med ii summer research program 2018 supervisor … · awake craniotomies under 3-tesla ......
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Project Title Department Telephone Email
Impact of Online Resources and Social Media on Breast
Cancer Patients: A Survey-Based Research StudyDanielle Desautels
Internal
MedicineDanielle Desautels 204-787-1815 [email protected]
EHealth strategies to prevent hospital
admission/readmission in patients with advanced
chronic diseases: a systematic review
Paul Komenda
Internal
Medicine/
Nephrology
Michelle Di Nella 204-299-7359 [email protected]
Employment in patients with recent onset inflammatory
arthritis: prevalence and impact of clinical and
sociodemographic variables on work impairment at
diagnosis and over time.
Carol HitchonInternal
MedicineLily Lim 204-787-2020 [email protected]
Improving communication for colonoscopy Harminder SinghInternal
MedicineHarminder Singh 204-480-1311 [email protected]
Exploring the effects of peas on post-prandial glycaemic
and satiety responses using a metabolomics approachMichel Aliani
Human
Nutritional
Sciences and
Physiology
Michel Aliani 235-3048 [email protected]
Characterizing the molecular mechanisms of Ebola virus
persistence and cell tropism at the blood-testis barrier.Jason Kindrachuk
Medical
Microbiology &
Infectious
Diseases
Jason Kindrachuk 204-789-3807 [email protected]
Development and evaluation of new therapeutic
targets for multiple sclerosisSoheila Karimi
Physiology and
Pathophysiolog
y
Soheila Karimi 204-272-3109 [email protected]
Laparotomy or peritoneal drainage for the
management of surgical necrotizing enterocolitis and
spontaneous intestinal perforation
Anna Shawyer Surgery Salima Mukhi 204-787-4203 [email protected]
Awake craniotomies under 3-Tesla Intraoperative
Magnetic Resonance Imaging: A Descriptive Study and
Our Institutional Experience
Tumul ChowdhuryDepartment of
AnesthesiaTumul Chowdhury 2042985912 [email protected]
Investigating the Neuroprotective Role of Neuregulin-1
in Traumatic Spinal Cord InjurySoheila Karimi
Physiology
and Pathophysiology
Soheila Karimi 204-272-3109 [email protected]
Investigating Potential Bio-Markers for FASD Mojgan Rastegar
Biochemistry &
Medical
Genetics
Mojgan Rastegar 204-272-3108 [email protected]
Epigenetic control of gene regulatory network of neural
stem cellsMojgan Rastegar
Biochemistry &
Medical
Genetics
Mojgan Rastegar 204-272-3108 [email protected]
Targeting Cell Signaling by FDA-Approved Drugs in
Medulloblastoma Brain TumorMojgan Rastegar
Biochemistry &
Medical
Genetics
Mojgan Rastegar 204-272-3108 [email protected]
Defining Penicillin Allergy Documentation in Canadian
Primary Care PracticesAlexander Singer
Family
MedicineAlexander Singer 2042372885 [email protected]
Supervisor First
and Last Name
Contact Person First
and Last Name
MED II Summer Research Program
2018 Supervisor Abstracts
Title: Impact of Online Resources and Social Media on Breast Cancer Patients: A Survey-Based Research Study Background: Women newly diagnosed with breast cancer often seek information from online resources and social media. However, little is known about the level of consumption of specific resources, as well as the impact these might have on a patient’s sense of preparedness for initial oncology consultation, satisfaction with physician recommendations, and treatment decision-making. Methods: We will survey women with a new diagnosis of breast cancer (any stage), who have been referred to either medical or radiation oncology at CancerCare Manitoba. Baseline demographic information will be collected from the medical record. Respondents will be asked about the specific online resources and social media tools they have utilized to seek information on breast cancer since the time of diagnosis, as well as their sense of preparedness for their initial oncology visit. Following initial consultation, they will answer questions surrounding their satisfaction with the physician recommendations and treatment decision-making. Anticipated Results: Findings from this study will help the medical community better understand the uptake and impact of online resources and social media tools within the breast cancer population. Data such as these are essential should we hope to better leverage these modalities in the future to improve the breast cancer patient experience. Student Role: The student will work primarily within CancerCare Manitoba, and will have a broad exposure to all steps of conducting a successful survey-based research study. They will gain exposure to survey development and research ethics board submission (prior to the summer experience), and will have the opportunity to interact with patients when collecting survey responses. They will then summarize the data and help to analyze the results with appropriate statistical support. We anticipate the student will present these results at a national oncology conference (e.g. CAMO) with subsequent publication in a peer-reviewed scientific journal. Primary Supervisor: Dr. Danielle Desautels Medical Oncologist, CancerCare Manitoba Assistant Professor, University of Manitoba Rady Faculty of Health Sciences Email: [email protected] Phone: (204)787-1815
