November is Lung Month! The Bowdish lab gets involved with the Breathing As One campaign.


Research in Lung health is not nearly as well funded as it should be considering the toll it takes on patients and our healthcare system. That’s why the Bowdish lab is involved in the Lung Association’s Breathing as One campaign to raise money for lung research. Click on the picture to read the insert that was delivered in a number of newspapers (including our own Hamilton Spectator) to launch the campaign.Lung Association Breathing as One

The Bowdish lab is on a roll!

This past month has been very productive in the Bowdish laboratory, with many triumphs achieved by it’s industrious members.

Firstly, a big congratulation goes to Kyle Novakowski, the Bowdish 2013-10-17 23.42.39lab’s newest PhD student. Following a lot of hard work, determination and great dedication to his Masters project, Kyle successfully passed his transfer exam on July 7 and has officially begun his seemingly endless exciting pursuit for a PhD. Good luck to Kyle in continuing his interesting investigation on the regulation and function of MARCO!

 

Dessi Loukov presents her undergraduate work in the Bowdish lab at the 1st annual Perey Symposium, convinces everyone she's a senior PhD student and brings home the Faculty choice award for best speed poster presentation.

Dessi Loukov presents her undergraduate work in the Bowdish lab at the 1st annual Perey Symposium, convinces everyone she’s a senior PhD student and brings home the Faculty choice award for best speed poster presentation.

Next up is Dessi Loukov, who is currently an undergraduate but come September will be the Bowdish lab’s 4th PhD student. At the 1st annual MIRC Perey Symposium held on June 19, Dessi impressed faculty and trainees with her educational and enthusiastic speed poster presentation on modulating the immune system to potentially reverse age-associated inflammation. Dessi was awarded a travel award as a result of her superb presentation skills. Kudos also to Fan Fei (PhD candidate) and Avee Naidoo (MSc candidate) who gave excellent speed poster talks and Dr. Chris Verschoor who gave an excellent oral presentation.  Who knew that research in inflammation could be so exciting? The Bowdish lab, that’s who!

One PhD candidate who deserves great recognition for his recent successes is Mike Dorrington. Not only was Mike awarded with a prestigious and well-deserved Canadian Lung Association & Canadian Thoracic Studentship, but he additionally achieved received The Ruth and Wilson Tafts Prize for Immunology for having the best paper published in a peer-reviewed journal in 2013. Geez Mike, save some awards for the rest of us. These awards will be used to further fund his fascinating work on the role of macrophages – clearly, the best cell around – in recognition and clearance of Streptococcus pneumoniae in the upper respiratory tract. Congratulations Mike!

At the celebration of Mike's first first author publication. Although Dawn is mostly happy for Mike, she is also slightly nervous that she might be about to lose an eye when the champagne is opened.

At the celebration of Mike’s first first author publication. Although Dawn is mostly happy for Mike, she is also slightly nervous that she might be about to lose an eye when the champagne is opened.

Then, there’s Dr. Chris Verschoor, the lab’s most productive and well-rounded member. Chris’ paper entitled, “Alterations to the frequency and function of peripheral blood monocytes and associations with chronic disease in the advanced-age, frail elderly“, was recently accepted into the PLoS one. If you’re interested in changes in monocyte populations with age – I mean, who isn’t? – keep a look out for Chris’ article in the next issue of PLoS one . Way to go Chris on this well-deserved publication!

Chris-sm

 

<- Manuscipt accepted = happy post-doc.

 

 

And last, but definitely not least, the lab takes great pleasure in congratulating our passionate leader, Dr. Dawn Bowdish, who has been awarded tenure and a promotion to Associate Professor effective as of July 1, 2014. This accomplishment is a fitting acknowledgement of Dawn’s exceptional work, devotion and academic contributions to research in the field of macrophage biology. In addition to her promotion and tenure, Dawn recently received a Best Teacher Award in the Department of Pathology for excellence in undergraduate teaching and graduate supervision. Well-done Dawn!

Dawn receives the Pathology & Molecular Medicine Department's best teacher award for her undergraduate and graduate supervision. Dr. Murray Potter, the education co-ordinator and Dr. Fiona Smaill, the chair, present her with the award.

Dawn receives the Pathology & Molecular Medicine Department’s best teacher award for her undergraduate and graduate supervision. Dr. Murray Potter, the education co-ordinator and Dr. Fiona Smaill, the chair, present her with the award.

Congratulations Bowdish lab on our successes!

