Several MIRC members received awards at the annual Faculty of Health Sciences Research Plenary Awards Reception, which took place on May 31, 2017 in the Jan and Mien Heersink Reading Pavilion and marked the culmination of the FHS Research Plenary. The event opened with welcoming remarks from Dr. Paul O’Byrne, the Dean and Vice-President of the Faculty of Health Sciences, as well as Dr. Catherine Hayward and MIRC’s own Dr. Jonathan Bramson. Awards were then presented to winners of the Research Plenary Awards, special student and faculty awards, and Graduate Program Awards. The reception was well attended by MIRC trainees, staff and faculty, and we would like to congratulate the following individuals on their awards:
Faculty of Health Sciences Graduate Programs Outstanding Excellence Award, given to students “who achieved a rating of excellent for their last two or more supervisory committee meetings or who have received 'Distinction' on their comprehensive examinations”: Matthew Atherton, Ehab Ayaub, Steven Cass, Anisha Dubey, Amanda Lee, Dessi Loukov,
Faculty of Health Sciences Graduate Programs Outstanding Achievement Award, given to “graduate students in their final year of a Master's or Doctoral program who have made outstanding achievements, based on the opinion of their graduate program”: Matthew Atherton, Anisha Dubey, Amanda Lee, and Pavithra Parthasarathy
FHSPDA Excellence in PDF Supervision Award, given a faculty member in the FHS who has “demonstrated outstanding mentorship/supervision of postdoctoral fellows”:
FHS Research Plenary Outstanding Oral Presentation Award: Dr. Jocelyn Wessels (PDF) and Puja Bagri (Doctoral)
FHS Research Plenary MILO Commercial Potential Award: Sophie Poznanski (Masters)
FHS Research Plenary Excellence in Poster Presentation Award: Sophie Poznanski (Masters) and Danielle Vitali (Masters)
In a study published in the Journal of Infectious Disease, Dr. Yushi Yao, a postdoctoral fellow in Dr. Zhou Xing’s lab, shows a new TB vaccine testing system utilizing humanized mice (Hu-mice). By using Hu-mice developed by Dr. Ali Ashkar’s lab, Yao et al. showed that a novel virus-vectored (VV) respiratory mucosal tuberculosis (TB) vaccine developed in their lab which has undergone phase I human studies, was able to activate T cells in Hu-mice as it does in humans. Post-immunization, respiratory mucosal (RM) immunization resulted in greater antigen-specific, poly-functional CD4 T cell responses in the lung, compared to parenteral immunization. Post-M. tb infection, RM-immunized mice had significantly more CD4 T cells in the airways and lung. The vaccine was able to reduce human-like lung TB outcomes (illness scores, lung M. tb bacillary burden, lung pathologies) when administered through the respiratory route, but not the parenteral route, further emphasizing the importance of mucosal vaccination. This study demonstrates that the Hu-mice model is a suitable model to test the potency of TB vaccines and strategies, and that the novel respiratory mucosal VV immunization strategy can significantly improve lung TB protection in a T cell-dependent manner.
Congratulations to Amanda Lee, a PhD candidate in Dr. Ali Ashkar's lab, on her recent publication in the Journal of Experimental Medicine. The elaborate study thoroughly describes the mechanism by which NK cells are activated during mucosal viral infection. Using an in vivo mouse model of vaginal HSV-2 infection, Lee et al. showed that type I IFNs signal through inflammatory monocytes to produce IL-18, which then activates NK cells to produce IFN-gamma and augments protection against HSV-2 infection. The study was featured on the IIDR website,and the full study can be found here.
Endotoxin, or LPS tolerance, is an immunomodulatory mechanism that protects the host against secondary LPS exposure and may prevent endotoxic shock. During the development of tolerance, LPS binds to TLR4 and signals the release of cytokines including type I IFN, which has shown to have immunomodulator properties. The role of type I IFN in the induction of LPS tolerance was the topic of interest in a recent publication by Dr. Ali Ashkar’s research group. The study, led by former undergraduate thesis student Yalda Karimi, suggests that type I IFN does not play a role in LPS tolerance in vitro. Examining peritoneal macrophages from both wild type and IFNR KO mice in vitro, they showed that there is comparable, reduced cytokine production after secondary LPS exposure. In addition, both strains of mice received small doses of LPS to induce tolerance, and were then protected from a lethal dose of LPS. The results from this study show that unlike what was expected, type I IFN does not seem to play a role in endotoxin tolerance, and further studies are required to understand the exact mechanisms leading to tolerance. Read the full study here.