Title: EHealth strategies to prevent hospital admission/readmission in patients with advanced chronic diseases: a systematic review Background: Unplanned hospital admissions in high-risk patients are common and costly in an increasingly frail chronic disease population. Virtual wards (VW) attempt to reduce this risk by providing patients with a period of intensive multidisciplinary team management after discharge, employing the “systems, staffing, and daily routines of a hospital ward…” in a community-based care framework (9). VW’s are complex interventions incorporating multidisciplinary healthcare teams, eHealth communication platforms, and case management components. Work done by us has shown that VW can improve outcomes among patients with specific chronic diseases, such as with heart failure. The high cost of these intensive and complex interventions has, however, limited real-world application. It is unknown whether less complex (and therefore less costly) interventions using, for example, eHealth communication platforms or case management strategies alone (e.g. without structured interdisciplinary care), can provide similar efficacy. Methods: We propose a systematic review to address this knowledge gap. Using established systematic review methods with which we have extensive published expertise, we will identify all relevant studies examining eHealth, case management, and VW interventions in chronic diseases, including but not limited to chronic kidney, heart, and lung disease. We will summarize data on type of intervention, disease population, and efficacy in reducing hospital admission and death. Data permitting, we will conduct a meta-analysis with meta-regression to ascertain whether type and intensity of intervention (e.g. eHealth follow up vs case management vs. Formal interdisciplinary Virtual ward) influences outcome. Anticipated Outcomes: This work will help inform the optimal design of strategies to limit the morbidity and cost associated with unplanned hospitalization in vulnerable chronic disease populations. Role of the Student: The student will be responsible for working directly with the medical librarian and study investigator in order to develop the PICO (Population, Intervention, Comparison and Outcomes) literature search strategy. The student will then be responsible for screening and selecting abstracts for further comparison and inclusion in the final systematic review. If applicable, the student will work with our team biostatistician to complete the meta-analysis for comparison of different interventions, and will lead final manuscript preparation. The student will work at the Seven Oaks Hospital Chronic Disease Innovation Centre (CDIC) and will be supported by an interdisciplinary team of investigators, research coordinators, graduate students, a medical librarian and research manager. The CDIC is leading innovative research in chronic disease prevention and treatment and has a very good track record of mentoring successful students that go on to publish in academic journals and present their findings at national and international meetings. Contact Information: Michelle Di Nella (Research Manager) 204-632-3383 [email protected]
Employment in patients with recent onset inflammatory arthritis: prevalence and impact of clinical and
sociodemographic variables on work impairment at diagnosis and over time.
Supervisors Dr C Hitchon and Dr L Lim
Dr. Carol Hitchon: [email protected]
Dr Lily Lim: [email protected]
Background: Rheumatoid arthritis is a common cause of disability and lost work productivity. This
project will assess work status, absenteeism (time away from work) and presenteeism (ineffectiveness
at work) in patients with rheumatoid arthritis over time and determine clinical and sociodemographic
factors affecting employment.
Objective 1. What is the prevalence of absenteeism and presenteeism at arthritis diagnosis and what
clinical and sociodemographic factors affect work status.
Objective 2. Does work status change over time in patients with recent onset arthritis and what factors
impact this change?
