The teams are two out of seven research groups from across Canada to be awarded funding as part of CIHR’s initiative to better understand the role of the microbiome in human health and disease.

Microbiome in cervical cancer

One Rady Faculty of Health Sciences research team received funding for a five-year project to allow the scientists to perform studies of the vaginal microbiome in cervical cancer to better understand its role in the disease.

“Cervical cancer is one of the most common cancers in women globally, causing more than 250,000 deaths per year and affecting more than half a million women each year,” said co-lead Dr. Adam Burgener, associate professor of obstetrics, gynecology and reproductive sciences, and medical microbiology and infectious diseases. “The HPV vaccine is the most effective prevention tool we have against cervical cancer. But for those with advanced disease, where treatment options are more limited, finding new therapeutic interventions that could help existing treatments would be very helpful. We are very excited and grateful for the support from CIHR to help with this effort.”

(Left to right) Dr. Adam Burgener, Dr. Vanessa Poliquin and Dr. Thomas Murooka.

Along with Burgener, the project will be co-led by the Rady Faculty’s Dr. Thomas Murooka, assistant professor of immunology and medical microbiology and infectious diseases, and Dr. Vanessa Poliquin, assistant professor of obstetrics, gynecology and reproductive sciences, and Dr. Roger Paredes, from the IrsiCaixa Institute for AIDS Research in Spain.

The study will investigate whether healthy vaginal bacteria, such as lactobacillus species, or the products they produce, such as metabolites and proteins, are important for slowing the progression of cervical cancer. The project will not only study the microbiome, but also immune responses that are important for clearance of the disease, using the tools of systems biology. Burgener’s team hopes that by examining this ‘cross-talk’ between the immune system and the microbiome it could lead to useful therapeutic interventions.

“The microbiome is very important for the susceptibility to many diseases,” Burgener said. “It is being explored for treatments in disease, including cancer. For example, the absence of some microbial species in the gut have been shown to determine whether certain cancer therapies are effective or not. This is truly remarkable, as it indicates they could act as partners in therapy. It may be that the vaginal microbiome may hold similar potential against cervical cancer, and we hope to find it.”

Co-investigators on the project include Dr. Alicia Berard (University of Manitoba), Dr. Christina Farr (University of Manitoba) and Dr. Melanie Murray (University of British Columbia). Clinical partners working in Uganda include Dr. Lisa Frenkel (University of Washington), Dr. Tom Uldrick (University of Washington), Dr. Carolyn Nakisige (Uganda Cancer Institute), Dr. Constance Namirembe (Uganda Cancer Institute) and Dr. Corey Casper (University of Washington). Dr. Jiafen Hu (Penn State Cancer Institute), Dr. Jake Estes (Oregon Health and Sciences University), Dr. Rafick Sekaly (Case Western Reserve University) and Dr. Alberto Severini (PHAC) are collaborators on the project.

Microbial causes of asthma

The other team, made up of CHILD Cohort Study researchers, received funding for a five-year project to allow the scientists to examine the trillions of microorganisms living inside the human body and uncover the role they play in causing asthma.

“Asthma affects about one in 10 children and it is the most common reason why children miss school or end up in hospital,” said co-lead Dr. Meghan Azad, Canada Research Chair in Developmental Origins of Chronic Disease at the University of Manitoba and a research scientist at the Children’s Hospital Research Institute of Manitoba. “We are truly delighted to receive this funding, which will ultimately help us to improve the lives of Canadian children.”

Dr. Meghan Azad and Dr. Padmaja Subbarao.

The study is co-led by Azad and Dr. Padmaja Subbarao at The Hospital for Sick Children in Toronto.

The project, Causational Roles of the Gut Microbiome in Childhood Asthma: Leveraging the CHILD Co-hort Study, will mine the extensive environmental, clinical and microbiome data, and biological samples available from CHILD to investigate how an infant’s genetics, sex and early-life exposures influence the microbiome-immune system co-development. The project will also look at the importance of breastmilk and antibiotics in shaping the infant gut microbiome; the impact of the microbiome on the risk of asthma; and microbiome-targeted interventions for asthma in mice.

“CHILD has shown that breastfed babies have higher levels of beneficial gut bacteria and a lower risk of developing asthma as they get older,” Azad said. “This research will use new technologies to find out how gut bacteria are causing or preventing asthma and the role that early-life exposures, such as breastfeeding, play in modifying those bacteria.”

Launched in 2008 by CIHR and AllerGen NCE, the CHILD Cohort Study (CHILD) is tracking nearly 3,500 Canadian infants and their families, including 1,000 in Manitoba, to help determine the root causes of chronic diseases such as asthma, allergies and obesity. CHILD spans four provinces, involving over 140 multidisciplinary researchers, students and research staff.

Principal Investigators on the project include Dr. Qingling Duan (Queen’s University), Dr. Jeremy Hirota (McMaster University), Dr. Anita Kozyrskyj (University of Alberta), Dr. Wendy Lou (University of Toronto), Dr. Kelly McNagny (The University of British Columbia), Dr. Michael Surette (McMaster University), and CHILD co-director Dr. Stuart Turvey (The University of British Columbia).

