Pulmonary tuberculosis (TB) caused by Mycobacterium Tuberculosis, is one of the leading causes of global morbidity and mortality, and one of the primary reasons for the deathly nature of this infection is the absence of an effective vaccine. Although there are numerous candidate TB vaccines being tested, the ability of these vaccines to improve protection by inducing clinically relevant protective T cell responses is largely unknown until the completion of expensive efficacy trails. As such, not only is there an urgent need to develop effective vaccination strategies, there is also a pressing need to develop alternative approaches to evaluate the protective potential of vaccine candidates. This can save a lot of valuable time and money. Interestingly, Dr. Zhou Xing’s lab has developed a systematic immunological approach to investigate the protective potential of a novel TB vaccine. In the newly published study directed by Dr. Mathy Jeyanathan, PBMC’s cryopreserved from healthy adults who had been vaccinated intramuscularly with a novel TB vaccine in a previous phase I study were used to screen for likely dominant T cell epitopes following vaccination. Next, Jeyanthan et al. expanded antigen-specific memory T cell lines to identify CD4 and CD8 memory T cell epitopes, and found that immunization with the vaccine in question resulted in the generation of a memory T cell repertoire capable of recognizing multiple epitopes. Furthermore, the epitope-specific memory T cells were polyfunctional and cytotoxic, and able to suppress mycobacterial growth in infected cells. Based on this approach, the study recommended that the candidate TB vaccine in question should undergo further development. Most importantly, Jeyanthan et al. have created an approach that can be incorporated into future early TB vaccine trails and can be used to greatly assist in TB vaccine development. Read more here.
IL-33, known to play a role in both innate and adaptive immune responses, has been suggested to be involved in inflammatory lung disease, as IL-33 influences Th2-skewed immune functions in allergic responses. Evidently, elevated levels of IL-33 are found in mouse models of allergic airway disease and in chronic human lung conditions such as severe asthma. Similarly, the gp130 cytokine Oncostatin M (OSM) is also known to be elevated in cases of severe asthma. However, the link between OSM and IL-33 remained largely unknown until a recent study out of Dr. Carl Richard’s lab suggesting a novel OSM-IL-33 axis in lung tissue cells. Led by Dr. Fernando Botelho, the study provides evidence for a novel method of IL-33 regulation in murine lung epithelial cells mediated by OSM. Using an in vivo mouse model and cell-culture techniques, they found that transient overexpression of OSM resulted in significantly increased induction of IL-33 in the lung, specifically in alveolar epithelial cells. In addition, IL-33 induction was associated with the activation of STAT3 and inhibition of STAT3 reduced IL-33 levels, suggesting a role for STAT3 activation in OSM-mediated regulation of IL-33. This study demonstrates a new role for OSM as a potent inducer of IL-33 in mouse lung epithelial cells, suggesting an additional mechanism for IL-33 regulation in innate immunity and pulmonary pathology. Read more here.
The 2016 Faculty of Health Sciences (FHS) Research Plenary was held from May 17-19th and showcased the work of several MIRC students and postdoctoral fellows via oral and poster presentations. Several MIRC trainees were selected for special awards. The following students were awarded Excellence in Poster Presentations: Sara Dizzell, Anisha Dubey, Dessi Loukov and Danielle Vitali. In addition, Kyle Novakowski was awarded for Outstanding Oral Presentation.
Other awards were also presented at the reception, recognizing the excellent work and outstanding achievements of MIRC trainees.
Faculty of Health Sciences Graduate Programs Outstanding Achievement Award
Faculty of Health Science Graduate Programs Outstanding Thesis Awards
Faculty of Health Sciences Graduate Programs Outstanding Excellence Awards
2015-2016 External and Internal Award Holders
Kaushal Baid (Mitacs Globalink Graduate Fellowship)
Michael Dorrington (Canadian Lung Association)
Joanne Hammill (Canadian Breast Cancer Foundation doctoral award)
David Hare (NSERC PGS-D3)
Joshua Koenig (CIHR CGS-M)
Amanda Lee (CIHR Vanier)
Joshua McGrath (Firestone Institute for Respiratory Health Graduate Students Scholarship)
Aveshni Naidoo (CGS-D Banting)
Kyle Novakoswski (Ontario Graduate Scholarship)
Pat Schenck (CIHR CGSD)
Tarandeep Singh (Ontario Graduate Scholarship)
Netusha Thevaranjan (The Michael Kamin Hart Memorial Scholarship)
Congratulations to all of the MIRC award winners!