Methods: The Manitoba Early arthritis cohort (n>300 with over 5 years of followup) records clinical
arthritis variables, work status (employed or not), occupation, and the work productivity and activity
impairment index (WPAI) annually. Occupation will be categorized. Descriptive statistics will assess
baseline work status and associated variables. Novel methods for analyzing longitudinal clinical data will
test associations between work status changes and function/arthritis activity over time.
Anticipated results: Work status will be affected by disease activity and occupation. Patients achieving
rapid disease control will be more likely to return to and maintain full work status. Presenteeism will be
more common than absenteeism. Patients with manual occupations will be more likely to change
occupational category than non-manual.
Role of student: The student will: 1. review background literature regarding work status and occupation
in chronic disease such as arthritis and familiarize themselves with the dataset. 2. Categorize self
reported occupation in the dataset and work with Dr Hitchon to create composite measures of disease
activity, joint counts and other covariables and perform analysis of baseline predictors of work status. 3.
Work with Dr Lim to evaluate longitudinal outcomes of work status and contributing factors. 4. Meet
adult and pediatric arthritis patients.
Title: Improving communication for colonoscopy
Background: Colonoscopy is currently the most commonly performed medical
procedure. It is used for both evaluating symptomatic individuals and colon cancer
screening (as first test or as follow-up to other tests such as fecal occult blood test) for
asymptomatic individuals. Traditionally 20-30% of individuals undergoing colonoscopy
have had poor bowel preparation which limits the effectiveness of colonoscopy in
detecting lesions, increases resource utilization due to repeat procedures and increases
risk of complications. There is a wide variation in clinical practices of follow-up after
detection of colonic polyps, which are the precursors of most of colon cancers. Colon
cancer continues to be the second most common cause of cancer related deaths.
Materials and Methods: Our group has been developing knowledge translation tools
such as video, written materials and decision aids. These materials require evaluation as
to their acceptability, utility and effectiveness in communicating important information.
We will develop both survey and interview tools to obtain feedback from patients and
analyze the results using quantitative and qualitative methods as appropriate.
Anticipated Results: We anticipate that we will obtain valuable feedback about the tools
that we can use to refine their content, format and distribution to better meet the needs of
patients. The research will also contribute to the work on evaluation methods for
knowledge translation tools focused on the information needs of the patient.
Role of the student: The medical student will be involved in refining these tools and,
primarily, in the evaluation of these tools by participating in the development,
implementation and evaluation of surveys and interviews. . Communication and
knowledge translation skills are important in building authentic relationships with
patients, and providing evidence based education and care. The student working with this
project will have the opportunity to work with an interdisciplinary team that includes
clinicians, researchers and knowledge translation specialists The student will develop
skills in survey and interview research approaches and analysis of quantitative and
qualitative data.
