. Israels Professorship in Hematology from the University of Manitoba in 2016 and the Canadian Institute of Health Research (CIHR) New Investigator Award in 2014.

Contact information

2056-675 McDermot Ave
Winnipeg, MB R3E 0V9

Pubmed Links

Ovarian Cancer

Dr Kirk McManus, PhD

Genome instability is associated with virtually all cancer types, but the underlying gene defects and mutations causing genome instability are not well understood. Mutations that cause chromosome instability (CIN), or abnormal chromosome numbers, are now widely recognized as predisposing factors that drive cancer formation. In fact, mutations in CIN genes are associated with disease progression, the acquisition of drug resistance and poor patient survival. Nevertheless, and despite these associations, the mutated genes giving rise to CIN remain largely unknown. Thus, a fundamental goal of our research team is to identify and characterize new CIN genes, and to uncover their roles in cancer development. To achieve this goal, we routinely couple genetics, biochemistry, cell biology, molecular biology and high-content imaging microscopy to identify the mutated genes and abnormal pathways that drive colorectal and ovarian cancer formation.

The second major goal of our research team is to identify and develop novel therapeutic strategies to combat cancers, like colorectal, ovarian and breast. In this regard, we use genetics, cell biology and innovative microscopy approaches to screen and identify new drug targets and lead chemotherapeutics that specifically kill cancer cells with mutated CIN genes. A major benefit of this approach is that the therapeutic effects are better targeted towards cancer cells, and thus it is predicted to minimize and/or eliminate the adverse side effects associated with many current chemotherapeutics. This innovative cancer-specific targeting concept is referred to as synthetic lethality and is now beginning to show promise within the clinic.

Contact information

ON6010-675 McDermot Ave
Winnipeg, MB R3E 0V9
(204) 787-2833 (office)
(204) 787-2150 (lab)
Email: Dr Kirk McManus PhD
Visit my lab's website

 

PubMed Links

Dr. Michael Mowat, PhD

One 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 tumour cells 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, integrates into genes and interferes with their function. After selection for drug resistant cells, the underlying genes disrupted by the virus are studied for their role in programmed cell death and drug resistance. By understanding the genetic basis of resistance to cell death, completely new treatments can be devised.

A gene that came out of these screens was the Dlc-2 (Deleted in liver cancer two) tumour suppressor gene. We are now studying the role this gene plays, along with the closely related Dlc-1 gene, in tumour cell progression and drug response. The Dlc-1 gene is found deleted in over 50 percent of breast, lung, liver and colon cancers. Also, the other normal copy of the gene is frequently silenced by promoter methylation. To study the role these genes play in the body, we have developed conditional knockout mouse models. With these mouse models, we can study the role the Dlc genes play in lung, and breast cancer spread through the body and anti-cancer drug response.

Contact information

5022-675 McDermot Ave
Winnipeg, Mb R3E 0V9
(204) 787-4139
Email: Dr Michael Mowat PhD

Pubmed links

Dr Mark Nachtigal, PhD

Human epithelial ovarian cancer (EOC) is the fifth leading cause of death by cancer amongst women. Approximately 95 women in Manitoba will be diagnosed with EOC this year. If detected at early stages of the disease, the cure rate approaches 90%; however, >70% of women are diagnosed with advanced disease when rates of survival are closer to 30%. Even after initial successful responses to therapy, EOC recurs in ~85% of patients. My laboratory uses a combination of cellular and molecular approaches to investigate human EOC biology with a special interest in recurrent, chemotherapy-resistant disease. With the formation of the Manitoba Ovarian Biobanking Program (MOBP) and cooperation with national programs such as the Canadian Ovarian Cancer Research Consortium (COCRC), his lab will be able to more readily translate data obtained with EOC patient samples to clinically relevant results. The ability to isolate and use patient donated EOC cells in 3-dimensional primary culture provides a more relevant model to assess cell responses. In particular, he and his staff and trainees, in collaboration with other University of Manitoba scientists in RIOH and the Regenerative Medicine Program, are focusing on investigating aspects of EOC cell biology and chromosomal instability, in addition to evaluating novel lipid-based therapeutics for treatment of chemoresistant EOC. This laboratory-based research is being complemented by epidemiologic studies with colleagues in Gynecologic Oncology and the Department of Epidemiology at CCMB to evaluate whether recent changes in clinical management have produced positive outcomes for the EOC population in Manitoba. 