Thanks to everyone for coming to show their support for March for Science!
Individuals who are allergic to foods such as nuts and shellfish, suffer from these allergies for the entirety of their lives, with no disease-transforming therapies currently available. Better understanding food allergy is an important area of research in Dr. Manal Jordana’s lab and a recent study led by post-doctoral fellow Dr. Rodrigo Jiménez-Saiz that was published in the Journal of Allergy and Clinical Immunology, looks at the underlying mechanisms involved in allergic responses to food allergens. The conventional belief is that lifelong IgE in food allergy is due to the generation of IgE-producing plasmablasts by germinal center B cells.
These IgE-producing plasmablasts travel to the bone marrow, where they secrete IgE for the rest of an allergic individual’s life. However, this study shows a novel mechanism to explain persistent IgE in allergic responses. Using various animal models and in vitro assays, Jiménez-Saiz et al. showed that lifelong food allergy is the result of the activation of allergen-specific long-lived memory B-cells, which upon allergen re-exposure, replenish allergen-specific IgE-secreting plasma cells in an IL-4-producing CD4 T cell dependent manner. This is a novel finding, and is especially impressive due to the extremely rare population of antigen-specific IgE+ memory cells that Drs. Jiménez-Saiz and Chu were able to study in the animals across a prolonged period of time.
Furthermore, this work suggests that lifelong food allergies may be the result of re-exposure to allergens which recurrently activate memory B and CD4 T cells, and that the mechanisms involved in activating and maintaining these memory responses should be targeted in the search of potential therapies for IgE-mediated food allergies. The paper is now available to read online here. Congratulations to Rodrigo, and the entire Jordana lab for this great work and achievement!
A new study published in Cell Host and Microbe by Dr. Dawn Bowdish’s group, demonstrates the effect of the aging on the microbiota and how these changes drive intestinal permeability, age-associated inflammation, and decreased macrophage function. The study, co-authored by Netusha Thevaranjan and Alicja Puchta, uses multiple mouse models to show that age-associated inflammation is driven by an aging microbiota, and reducing TNF levels can reverse both age-related microbial changes and inflammation. This has important implications regarding how maintaining a healthy microbiome and reversing age-related microbial changes can help improve our health as we grow older. Read the full story here.
In the article entitled “Innate Immune Cytokines, Fibroblast Phenotypes, and Regulation of Extracellular Matrix in Lung,” Carl Richards, PhD, McMaster University, Hamilton, Canada, examines the scientific evidence suggesting that cytokines stimulated by the innate immune system can directly control fibroblast behavior. Fibroblasts are major contributors to extracellular remodeling and regulate the accumulation of inflammatory cells, which can lead to chronic inflammation and ultimately to organ dysfunction. Dr. Richards discusses the potential of metabolic changes, age, and epigenetic mechanisms to affect the activity of fibroblasts and immune system cell populations through impact on cytokine-mediated signaling pathways.
“Dr. Richards has made major contributions to our understanding of cytokine mediated effects on inflammatory disorders mediated through interactions between the immune system and resident fibroblasts,” says Journal of Interferon & Cytokine Research Co-Editor-in-Chief Thomas Hamilton, Department of Immunology, Cleveland Clinic Foundation, Cleveland, OH. “This review provides a highly relevant discussion of these issues and is particularly timely as our ability to use this knowledge is enabling new therapeutic strategies to treat inflammation-related chronic disease.”
The annual Medical Sciences Research Day took place on January 25th and several MIRC trainees were selected to feature their work at this day-long research event. From oral talks, to poster presentations, students did a great job representing MIRC and their respective research groups. Lisa Newhook (Bramson), Joanne Hammill (Bramson), Sara Dizzell (Kaushic) and Puja Bagri (Kaushic) all gave excellent oral presentations, while Donald Basin (Wan), Jessica Breznik (Bowdish), Grace Teskey (Bowdish), Anisha Dubey (Richards) and Danielle Vitali (Kaushic) did an exceptional job with their poster presentations. Congratulations to all presenters for a job well done! Just a reminder, all MIRC graduate students are welcome to submit abstracts for the upcoming Health Sciences Research Plenary, which will be taking place in May.