Title: Exploring the effects of peas on post-prandial glycaemic and satiety responses using a metabolomics approach Background: Peas are high in fibre, resistant starch, protein, and polyphenols and show great potential as a functional food. However, many studies on peas do not link the structure of the food to a functional outcome. The food used in this project will be assessed for bioactive content and we will relate these to markers of health benefit (increased satiety and lower post-prandial glycaemic response (PPGR)). This approach will capture the beneficial effects of pea components by tracking these though processing, formulation into food items and following ingestion in human studies. Methods: A randomized, controlled, cross-over study designed to examine the PPGR and satiety response to peas will be conducted at the I.H. Asper Clinical Research Institute. 24 eligible participants will attend 4 clinic visits in a fasted state. Participants will be given food containing peas at 2 visits and food without peas at 2 visits. At each visit participants will provide 7 blood samples (fasting & 15, 30, 45, 60, 90, 120 min after consuming the test food) and 2 urine samples (fasting & 120 min). Each visit will be separated by 3-14 days. Metabolites will be extracted from the plasma and urine samples for analysis using liquid chromatography-quadrupole time of flight-mass spectrometry. Several developed algorithms will be used to extract and identify entities from all biological samples analyzed. ANOVA repeated measures followed by Bonferroni correction will be performed. Data mining of untargeted LC-QTOF-MS data and all statistical analyses will be performed using Mass Professional Profiler Software. Anticipated results: Identification of pea key bioactive compounds present in biological samples and their effect on various biochemical pathways. Role of student: Extraction, metabolomics and statistical analysis of plasma and urine samples collected in the clinical trial. [email protected]
1
During the recent Ebola virus disease (EVD) epidemic of West Africa, sporadic transmission events were
reported due to sexual transmission from EVD survivors. Although Ebola virus (EBOV) transmission
occurs primarily during acute infection, there is strong evidence supporting sexual transmission from EVD
survivors and numerous reports of EBOV persistence in semen. Preliminary data suggests that infectious
virus is found in high concentrations within semen and results from active viral replication within the
testis. Pathology data suggests that seminiferous epithelium and interstitial cells at the blood-testis barrier
(BTB) are targeted by EBOV. However, EBOV cell tropism and replication kinetics within the testis are
unknown. The objective of this proposal is to characterize the molecular mechanisms of EBOV
persistence within the testis. We hypothesize that EBOV persistence in the testes is due to low-level
persistent replication mediated by defective interfering particles (DIPs) within specific BTB cell types in
the absence of cytopathology. Our aims are to: i) characterize EBOV cell tropism at the BTB; ii) determine
EBOV replication kinetics within susceptible cells; iii) identify the roles of DIPs and host cell immune
response modulation in EBOV persistence; and iv) validate our observations in a humanized mouse model
of EBOV infection.
Approach: In aim (i) we will investigate EBOV testicular cell tropism in isolated murine testicular cells
and in a 3D co-culture model of the BTB. Pseudotyped EBOV (EBOV-VSV-Luc), which is a containment
level 2 (CL2) pathogen, will be used for these analyses. In aim (ii) we will characterize EBOV replication
kinetics in susceptible cells identified in aim (i). We will investigate the role of DIPs in mediating EBOV
persistence at the BTB in aim (iii) and in aim (iv) we will utilize a humanized mouse model to validate
our observations from aims (i-iii). Experiments with wild-type EBOV will be performed at the National
Microbiology Laboratory (NML) by the Principal Investigator or NML staff.
Anticipated Results and Student Roles: Long-term viral persistence in EVD survivors could result in
incidental introductions of Ebola virus to new geographic regions, including Canada, and raises important
national and provincial public health concerns. This investigation will elucidate the molecular mechanisms
underlying this phenomenon and will have important impacts for national public health strategies during
future outbreaks, in particular with regards to post-outbreak surveillance and patient care strategies. The
student will be expected to participate in training and performance of the described research in the CL2
laboratory. These will include: i) isolation of primary murine testicular cells; ii) growth and maintenance
of 3D BTB co-cultures; iii) EBOV-VSV-Luc infections; and iv) analysis of EBOV replication kinetics by
RT-qPCR.