 

Contact information

Rm 333 Basic Medical Sciences Bldg.
745 Bannatyne Avenue
Winnipeg, Manitoba
Canada R3E 0J9
Tel. (204) 789 3708 (office)
Tel. (204 272 3174 (laboratory)
Fax (204) 789 3900
Email: Dr Mark Nachtigal PhD

Pubmed Links

Palliative Care and Psycho-Social Oncology

Harvey Max Chochinov, MD, PhD, FRCPC

Dr. Chochinov is a Distinguished Professor of Psychiatry at the University of Manitoba and Director of the Manitoba Palliative Care Research Unit, CancerCare Manitoba. His seminal publications addressing psychosocial dimensions of palliation have helped define core-competencies and standards of end-of-life care. He holds the only Canada Research Chair in Palliative Care and is a member of the Governing Council of the Canadian Institutes of Health Research. He also chairs the CIHR’s Standing Committee on Ethics. He did his undergraduate medical training and Psychiatric Residency at the University of Manitoba and completed a Fellowship in Psychiatric Oncology at Memorial Sloan-Kettering Cancer Center, New York, New York. In 1998, he completed a PhD in the Faculty of Community Health Sciences, University of Manitoba.

Dr. Chochinov has been doing palliative care research since 1990 with funding support from local, provincial and national granting agencies. He is a grantee of the Canadian Institutes of Health Research, the National Cancer Institute of Canada and the National Institute of Health. His work has explored various psychiatric dimensions of palliative medicine, such as depression, desire for death, will to live and dignity at the end of life.

Pubmed Links

Dr. Thomas Hack

Dr. Hack’s research interests include coping and adjustment to life-threatening cancer, and knowledge translation (KT). He has conducted the largest trials worldwide examining the utility and effectiveness of providing cancer patients with audio-recordings of primary treatment consultations, and has applied his KT expertise to assist CancerCare Manitoba in launching a consultation recording service as standard clinical practice.  He recently completed a study examining the use of consultation recordings in patients with brain tumor.  Dr. Hack is the Manitoba lead on CIHR study examining the implementation of a national online course to enhance oncology nurse therapeutic effectiveness in responding to cancer patient pain, fatigue, anxiety and depression. Dr. Hack is a member of KT Canada, and is collaborating on KT research projects with the Manitoba Palliative Care Research Unit and with colleagues in the UK and Australia.

CR3018, 369 Taché Ave, Winnipeg MB Canada R2H 2A6
Tel: (204) 235-3791
Fax: (204) 233-7214
thack@sbrc.ca or tom.hack@umanitoba.ca

Dr. Susan McClement RN, PhD

Dr. McClement is a Professor in the College of Nursing, Rady Faculty of Health Sciences, and holds specialty certification in Hospice and Palliative Nursing from the Canadian Nurses Association. She has been the recipient of awards for teaching excellence in undergraduate and graduate education at the University of Manitoba. Dr. McClement’s research interests in palliative and end-of-life care include the psychosocial dimensions of cancer anorexia cachexia syndrome, understanding the salient indicators of compassion in the provision of palliative care, the nature of expert nursing practice in care of the dying in a variety of health care contexts, ethical issues in the provision of palliative home care, and the development and evaluation of palliative care educational approaches. Dr. McClement’s work has been funded by the Manitoba Medical Services Foundation, Research Manitoba, the Canadian Institutes of Health Research, and the former National Cancer Institute of Canada.