Join us today to watch our very own, Dr. Dawn Bowdish, as she gives a presentation on inflammation, infections and the immune system on September 10th starting at 8 pm in EAC. The presentation is sponsored by Hamilton Association for the Advancement of Literature, Science and Art.
HSV-2 is one of the most dominant sexually transmitted infection (STI) worldwide, with global estimates of approximately 530 million individuals who are positive for HSV-2. Rate of infection is higher in women, however, the cause for increased susceptibility has not been established. It has been shown that the hormonal microenvironment may be playing a role, as hormone treatment in animal models has shown to differentially prime immune responses to HSV-2. A recent study examining the role of estradiol in HSV-2 infection, led by MIRC graduate Varun Anipindi from Dr. Charu Kaushic’s lab, was published in PLoS Pathogens. The study showed, for the first time, a mechanism to describe how estradiol, a female sex hormone present during the menstrual cycle and found in oral contraceptives, can protect against sexually transmitted viral infections. Using a mouse model of HSV-2 infection, Anipindi and collegues showed that estradiol primes dendritic cells in the vaginal tract to induce a Th17 response, which coincides with an increase in anti-viral Th1 responses. This pathway has important implications for addressing if some hormonal contraceptives may be better than others for women who are at higher risk for acquiring STIs. In addition, “We hope this raises awareness about the importance of vaccines administered by the mucosal route, and how this strategy can induce better protection,” says lead author Dr. Varun Anipindi. The study was highlighted as the Featured Research Article by PLoS Pathogens, selected by the Editors-in-Chief as being “a high-quality research article that is of particular importance and relevance to the pathogens community and general public”. Congratulations to Dr. Varun Anipindi and Dr. Charu Kaushic! Read More.
Congratulations to Matthew Miller for being awarded the 2015 - 2016 CIHR New Investigator Award!
Sex hormones, estrogen and progesterone, are known to influence the type of immune response initiated in response to infection, including dendritic cell (DC) development and function. A study published by past MIRC member Dr. Fangming Xiu from Dr. Charu Kaushic’s group examined how a range of physiological concentrations of female sex hormones estradiol and progesterone, as well as combinations of both, effected the differentiation and function of murine bone marrow derived dendritic cells (BMDC). Estradiol was shown to enhance DC differentiation, while progesterone did the opposite at high concentrations and inhibited DC differentiation. When combined, higher concentrations of progesterone, similar to levels seen during pregnancy, reversed the effect or estradiol. Similarly, antigen uptake was decreased and production of pro-inflammatory cytokines by DCs was increased in the presence of estradiol, while these effects were reversed by high concentrations of progesterone. This study showed the unique effects of estradiol and progesterone on differentiation and functions of BMDCs, and how the two hormones interact to influence DC development and function. This suggests that DC functions may differ depending on the stage of the menstrual cycle or pregnancy, and provides a better understanding of hormone-mediated regulation of DC differentiation and function. Read More.
Exciting news coming from the Kaushic Lab, where post-doctoral fellow Dr. Jocelyn Wessels was recently awarded the prestigious Ontario Women’s Health Fellowship. The award, funded in 2001 by the Ontario Ministry of Health and Long-Term Care, recognizes a distinguished group of Ontario scholars who are working to improve women’s health through research focusing on issues such as contraception, breast cancer, and health during pregnancy. The award hopes to support scholars in their efforts to create new knowledge about women’s health, and to help develop more effective health services and products for women. MIRC member Dr. Wessels was one of only two post-doctoral fellows to receive the award, which includes a $50,000 fellowship and an additional $5000 for research. Her research focuses on how female sex hormones found in contraceptives affect vaginal health and susceptibility to sexually transmitted infections, such as HIV. Specially, Dr. Wessels’ research will investigate how Depo-Provera, a progestin-based contraceptive, affects healthy bacteria within the vaginal tract which protect against infections, and whether these changes make women more susceptible to HIV. Read more about the award here, and congratulations to Dr. Wessels!