Development and evaluation of new therapeutic targets for multiple sclerosis Rationale: Multiple sclerosis (MS) is a progressive autoimmune condition of the central nervous system (CNS) that is characterized by immune-mediated demyelination (loss of myelin sheath around axons). MS inflicts millions of individuals world-wide who are mostly young adults. Canada has a high prevalence of MS with nearly 23.9 per 100,000 population. While functional impairments are reversible at early stages of MS due to spontaneous myelin repair, with disease progression and re-occurrence of autoimmune demyelination, axons degenerate permanently resulting in irreparable damage to the neural circuitry and neurological deficits. Currently no effective treatment strategy has been identified for MS, and development of clinically relevant therapies is critically needed. Our recent investigations in a relevant preclinical model of MS (Experimental Autoimmune Encephalomyelitis, EAE) has uncovered a link between dysregulation of Neuregulin-1 (Nrg-1) and the imbalanced immune response and impaired remyelination in MS lesions. Nrg-1 is an essential growth factor for development and function of the nervous system. Importantly, in MS patient samples, we have also verified the same Nrg-1 pathology showing the clinical relevance of our preclinical findings. Our ongoing therapeutic work in the EAE model shows the promise of Nrg-1 therapy in attenuating demyelination and fostering a pro-regenerative immune response in progressive MS lesions. Main objective: In this translational project, we will extend our initial discoveries to further evaluate the therapeutic benefits of Nrg-1 in recovery from EAE. We will administer human recombinant Nrg-1 through systemic delivery to the EAE mouse at different stages of the disease, and assess the efficacy of Nrg-1 therapy using a variety of advanced cellular, molecular and imaging techniques in vivo and in vitro. We will also evaluate neurological outcomes of Nrg-1 treatment. Impact and translational feasibility: Neuregulin-1 is a drug approved by the US Food and Drug Administration (FDA) meaning that it is safe for patients. Additionally, Neuregulin-1 has ideal pharmacokinetics enabling its entry to the brain and spinal tissue via the blood-brain-barrier. Thereby, if our therapeutic work shows beneficial effects, Neuregulin-1 has high translational feasibility as a new target for MS.
Role of the BSc MED Student Summer Researcher: The BSc Med student would have the opportunity to work closely with our research team to contribute to this comprehensive project. The student will be trained by senior member of our team to participate in cellular and histopathological assessments of spinal cord tissue and tissue culture samples. The student will be credited for the data they provide for the project. Karimi's laboratory is supported by the Multiple Sclerosis Society of Canada. The laboratory is located in the Regenerative Medicine Program in the Faculty of Medicine. Lab homepage: http://home.cc.umanitoba.ca/~karimis/
Contact information:
Dr. Soheila Karimi
Regenerative Medicine Program 629-Basic Medical Sciences Bldg 745 Bannatyne Ave., Winnipeg MB R3E 0J9 Email: [email protected] Tel: 204-272-3109
Awake craniotomies under 3-Tesla Intraoperative Magnetic Resonance Imaging: A Descriptive Study and Our Institutional Experience 1. Introduction
Intraoperative MRI (I-MRI) is a new and novel real-time imaging technique in the field of neurosurgery and enables precise identification of brain tumors and allows for tumor resection with a higher safety margin. Awake craniotomy is the current technique most commonly used to remove brain lesions in eloquent (functionally important) regions of the brain.Therefore, the combination of I-MRI and awake craniotomy techniques should provide the greatest precision and highest safety margin in the resection of brain tumors. Interestingly, the University of Manitoba (Health Sciences Center, KIAM Center) is one of a few academic centres globally that uses a 3-T I-MRI operating room suite. This ongoing study will investigate the role of I-MRI in patients undergoing awake craniotomies. 2. Methods This is an ongoing retrospective database study. It has ethics approval. Data Collection Demographic and perioperative data will be collected as well as intraoperative data including type of anesthesia and duration, surgical duration, etc. Postoperative complications and mortality within 6 months of surgery will be recorded. Endpoints To assess the primary endpoint, trends in overall postoperative morbidity (new neurological deficits/ exaggeration of pre-existing deficits) will be compared between the three groups of patients. Secondary outcomes include anesthetic complications, surgical complications, length of hospital stay, cost effectiveness, duration of anesthesia, duration of surgery and overall mortality. 3. Expected Results This study may demonstrate that the combination of I-MRI and awake craniotomy has a lower relative risk. 4. Expected Conclusions We anticipate that the study will provide data and recommendations for our own centre as well as other global centres in conducting awake craniotomies safely and effectively under I-MRI. The study will also help plan future randomized control trials. 5. Student’s role
This will be a great learning opportunity. 1. The student will get to know about awake craniotomy as well as I-MRI. 2. He / she would able to see the live case as well. 3. He / she would collect the data, analyze and able to interpret as well as prepare manuscript. 4. He / she would have an opportunity to present the abstract at various conferences.