Contact Information

Dr. Susan McClement
Office 475-Helen Glass Centre for Nursing
89 Curry Place University of Manitoba,
Winnipeg, Manitoba, R3E 2N2
Tele: (204) 474-9515
Email: susan.mcclement@umanitoba.ca

Pubmed Links

Pediatric

Dr. Sara Israels, MD FRCPC

Our platelet research laboratory studies basic mechanisms of platelet function and investigates patients with inherited platelet function abnormalities, in conjunction with the clinical Haemostasis Laboratory. Our projects include:

1) Studies of patients with inherited platelet function disorders, with a particular interest the ultrastructure of platelets as defined by electron microscopy.

2) Development of a national registry of patients with inherited platelet disorders, an opportunity to improve our understanding of these rare conditions, aid in their diagnosis, and evaluate treatment options.

3) Initiatives to standardize laboratory testing of platelet function and evaluate new methods for testing that will be clinically relevant.

4) Investigating the role of CD63, a member of the tetraspanin superfamily present on platelet dense granule and lysosomal granule membranes, and expressed on the platelet surface following activation, where it associates with the platelet integrin αIIbβ3, and with the contractile platelet cytoskeleton. It plays a role in platelet spreading on adhesive surfaces. Understanding the role of CD63 has implications beyond platelet function, as it, and similar molecules, may be involved in tumour cell migration and metastases.

Contact information:

Department of Pediatric Hematology and Oncology
675 McDermot Ave
Winnipeg, Mb
R3E 0V9

PubMed Links

Dr Magimairajan Issai Vanan, MD, MPH, FAAP

Our lab’s main focus is in translational Neuro-Oncology with special emphasis on Radiation and Chemotherapy sensitization of pediatric brain tumors, developmental neurobiology as related to brain tumors and neuro therapeutics (BBB permeability / novel drug delivery methods).

Radiation is an integral part of the therapeutic armamentarium in Pediatric Neuro-Oncology. The therapeutic benefits of radiotherapy are, however, accompanied by late toxicity that severely affects quality of life in children. Our lab has identified several potential targets that mediate radiation and chemotherapy resistance in pediatric brain tumors. Validation of these targets using patient derived xenografts (PDX) in orthotopic murine brain tumor models will provide us with novel radio-sensitization drugs with larger therapeutic window; when used with current treatment protocols, this may lead to low dose therapeutic radiation and less long term side effects in survivors of childhood brain tumors.

The blood vessels that vascularize the central nervous system (CNS) possess unique properties, termed the blood–brain barrier (BBB), which allow these vessels to tightly regulate the movement of ions, molecules, and cells between the blood and the brain. However the same barrier also prevents chemotherapeutic drugs from reaching the tumor. The BBB is frequently intact in diffuse intrinsic pontine glioma (DIPG) and restricts the delivery of systemically administered conventional and biological therapies. In collaboration with Dr Miller we are working on chemical (HAV / Cyclic peptides) and biological (SHH and Wnt) methods of transient alteration of BBB permeability in orthotopic tumor models (DIPG). This transient increase in BBB permeability will help us increase the efficacy of current therapy and hopefully improve outcome in this devastating tumor.  

Contact information

Dr Babu Sajesh PhD.

ON5025a-675 McDermot Ave
Winnipeg, MB, R3E 0V9, Canada.
Ph: 204-787-4171

Pubmed Links

Prostate Cancer

Dr. Julian Kim

Current Positions/Affiliations

Julian Kim is a radiation oncologist at CancerCare Manitoba, and an Assistant Professor of Radiology in the Rady Faculty of Health Sciences at the University of Manitoba.

Research Interests

  • Metabolomic profiling of Lung Cancer
  • Polygenic Risk Profiling for Breast Cancer Prevention
  • Androgen Deprivation Therapy for Prostate Cancer
  • High Precision Radiotherapy Treatment Delivery (Real Time Transponder Beacon Guided Radiotherapy for lung and breast cancer patients)

Current Research

Dr. Kim is leading a study assessing a technique to diagnose non-small cell lung cancer using blood samples in order to speed up the diagnosis and treatment of non-small cell lung cancer. The diagnostic tests currently used to identify specific types of lung cancer from tumour biopsies can often take a month or longer. Since lung cancer often presents at a late stage and can grow quickly, timely diagnosis is imperative in order to initiate treatment prior to the disease spreading in the body. Dr. Kim is using an artificial intelligence technique called machine learning to analyze blood samples from Manitoba lung cancer patients to search for metabolomic signatures or patterns that identify lung cancer, which would speed up diagnosis and allow treatment to begin sooner. This study is funded by the Canadian Institutes for Health Research and the CancerCare Manitoba Foundation.