Idiopathic pulmonary fibrosis (IPF) is an irreversible progressive fibrotic disorder. The activation of the unfolded protein response (UPR) has been found to be critical in the differentiation of different cell types from quiescent states to more active forms. UPR may also initiate apoptotic cell death by upregulating the C/EBP homologous protein (CHOP). Both endoplasmic reticulum stress, along with the unfolded protein response (UPR), have been associated with fibrotic lung disease, however the mechanism remains unknown. A recent study published by PhD student Ehab Ayaub in Dr. Kjetil Aski’s lab demonstrated that fibrotic response to bleomycin is dependent on events mediated by GRP78, the main UPR regulator. Furthermore, they suggested that macrophage polarization and apoptosis may play a role. The study used an experimental mouse model of lung injury and fibrosis to study the role of GRP78. GRP78 +/- mice were protected from bleomycin-induced fibrosis, with reduced number of lung macrophages. Conversely, Chop -/- mice showed opposite outcomes. In addition, GRP78- and CHOP-mediated macrophage apoptosis was protective against bleomycin-induced fibrosis, demonstrating that macrophages play an important role in fibrosis. This study provides better understanding of the mechanism involved in the development of bleomycin-mediated fibrosis, and the findings have implications in the development of novel therapies. Read More.
Congratulations to PhD candidate David Hare from Dr. Karen Mossman’s lab, who was recently awarded the Medical Sciences Impact Award. The Impact Award acknowledges graduate students who have demonstrated excellence in research and whose work has been published in a highly meritorious first-authored scientific paper. It is presented to one student from each research stream in the Medical Sciences program on a yearly basis, and David Hare is this year’s winner from the Infection and Immunity stream. David recently published in the Journal of Virology, reporting on the role of cytosolic receptors and their ability to recognize genomes within incoming virus particles prior to virus replication. Congratulations David! Read More.
MIRC hosted the 3rd Annual D. Y. E. Perey Symposium on June 7, 2016 at McMaster Innovation Park. This year’s day-long symposium highlighted the work being done by MIRC trainees, as they presented their research in the form of 3 minute speed talks, and oral and poster presentation. In addition, there were two keynote addresses by top scientists Dr. Ankur Singh and Dr. Benjamin tenOever. Cornell University’s Dr. Ankur Singh started off the day by delivering a riveting talk on using novel micro-nano-bioengineering strategies to develop therapeutics for cancers and vaccines for infectious disease. The Perey Symposium was closed off by Dr. Benjamin tenOever from Mount Sinai, who impressed attendees with his talk on the study of microRNAs and their role in the cellular response to viral infections.
The event ended with a reception where awards were presented in various categories. Sara Dizzell, a Masters student in Dr. Charu Kaushic’s lab, was awarded for her poster on understanding the effect of sex hormones and lactobacilli on genital epithelial cell barrier functions in the presence and absence of HIV-1. Danya Thayaparan, a Masters student in Dr. Martin Stampfli’s group, was awarded the lay person award for her poster on characterizing the development of cardiovascular pathologies in cigarette smoke-exposed apolipoprotein E-deficient mice. The award for the 3 minute thesis speed talk went to PhD student Jewel Imani in Dr. Mark Larche’s lab, for his effective presentation on the role of donor derived complement protein C5 in the development of pulmonary manifestations in chronic graft vs. host disease in mice.
Special thanks goes out to the planning committee composed of MIRC trainees Ksenia Bezverbnaya, David Hare, Josh McGrath, Ken Mwawasi, and Dessi Loukov, who did an exceptional job organizing the entire symposium.