Investigating the Neuroprotective Role of Neuregulin-1 in Traumatic Spinal Cord Injury Introduction and Rationale: Spinal Cord Injury (SCI) results in significant cell death and tissue degeneration causing complete loss or dysfunction of sensory, autonomic, and motor function in patients at and below the site of injury. To date, no effective treatment option has been identified for SCI, and there is substantial incentive for developing regenerative medicine therapies for this condition. Extensive preclinical research from our group and others has convincingly shown the promise of neural stem cell (NSC) therapies for SCI. Indeed, based on these preclinical findings, NSC transplantation has moved to clinical trials in recent years. Initial outcomes of these trials indicate that NPCs are safe and hold promise as a treatment strategy for SCI, however, their benefit for neurological recovery is rather modest. This is mainly attributed to the limited survival, integration and differentiation of engrafted NSCs in the impermissible milieu of SCI, establishing a need for development of combinatorial strategies to augment transplant survival and cell replacement in SCI.
We have made the original discovery that both SCI and multiple sclerosis result in acute and permanent depletion of Neuregulin-1 (Nrg-1), a critical factor for NSC differentiation and survival. In a preclinical model of traumatic SCI, we demonstrate that Nrg-1 therapy promotes endogenous replacement of myelin-forming oligodendrocytes and fosters a positive immune response that culminates in improved neurological recovery. Importantly, our initial stem cell transplantation studies indicate that Nrg-1 co-therapy can optimize the long-term survival of engrafted NSCs in SCI suggesting a neuroprotective role for Nrg-1 that needs further elucidations. Main Objective: In this translational project, we will evaluate the neuroprotective effects of Nrg-1 therapy on the survival and function of NSCs following injury using parallel in vivo and in vitro models. We will administer human recombinant Nrg-1 to rats with contusive SCI at the time of NSC transplantation by systemic delivery. In vitro, primary adult spinal cord derived NSCs will be exposed to SCI-relevant conditions such as glutamate excitotoxicity and hypoxia. Using an array of advanced cellular, molecular and imaging techniques, we will assess the efficacy of Nrg-1 in optimizing NSC survival as well as their ability for cell differentiation and migration under injury conditions. We will also evaluate neurological benefits of NSCs transplantation and Nrg-1 co-therapy following SCI.
Impact and translational feasibility: Nrg-1 is a drug approved by the US Food and Drug Administration (FDA) that has been used in a Phase II trial for cardiac dysfunction meaning that it is safe for patients. Importantly, Nrg-1 has ideal pharmacokinetics enabling its entry to the brain and spinal cord tissue via the blood-brain-barrier. Thereby, if our therapeutic work shows beneficial effects, Nrg-1 has high translational feasibility as a new therapeutic target for SCI.
Role of the Med II Student Researcher: The Med II student would have the opportunity to work closely with our research team to contribute to this comprehensive project. The student will be trained by senior member of our team to participate in cellular and molecular assessments related to the proposed in vitro studies. If interested, the student will also have the opportunity to observe our SCI procedures in vivo. The student will be credited for the data they provide for the project. Our laboratory is located in the Regenerative Medicine Program in the Rady Faculty of Health Sciences.