Dr. Kim is also leading a Phase II randomized clinical trial (The PREMIUM Trial) testing a common diabetes medication (Metformin) that has the potential to reduce unwanted side effects  experienced by men with prostate cancer who are treated with androgen deprivation therapy (ADT) and radiotherapy. ADT causes many prostate cancer patients to gain weight, which can lead to elevated blood pressure, blood sugar, and cholesterol. Metabolic syndrome occurs when all of these conditions occur together. Metabolic syndrome increases the risk of heart disease, stroke, and diabetes, so this study has the potential to reduce these other health risks for men with prostate cancer. This study is funded by the CancerCare Manitoba Foundation and the Alberta Cancer Foundation.

Dr. Kim is also a co-principal investigator of a joint clinical study with the Mayo Clinic (The GENRE Study) which is examining the impact of a new genetic test that predicts a women’s risk of developing breast cancer. The study’s goal is to determine if women who learn they are at high risk of breast cancer are subsequently more inclined to take Tamoxifen and other drugs that reduce their risk of getting breast cancer.

Selected Publications

1)  Julian Kim, Charles Butts, Wilson Roa et al. Dose-escalated Hypofractionated Intensity-Modulated Radiation Therapy With Concurrent Chemotherapy For Inoperable or Unresectable Non-Small Cell Lung Cancer. American Journal of Clinical Oncology. Vol 40(3), June 2017.

 

2) Julian Kim, Faith Davis, Charles Butts, Marcy Winget. Waiting Time Intervals for Non-Small Cell Lung Cancer Diagnosis and Treatment in Alberta: Quantification of Intervals and Identification of Risk Factors Associated with Delays. Clinical Oncology. Vol 28 (16), Dec 2016.

 

3) Rene Razzak, Eric Bedard, Julian Kim, et al. MicroRNA expression profiling of sputum for the detection of early and locally advanced non-small cell lung cancer: a prospective case-control study. Current Oncology, Vol 23, No 2, April 2016.

 

4) Julian Kim, Sayf Gazala, Eric Bedard et al. Non-Small Cell Lung Cancer Detection Using MicroRNA Expression Profiling of Bronchoalveolar Lavage Fluids and Sputum. Anticancer Research. Vol 35, No 4, April 2015

 

5) Julian Kim, Roy Ma, et al. Long-Term Outcomes of Fractionated Stereotactic Radiotherapy (FSRT) For Pituitary Adenomas at the BC Cancer Agency (BCCA).  International Journal of Radiation, Biology, Physics, Vol 87, No 3, Nov 2013

Dr. Sabine Mai

Dr. Mai was the first to show that the oncogene c-MYC drives the onset of genomic instability and nuclear genome remodeling, which she identified as a characteristic feature of cancer cells. This concept was recently recognized as a critical advance in molecular medicine and featured in the Cold Spring Harbour Perspectives in Medicine book “Myc and the pathways to cancer”. Dr. Mai was first to demonstrate telomere-dependent nuclear genome remodeling in cancer that serves as a mechanism of tumor initiation and progression, and also as a structural biomarker for cancer aggressiveness. To measure cancer genome remodeling, she applied quantitative 3D nuclear telomere imaging and analysis tools in translational research studies to multiple cancer sites including Hodgkin’s lymphoma and multiple myeloma. Her work showed that 3D nuclear telomere analysis is a powerful tool to stratify patients into distinct groups of stable and aggressive disease, which will, upon successful translation to the clinic, enable personalized cancer treatment decisions. This novel approach of 3D nuclear re-organization as a structural biomarker in cancer provides the first evidence that 3D nuclear telomere organization can be used as a hallmark of clinical decision-making.