The Canadian Institutes of Health Research (CIHR) has provided significant funding to two Rady Faculty of Health Sciences professors: Medical microbiologist Dr. Keith Fowke and his team will receive $2 million dollars over five years to investigate how anti-retroviral and anti-inflammatory medications can prevent new HIV infections; and Obstetrics and Gynecology professor Adam Burgener and his team will receive $2 million dollars over five years to investigate how the microbiome in the human body interacts with vaccines and anti-retroviral drugs against HIV.

“I congratulate Drs. Fowke and Burgener on their success in this competitive funding award,” said Digvir Jayas, vice-president (research and international) and Distinguished Professor at the U of M. “Their teams are made up of national and international experts who I have no doubt will make inroads in their investigations, for the benefit of all.”

On July 17, the Honourable Ginette Petitpas Taylor, Canada’s Minister of Health, announced an investment of more than $32 million in sexually transmitted and blood-borne infections research from the Government of Canada, through the Canadian Institutes of Health Research (CIHR).

The University of Manitoba has long been at the forefront of HIV/AIDS research, running a collaboration with the University of Nairobi since 1980, significantly advancing the world’s understanding of HIV/AIDS with monumental discoveries such as the virus being transmitted through heterosexual partnerships and from mother to child through breast milk; they also discovered a group of sex workers seemingly immune to the virus, to name just three discoveries.

Fowke’s [BSc(Hons)/88, PhD/95] and Burgener’s [BSc(Hons)/99, PhD/05] new projects continue to uphold this established track record.

Fowke’s project: Combination HIV Prevention: Using anti-retroviral and anti-inflammatory medications to prevent new HIV infections

Co-Principle investigators: Emmanuel Ho (University of Waterloo); Joshua Kimani (Medical Microbiology and Infectious Diseases (MMID – U of M and University of Nairobi); Lyle Mckinnon (MMID-UM); Thomas Murooka (Department of Immunology-UM); Julie Lajoie (MMID-UM); Julius Oyugi (MMID and University of Nairobi)

Just as cancer therapy attacks with multiple drugs, this team will employ a combination of biomedical approaches that blocks HIV infections in different ways.

Firstly, they will use anti-HIV drugs that work by blocking the ability of the virus to replicate. Secondly, they will block the inflammatory process that brings the cells that HIV primarily infects into the genital tract using anti-inflammatory drugs. Based on research pioneered by their team members, they have shown that inflammation greatly increases the risk of HIV transmission and can actually nullify the effects of anti-HIV drugs to prevent infections. In one of their pilot studies, for instance, they showed that the anti-inflammatory drug aspirin (acetylsalicylic acid, or ASA) reduces the number of HIV target cells in the genital tract by 35 per cent. They will now further investigate this connection.

Working with a cohort of female sex workers in Nairobi, Kenya who are highly exposed to HIV and are using anti-HIV drugs for prevention, the team will place women with high levels of genital inflammation on the anti-inflammatory drug ASA to assess if the number of HIV target cells in the genital tract is reduced. Meanwhile, in the laboratory, they will use mice with a human immune system to determine the mechanism of how ASA affects the migration of HIV target cells and they will perform HIV infection studies to directly test is ASA can reduce HIV infection.

Finally, because taking drugs daily can be challenging for some people, the team will assess in the humanized mouse model, the long-term goal of using an intravaginal ring that would deliver a contraceptive, an anti-HIV drug, and an anti-inflammatory drug. This proposal will determine if their “Combination HIV Prevention” approach is more effective, thereby providing women with more options for protecting themselves.

Burgener’s project: The microbiome in HIV prevention

Co-Principle investigators: Carolina Herrera (Imperial College, London); Roger Paredes (Irsi Caixa, Barcelona)

Co-Investigators: Vanessa Poliquin (Obstetrics, Gynecology and Reproductive Sciences, U of M) and Thomas Murooka (Department of Immunology-UM)

The microbiome has been associated with increased risk of HIV acquisition, but this has not been studied extensively in the context of HIV prevention technologies, such as anti-retroviral based pre-exposure prophylaxis and vaccines. In this study, Burgener and his team will evaluate how differences in the microbiome of genital tract and gut affect host inflammation, the effectiveness of these drugs, and immune responses stimulated by HIV vaccines. These studies may help us to improve these products to make them more effective for HIV prevention.

This project, in collaboration with IrsiCaixa AIDS Research Institute, builds on Burgener’s past work that discovered the effectiveness of an anti-HIV gel known as tenofovir is related to the presence of “healthy” lactobacillus bacteria in vaginal tract, meaning those women who lacked this bacteria gained little or no benefit from the drug.  

“This was a striking result, and made us think that there was some interaction between some bacteria and tenofovir,” Burgener, who is also a Research Scientist with the Public Health Agency of Canada, said at the time.

Burgener’s team was the first to show that vaginal bacteria can impact this class of anti-retroviral drugs, and their efficacy can vary more than three-fold depending on what bacteria are dominant in the person.