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.
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.
Yung Lee, an undergraduate student in Dr. Charu Kaushic’s lab, was recently 1 of 3 second year undergraduate students awarded the Wilson Leadership Scholar Award. The Wilson Scholar program “recognizes Canada’s promising undergraduate students, cultivating their untapped potential and preparing them to serve as the nation’s next generation of leaders.” The award, which includes $50, 000 to cover educational expenses, along with admission to a leadership development program, is one of the highest valued undergraduate scholarships in Canada. The Kaushic lab is extremely proud of Yung’s continued excellence and achievements!
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.
Congratulations to Yung Lee from Dr. Charu Kaushic’s lab and Jason Fan from Dr. Dawn Bowdish’s lab for being awarded the highly competitive IIDR Summer Student Fellowship. Yung and Jason are two of just ten undergraduate students selected for this fellowship, which is designed to support students working in the labs of IIDR members during their summer practicum.
Streptococcus pneumoniae is a leading cause of invasive bacterial infections. Although cigarette smoke is a risk factor known to be involved in the development of invasive pneumococcal disease, the underlying mechanism remains to be determined, primarily due to the lack of a clinically relevant animal model. A study published by PhD student Pamela Shen from Dr. Martin Stampfli’s lab, reported a novel model of nasal pneumococcal colonization in cigarette smoke-exposed mice, which was used to demonstrate, for the first time, that cigarette smoke predisposes mice to invasive pneumococcal infection and mortality. Mechanistically, the study showed that cigarette smoke impaired the response to S. pneumoniae by suppressing the expression of nasal inflammatory mediators, such as neutrophil-recruiting chemokines. Furthermore, they reported that the effects of cigarette smoke might be reversible, as smoking cessation during nasal colonization fully rescued mice from disease. Considering the fact that over 1 billion individuals smoke worldwide, this suggests that a considerable proportion of the global population is at increased risk, and the findings from this study may help guide future efforts to reduce the incidence of invasive pneumococcal disease. Read More
PhD student Dessi Loukov in the lab of Dr. Dawn Bowdish, recently published a study showing that splenomegaly in old mice is a result of extramedullary hematopoiesis, and that this increased monopoiesis is driven by age-associated increase in TNF. The study compared changes in the microarchitecture and composition of the spleen in old and young mice and found that in old mice, there was an increase in the size and cellularity of the red pulp (the site of hematopoiesis of myeloid precursors). To study the role of TNF in the development of extramedullary hematopoiesis, they used TNF KO mice and found that these mice did not have increased extramedullary monopoiesis. Furthermore, they demonstrated that increased splenic myelopoiesis was a result of the aging microenvironment. This work suggests that strategies which aim to decrease the inflammatory microenvironment that comes with aging, would be effective in reducing inflammatory diseases propagated by cells of the myeloid lineage. Read More
Dr. Jonathan Bramson’s group has recently received additional financial support from Mark Samuel and Kevin Sanford, both family members connected to the Samuel Family Foundation, to help bring their technology in cancer therapy from the lab into development for clinical use. The Samuel Family Foundation was founded in 2014, where $500, 000 were donated in an effort to help researchers at MIRC to develop a personalized immunotherapy cancer treatment. Just this month, the foundation has added another $250, 000, and Mark Samuel and Kevin Sanford have given an additional $200, 000 towards this investment in science. The Samuel Family Foundation supports work which is being carried out in the laboratory of Dr. Jonathan Bramson, and part of the funds also support immunological research trainees. Currently, Ksenia Bezverbnaya and Ken Mwawasi, MIRC trainees in the Bramson lab, are the two Samuel Family Scholars, however, more will be recruited. Family members associated with the foundation hope the gift will support bringing the early developmental work from the lab towards use in a clinical setting.
Colonization of Streptococcus pneumoniae within the upper respiratory tract (URT) of elderly individuals is a major concern, as it often results in the development of pneumonia, which can be deadly in this population. A study published by MIRC Masters’ student Netusha Thevaranjan, under the supervision of Dr. Dawn Bowdish, examined how aging can change the composition of the respiratory microbial community and consequently, impact bacterial colonization. Using a mouse model of pneumococcal colonization, the study characterized the composition of the URT microbiota in young, middle-aged, and old mice in both the naïve state, and throughout the course of nasopharyngeal colonization with S. pneumoniae. It was shown that the composition of the URT microbiota differs with age, and that colonization with S. pneumoniae in older mice disrupted pre-existing microbial communities.
Furthermore, the study demonstrated that there were several interspecies interactions between S. pneumoniae and resident microbes. In particular, Streptococcus interacted competitively with Staphylococcus and synergistically with Haemophilus. This work provides insight into how aging influences bacterial colonization, and understanding the relationship between these two factors can help create strategies to protect the elderly from age-associated infections and disease. Read More
A video produced by MIRC undergraduate student Yung Lee on Macrophage Evolution, featuring Dr. Dawn Bowdish and her lab, won a runner-up prize in the NSERC’s Science, Action! Video Contest. Congratulations to Yung and the Bowdish group!
Watch the video here!
Recently, a major discovery has been uncovered with the collaboration of Brian Lichty and Yonghong Wan from McMaster’s DeGroote School of Medicine. The study can lead to the development of vaccines for viruses like herpes, a common cold or even cancer. This research explains how our immune system detects a viral infection. Licthy have stated: "If the key immune system component identified in these studies is not triggered, then vaccination fails".
The group have focused in studying the cytosolic dna-mediated activation of the transcription factor IRF3 which is a key event in host antiviral responses. The findings have revealed a fundamental regulatory mechanism for the activation of IRF3 in the cytosolic DNA pathway. Nonetheless, the amazing effort by the lead author, Dr. Fuan Wang have revealed a groundbreaking story that impacts everyone who are infected by a virus, receiving a vaccination or fighting cancer
This study was recently published in "Nature Immunology". Further details can be found here.