Contact information:
Dr. Soheila Karimi Regenerative Medicine Program 629-Basic Medical Sciences Bldg. Max Rady College of Medicine Email: [email protected], Tel: 204-272-3109 Lab homepage: http://home.cc.umanitoba.ca/~karimis/
Investigating Potential Bio-Markers for FASD “Fetal Alcohol Spectrum Disorders (FASD)” refer to a range of neurological disorders that are associated with morphological abnormalities and compromised brain function due to prenatal exposure to alcohol (ethanol). FASD are neurodevelopmental disorders that affect 1-3% of live born children due to in utero exposure to ethanol via alcohol drinking of their pregnant mother. Currently, FASD has no cure and the underlying cellular biology of FASD is not fully understood. We have recently reported how ethanol deregulates the epigenetic programing of embryonic brain cells. We showed that chromic ethanol exposure not only alters DNA methylation at specific genetic loci, but it also impacts the global DNA methylation levels. Using cutting edge stem cell and molecular biology techniques, we have conducted comprehensive studies in embryonic brain cells to study the genome-wide deregulatory role of chronic ethanol exposure. With a team effort and combination of bioinformatics analysis and molecular biology techniques, we have identified putative candidate genes that we now aim to validate in human cells as potential biomarkers for FASD. Translation of our data from murine to human cells is critical for identifying future clinical biomarkers for FASD. In this project, we will investigate the conservation of identified putative biomarkers from mice to human cells. We will determine the effects of chromic ethanol exposure during differentiation of human cells and characterize potential change in cell fate determination of brain cells. Our results will have significant impact for early diagnosis of FASD in the future, which would be critical for early intervention therapeutic strategies. Student’s Role: The student will be responsible for multiple techniques associated with this study, including protein and RNA extraction from the collected samples and performing Western Blot and RT-PCR experiments as well as analyzing the data. The student will also be responsible to be up to date with regards to the literature related to this project. Supervisor: Mojgan Rastegar, PhD, Associate Professor Biochemistry & Medical Genetics, Regenerative Medicine Program Max Rady College of Medicine, Rady Faculty of Health Sciences University of Manitoba, 745 Bannatyne Avenue Rm.627, Basic Medical Sciences Bldg. Winnipeg, MB R3E 0J9, Canada Phone (office): (204) 272-3108 Phone (lab): (204) 272-3145/ Fax: (204) 789-3900 [email protected] http://rastegar.biochem.umanitoba.ca/
Epigenetic control of gene regulatory network of neural stem cells Neural stem cells (NSC) are primary progenitors with the ability of self-renewal and differentiation into different cell types within the central nervous system of the embryonic and adult brain. Neural stem cells are widely accepted biological systems to study the basics of mammalian neurogenesis, the process in which new neurons are produced in the brain. Despite our current progress to direct NSC differentiation, we still face considerable challenge to produce pure populations of specific brain cell types for cell-based therapy strategies in regenerative medicine. Understanding the mechanisms of NSC differentiation is crucial, since they can be used to replace cells, which are lost or damaged in brain stroke, trauma, spinal cord injury, and other neurological disorders such as Parkinson’s or Alzheimer’s disease. Our preliminary results indicate that gene regulatory networks of brain cells are regulated in an X-linked-specific manner and by epigenetic mechanisms. Currently, the X-linked gene regulatory mechanisms and the epigenetic mechanisms that are involved in NSC self-renewal and differentiation are not fully known. Using cutting edge technologies in stem cell biology, we will study the dynamics of selected X-linked regulatory networks in male and female NSC isolated at different stages of development and will investigate their functional role in neural stem cell fate decisions. This project will address fundamental unanswered questions on neural stem cell differentiation and self-renewal, highlighting the role of important developmentally regulated genes and epigenetic factors in NSC fate commitments. Our studies will have future applications towards stem cell-based therapy strategies in regenerative medicine, with significant impact on underlying gender-bias mechanisms of specific neurological disorders. Student’s Role: The student will be responsible for isolation, culture and differentiation of brain-derived neural stem cells during embryonic development. He/She will collect protein and RNA samples at different time-points in self-renewing and differentiating neural stem cells and will perform Western Blot, RT-PCR and IF experiments for selected genes and will analyze the data. The student will also be responsible to be up to date with regards to the literature related to this project. Supervisor: Mojgan Rastegar, PhD, Associate Professor Biochemistry & Medical Genetics, Regenerative Medicine Program Max Rady College of Medicine, Rady Faculty of Health Sciences University of Manitoba, 745 Bannatyne Avenue Rm.627, Basic Medical Sciences Bldg. Winnipeg, MB R3E 0J9, Canada Phone (office): (204) 272-3108 Phone (lab): (204) 272-3145/ Fax: (204) 789-3900 [email protected] http://rastegar.biochem.umanitoba.ca/
