Here are the projects chosen for funding in 2019:
Medications in Milk
Many women require medications for chronic or acute conditions postpartum, such as infections, inflammatory diseases or depression. Breastfeeding provides optimal nutrition for newborns. Concerns about medication safety present a potential barrier to breastfeeding. Women and healthcare providers need to be able to make informed decisions about the risks and benefits of breastfeeding while taking a medication.
Our objectives are: 1. To develop a multidisciplinary team to evaluate medications in breastmilk through the Manitoba Interdisciplinary Lactation Centre (MILC); 2. To identify commonly used medications during lactation by women in Manitoba; 3. To develop and pilot prospective breastmilk collection methods; and 4. To develop and pilot drug analysis protocols for the five most commonly used medications during breastfeeding.
Our multidisciplinary research team is led by Dr. Kelly, a pharmacologist, in collaboration with Drs. Meghan Azad, Nathan Nickel, Christine Leong and Kellie Thiessen. In order to establish a concrete long-term “medications in milk” research program, we need to determine what medications women are using during lactation in Manitoba and work with the community to develop protocols for prospective milk collection, drug analysis, and linking samples with administrative databases for long-term follow-up.
This information will provide robust evidence on medication safety during breastfeeding and factors which may contribute to the overall health of both mother and infant.
Artificial Intelligence in Health: A Multidisciplinary Research Team
A recent editorial in JAMA stated: “Machine learning is a valuable and increasingly necessary tool for the modern healthcare system.” The Innovation Fund grant will support a new research team within the Rady Faculty of Health Sciences by creating the infrastructure required to conduct world-class machine learning using health information.
We plan to harness the power of artificial intelligence (AI) to improve fracture prediction by analyzing bone density DXA scans to identify patterns that indicate high fracture risk. Our research team has recently achieved impressive results in applying deep learning methods to image processing for vertebral fracture recognition from DXA scans. In so doing, we have encountered and overcome many of the challenges that confront those wishing to use machine-learning techniques for image analysis in terms of computational requirements, specialized programming skills, and the need for a standardized approach to model development.
The grant will support our research team during the next year as it transitions from a successful project to a broad-based program of research, with the aim of collaborating with and assisting other researchers within the Rady Faculty of Health Sciences to enter this fast-paced field.
Our objectives over the next year are:
Our core research team includes: Dr. William Leslie, Department of Internal Medicine (endocrinology); Dr. Andrew Goertzen, Department of Radiology (medical physics); Dr. Jamie Falk, College of Pharmacy; Dr. Sheldon Derkatch, Department of Radiology (neuroradiology); Dr. Mark Bryanton, Department of Radiology (nuclear medicine); Dr. Patrick Martineau, Department of Radiology (nuclear medicine).
Our work benefits from a network of local and international collaborators. Our proposal benefits from established collaborations with the Canadian Multicentre Osteoporosis Study (CaMos); University of Minnesota; University of Lausanne; Canadian Longitudinal Study on Aging (CLSA); and University of Sheffield.
Novel Approaches to Stratifying Risk in Thyroid Cancer Sub-types
In this project, a newly formed multidisciplinary team from the University of Manitoba (Drs. Mai, Gartner and Pathak) with two collaborating experts from Italy (Drs. Vanni and Caria) will embark on a novel study aimed at resolving important diagnostic challenges in thyroid cancer.
This study will focus on a newly described entity within this group of cancers called “non-invasive follicular thyroid neoplasm with papillary-like nuclear features” (NIFTP). NIFTP requires precise characterization in order to predict its behaviour and tailor specific clinical management. Recent work by Drs. Mai and Gartner in several other tumors has demonstrated that the structural genomic organization of tumor cells and tumor cell stages displays significant differences in their 3D nuclear telomere organization and the 3D nuclear organization of DNA.