Dr. Mai created the Genomic Centre for Cancer Research and Diagnosis (**GCCRD** link) at U Manitoba, a world-leading imaging facility with four grants from the Canada Foundation for Innovation (over $13M). The GCCRD features the first super resolution imaging facility in North America. Dr. Mai was first to study the 3D spatial organization of the cancer cell genome by super resolution microscopy, allowing for unprecedented insights into the cancer cell genome.

Over her career, Dr. Mai has trained over 1500 national and international students, postdoctoral fellows, scientists and clinicians, and has conducted advanced imaging courses in other countries including Thailand which helped in setting up 34 new imaging facilities there. Over the past 5 years, Dr. Mai has given 46 invited lectures, organized an international Imaging Symposium (2014), co-organized World Cancer 2016 in London (UK), and chaired sessions in this and other conferences. In 2015, Dr. Mai was recognized as one of the “Top 100, Canada’s Most Powerful Women” in the category of trailblazer and trendsetter to honor her engagement in research and training, and her work in translating her research from the bench to the bedside.

Contact information:

6046-675 McDermot Ave
Winnipeg, Mb R3E 0V9
(204) 787-2135
Email: Dr Sabine Mai PhD

PubMed Links

Thoracic (Lung, GI)

Dr. Shantanu Banerji

Structural changes or mutations in cancer genes have been identified as one of the causes of cancer. Common examples include gene amplification of the ERBB2 gene in 30% of breast cancers, EGFR gene mutations in 10% of North American lung cancer cases, and KIT mutations in occurring in over 70% of cases of a particular sarcoma subtype known as gastrointestinal stromal cancer. These mutations are particularly significant because they have led to the development of 'targeted' therapies, where a drug is designed to stop the growth of cancer cells with the specific gene abnormality, while sparing normal cells. This leads to therapy that not only prolongs survival, but reduces the toxicity of therapy.

The goal of my laboratory is to identify new gene targets in cancer using next generation DNA sequencing technology. We aim to characterize the rates of specific cancer associated mutations in the Manitoba population using resources like breast and lung cancer from the Manitoba Tumour Bank. We also analyze cancer tissue obtained from patients being treated at CancerCare Manitoba to try and identify targeted therapies that may be more effective for their cancer treatment. This is essential as we move towards more personalized therapy for all patients with cancer.

PubMed Links

Dr. David Dawe

Dr. Biniam Kidane

Dr. Julian Kim

Current Positions/Affiliations

Julian Kim is a radiation oncologist at CancerCare Manitoba, and an Assistant Professor of Radiology in the Rady Faculty of Health Sciences at the University of Manitoba.

Research Interests

  • Metabolomic profiling of Lung Cancer
  • Polygenic Risk Profiling for Breast Cancer Prevention
  • Androgen Deprivation Therapy for Prostate Cancer
  • High Precision Radiotherapy Treatment Delivery (Real Time Transponder Beacon Guided Radiotherapy for lung and breast cancer patients)

Current Research

Dr. Kim is leading a study assessing a technique to diagnose non-small cell lung cancer using blood samples in order to speed up the diagnosis and treatment of non-small cell lung cancer. The diagnostic tests currently used to identify specific types of lung cancer from tumour biopsies can often take a month or longer. Since lung cancer often presents at a late stage and can grow quickly, timely diagnosis is imperative in order to initiate treatment prior to the disease spreading in the body. Dr. Kim is using an artificial intelligence technique called machine learning to analyze blood samples from Manitoba lung cancer patients to search for metabolomic signatures or patterns that identify lung cancer, which would speed up diagnosis and allow treatment to begin sooner. This study is funded by the Canadian Institutes for Health Research and the CancerCare Manitoba Foundation.