Targeting Cell Signaling by FDA-Approved Drugs in Medulloblastoma Brain Tumor Medulloblastoma is a high-grade, malignant, and rapid growing pediatric brain tumor that resides in the cerebellum. Medulloblastoma is considered to be the most common tumor originating from the immature cells of the developing brain. In about 70% of cases, medulloblastoma is developed in young children that are below the age of 10. It is well documented that fundamental cellular mechanisms control the normal proliferation of cells, which are deregulated at multiple levels in cancer cells. This includes regulation of gene expression, and modulation of key signaling pathways that target mTOR, and the oncogenic protein RAS. In a primary screen of FDA-approved drugs, we have discovered a selective anti-proliferative role for specific FDA-approved drugs. Importantly, we only detected such anti-cancer effects in human medulloblastoma cells, but not in normal human cells. In this project, we will study the mechanisms of our detected anti-cancer effects for these FDA-approved drugs in human medulloblastoma cells. While the effects of these drugs on RAS and mTOR pathways are well documented in other cell types, involvement of RAS and mTOR cell-signaling pathways for these drugs are not studied in medulloblastoma. Our results will have significant therapeutic outcome for medulloblastoma as the most common brain tumor in children. Student’s Role: The student will be responsible for multiple techniques associated with this study, including cell culture and drug-treatments, viability tests, protein and RNA extraction from the collected samples, as well as performing Western Blot and RT-PCR experiments, and analyzing the data. The student will also be responsible to be up to date with regards to the literature related to this project. Supervisor: Mojgan Rastegar, PhD, Associate Professor Biochemistry & Medical Genetics, Regenerative Medicine Program Max Rady College of Medicine, Rady Faculty of Health Sciences University of Manitoba, 745 Bannatyne Avenue Rm.627, Basic Medical Sciences Bldg. Winnipeg, MB R3E 0J9, Canada Phone (office): (204) 272-3108 Phone (lab): (204) 272-3145/ Fax: (204) 789-3900 [email protected] http://rastegar.biochem.umanitoba.ca/
Background
Approximately 10-20% of patients believe they are penicillin allergic. However, a study conducted by the co-
supervisors of this proposal and a medical student demonstrated that in a sample of 306 predominantly
pediatric patients evaluated for penicillin allergy about 96.1% could tolerate penicillin after allergy evaluation.
Patients reporting penicillin allergies are more likely to receive broad-spectrum antibiotics which have been
linked to antibiotic resistance and increased health care costs.
There is no Canadian data regarding self-reported rate of penicillin allergy. This study aims to describe the
prevalence of beta-lactam allergy in Canada using the country’s largest multi-disease sentinel surveillance
network.
Methods
The Canadian Primary Care Sentinel Surveillance Network (CPCSSN) collects and processes de-identified
Electronic Medical Record (EMR) data from consenting community-based primary care practices. The CPCSSN
repository includes information from over 300 clinics (1200 providers, 1.5 million patients) across Canada.
CPCSSN has developed and validated methods to evaluate and define several medical conditions.
We propose the development of an algorithm for documented penicillin allergy based on the extracted EMR
records held in the CPCSSN repository. We will apply the definition to all patients seen at least once in the
previous 2 years and who are alive at the time of data extraction in order to describe the prevalence. The
patients with documented penicillin allergy will be explored using descriptive statistics.
Anticipated Results
We expect to find results similar to international studies (10-20% of the population). This will be a precursor
for studies designed to address this issue.
Role of the student
The student will assist the CPCSSN data manager as the clinical expert to validate the algorithms that will
define penicillin allergy.
The student will then be responsible for conducting the descriptive statistical analysis in consultation with a
CPCSSN epidemiologist. Once results are available the student will prepare the first draft of the manuscript in
consultation with the primary investigators.
Alexander Singer MB BAO BCh CCFP [email protected] Associate Professor, Department of Family Medicine Network Director of the Manitoba Primary Care Research Network Elissa Abrams MD FRCPC Lecturer, Department of Pediatrics, Section of Allergy and Clinical Immunology