In this study of thyroid cancer, we will examine the structural genomic organization of NIFTP and compare it to other histotypes of papillary thyroid cancer. We will then determine both structural 3D molecular profiles and correlate these findings with the genetic profiles of these tumors. Some of our preliminary work has shown that studying the 3D nuclear architecture of papillary thyroid cancer is feasible in archived tissue sections and will allow us to investigate both nuclear telomere profiles and nuclear DNA structure. This preliminary study found statistically significant differences between thyroid tumor histotypes with both assays. Our study has three aims:
This project will lead to the identification of novel biological parameters to refine the diagnostic criteria for NIFTP and to determine what additional therapeutic measures might be implemented at the time of diagnosis. As a result, the findings are expected to impact on clinical practice by providing objective, actionable information, to more clearly define NIFTP and predict its outcome.
Genetic Control of Genital Inflammation
There are an estimated 37 million individuals currently living with HIV globally and about 1.8 million new cases per year. Locally, there are about 75,000 HIV-infected Canadians, with Manitoba having among the highest per capita rates nationally. While significant progress has been made in confronting the epidemic, the number of annual new infections is not declining at a rate needed to meet UNAIDS targets for epidemic control.
Given their disproportionate risk for HIV infection, young women have been identified as a key population on which to focus HIV prevention efforts. Our project builds on the observations that genital tract inflammation both enhances HIV susceptibility and undermined a partially protective HIV prevention product (tenofovir gel). While these associations are strong, the underlying causes for why some women exhibit this inflammation trait are unclear.
We have recently carried out a genome-wide genetic screen in about 240 young women who participated in a large HIV prevention trial in South Africa, to address the question of whether an individual’s genetic background could mediate their propensity toward genital inflammation. We observed a region on chromosome 19 containing 10 genes of the zinc finger family with several genetic variants that were associated with both genital inflammation and/or HIV acquisition.
Zinc finger proteins are a large, diverse family of proteins involved in multiple biological processes, including regulation of gene expression, development and immunity. The observation that inflammation-associated variants also predicted HIV acquisition risk confirms that inflammation may be a useful “intermediate phenotype” to better understand the genetics of HIV risk.
In this project, we will undertake two important aims to follow up on these observations: 1) to scale up and validate this finding in an expanded sample of South African and Kenyan women, where relevant mucosal specimens are available; and 2) to use model systems to explore the mechanisms for how these genes influence inflammation and HIV susceptibility.
Our team consists of early/mid-career investigators within the Rady Faculty of Health Sciences with complimentary expertise and a proven track record of excellence in HIV research. Dr. Lyle McKinnon (PI, Medical Microbiology and Infectious Diseases) has expertise in mucosal immunology and clinical research in Africa; Dr. Paul McLaren (Medical Microbiology and Infectious Diseases) is a leader in the field of HIV host genomics; Dr. Thomas Murooka (Immunology) is an expert in immunology and HIV model systems; and Dr. Marissa Becker (Community Health Sciences) has substantial global experience in clinical research, epidemiology and HIV transmission dynamics.
All Co-PIs have published extensively in the HIV field, with more than 140 combined publications in the past seven years, and have collaborated together on at least five funded CIHR grants. The inflammation data founding this proposal was recently published in Nature Medicine (led by Co-PI McKinnon), and the Transitions cohort was funded by CIHR (Co-PI Becker), demonstrating international and national recognition for this research.
The goal of this project is to translate discovery from genome-wide genetic studies into mechanistic understanding of HIV biology with the goal of developing novel anti-HIV treatment strategies. The combination of population-based human genetic data coupled with relevant model systems to investigate function is a novel approach in HIV prevention.
Genome-wide studies of other disease models have shown incredible promise in translating genetic discovery into treatment strategies, in therapies for myocardial infarction, Type 2 diabetes and autoimmunity. Our study uniquely combines behavioral, demographic, genomic and immunologic investigations to provide a full understanding of novel factors impacting inflammation in a key HIV at-risk population with relevance to Canada and globally.