Dr. Kim is also leading a Phase II randomized clinical trial (The PREMIUM Trial) testing a common diabetes medication (Metformin) that has the potential to reduce unwanted side effects  experienced by men with prostate cancer who are treated with androgen deprivation therapy (ADT) and radiotherapy. ADT causes many prostate cancer patients to gain weight, which can lead to elevated blood pressure, blood sugar, and cholesterol. Metabolic syndrome occurs when all of these conditions occur together. Metabolic syndrome increases the risk of heart disease, stroke, and diabetes, so this study has the potential to reduce these other health risks for men with prostate cancer. This study is funded by the CancerCare Manitoba Foundation and the Alberta Cancer Foundation.

Dr. Kim is also a co-principal investigator of a joint clinical study with the Mayo Clinic (The GENRE Study) which is examining the impact of a new genetic test that predicts a women’s risk of developing breast cancer. The study’s goal is to determine if women who learn they are at high risk of breast cancer are subsequently more inclined to take Tamoxifen and other drugs that reduce their risk of getting breast cancer.

Selected Publications

1)  Julian Kim, Charles Butts, Wilson Roa et al. Dose-escalated Hypofractionated Intensity-Modulated Radiation Therapy With Concurrent Chemotherapy For Inoperable or Unresectable Non-Small Cell Lung Cancer. American Journal of Clinical Oncology. Vol 40(3), June 2017.

 

2) Julian Kim, Faith Davis, Charles Butts, Marcy Winget. Waiting Time Intervals for Non-Small Cell Lung Cancer Diagnosis and Treatment in Alberta: Quantification of Intervals and Identification of Risk Factors Associated with Delays. Clinical Oncology. Vol 28 (16), Dec 2016.

 

3) Rene Razzak, Eric Bedard, Julian Kim, et al. MicroRNA expression profiling of sputum for the detection of early and locally advanced non-small cell lung cancer: a prospective case-control study. Current Oncology, Vol 23, No 2, April 2016.

 

4) Julian Kim, Sayf Gazala, Eric Bedard et al. Non-Small Cell Lung Cancer Detection Using MicroRNA Expression Profiling of Bronchoalveolar Lavage Fluids and Sputum. Anticancer Research. Vol 35, No 4, April 2015

 

5) Julian Kim, Roy Ma, et al. Long-Term Outcomes of Fractionated Stereotactic Radiotherapy (FSRT) For Pituitary Adenomas at the BC Cancer Agency (BCCA).  International Journal of Radiation, Biology, Physics, Vol 87, No 3, Nov 2013

We are always interested in pursuing collaborations with new partners. The Research Office assists all CancerCare Manitoba researchers by identifying new funding opportunities, provide awareness of deadlines, co-ordinate the annual CancerCare Manitoba Foundation grant competition, and support collaborative research opportunities to strengthen research teams. By fostering relationships with other researchers interested in working with RIOH and matching the team's research goals to funding opportunities, the Research Office develops strategies to increase research, training and funding opportunities.

The Research Officers are Dr Eilean McKenzie-Matwiy, Gary Annable and Dr. Mary-Ann Lindsay. Their responsibilities include facilitating grant applications, developing research collaborations, creating awareness of research opportunities, promoting research success, and organizing research events like CancerCare Manitoba Research Day. To contact either Research officers, please email.

Ashley Sitarz
Administrative Assistant to Dr. Spencer Gibson and Dr. Marshall Pitz
204-787-4983
Research Office ON4005 - 675 McDermot Ave

Chen Chen
Research Resource Impact Committee Co-ordinator
204-787-4170
Research Office ON5008 - 675 McDermot Ave

Wendy Bencharski
Administrative Assistant
204-787-2137
Research Office ON5008 - 675 McDermot Ave

Shauna Ceslak
Grant Accountant - Finance, Grant Administration
204-787-2112

Debbie Patkau
Administrative Assistant - Payroll, University appointments
204-787-4012

Cheryl Clague
Administrative Assistant
204-787-4925
Research Office ON4005 - 675 McDermot Ave

Dr. Mary-Ann Lindsay
204-787-4935