Way to kill it, like young macrophages on pneumo 😉

Funding from the province of Ontario supports two new graduate students!

Bowdish lab receives funding from the province of  Ontario to train two new graduate students! Avee Naidoo (MSc) and Dessi Loukov, who will be starting a PhD in Sept 2013,  will be studying how age-associated inflammation predisposes older adults to pneumonia.

For full details on the award for Dawn’s proposal “Interplay between inflammation and impaired anti-bacterial immunity in the elderly.”
http://iidr.mcmaster.ca/IIDR-news/ERAs-2014.html#.UzXGj_ldWSo

Dessi Loukov, pictured here pushing back the boundaries of science.

Dessi Loukov, pictured here pushing back the boundaries of science.

Aveshni Naidoo, MSc sits beside the coolest jack-o'-lantern ever.

Aveshni Naidoo, MSc sits beside the coolest jack-o’-lantern ever.

Puchta et al. Characterization of inflammatory responses during intranasal colonization with Streptococcus pneumoniae. Vis Exp. 2014 Jan 17;(83):e50490. doi: 10.3791/50490.

Puchta A, Verschoor CP, Thurn T, Bowdish DMCharacterization of inflammatory responses during intranasal colonization with Streptococcus pneumoniae. J Vis Exp. 2014 Jan 17;(83):e50490. doi: 10.3791/50490.

MARCO is required for TLR2- and NOD2-mediated resonses to Streptococcus pneumoniae and clearance of pneumococcal colonization in the murine nasopharnyx. 2013. Dorrington et al. J. Immunol.

Click image for .pdf of paper.

Dorrington JI

Despite having multiple vaccines against Streptococcus pneumoniae available today, over a million people die each year due to pneumococcal infections. Mike Dorrington, a Ph.D. candidate in the Bowdish lab, is attempting to understand how to produce better vaccines by gaining a better grasp on how the immune system fights these bacteria. Mike has recently published a manuscript entitled “MARCO is required for TLR2- and NOD2-mediated responses to Streptococcus pneumoniae and clearance of pneumococcal colonization in the murine nasopharynx” in the Journal of Immunology. Mike’s work focuses on the importance of macrophage scavenger receptors in immune protection against S. pneumoniae, the most common cause of bacterial pneumonia. This manuscript provides us with evidence that Macrophage Receptor with Collagenous structure (MARCO), a class A scavenger receptor, plays an integral role in establishing and maintaining the appropriate innate immune response to the bacteria in its preferred niche, the nasal passage.

     S. pneumoniae is a very common pathogen that causes fatal disease in children under the age of 5 (where it often causes meningitis) and adults over the age of 65 (where it most often presents in pneumonia). Before infectious disease occurs, bacteria colonize the nasal passages of individuals where they replicate. If the bacteria are able to persist for long enough, they will then move to the lungs, blood, or meninges and cause potentially life-threatening disease. It has previously been shown that the clearance of the bacteria from the nasal passages was dependent on an influx of macrophages to the site. These cells are able to internalize and kill the bacteria efficiently. MARCO is expressed by these active macrophages and has been shown to play a role in the recognition of the bacteria.

Mike’s work shows that mice who lack MARCO expression are unable to clear bacterial colonization in a timely fashion. This is due to a decrease in a number of innate immune functions. First, MARCO-deficient mice have significantly less recruitment of innate immune cells such as neutrophils and macrophages to the site of colonization. Without these cells, the bacteria are free to thrive and replicate in the nasal passage, increasing the chance that they will travel to further tissues and cause disease. MARCO-deficient mice also present with less inflammation than they’re wild-type counterparts, as seen by a paucity of pro-inflammatory cytokines and chemokines including, surprisingly, type I interferons (cytokines associated with antiviral immunity). These data are supported by experiments performed in vitro using macrophage populations from MARCO-deficient and wild-type mice. When these cells are stimulated with S. pneumoniae, the MARCO-deficient macrophages produce less cytokines and chemokines. These cells are also less able to internalize the bacteria, a key step in the destruction of the pathogens.

A potentially ground-breaking finding that comes from Mike’s work is that MARCO is able to modulate the activity of other important innate immune receptors. Mike has shown that NF-kB activation in S. pneumoniae-stimulated cells expressing MARCO along with TLR2 and its co-receptor CD14 is much higher than cells not expressing MARCO. This is also true of cells expressing MARCO as well as NOD2 when compared to those expressing just NOD2. As NF-kB is a central regulator of immune function, this represents a very important step in our understanding of antibacterial innate immune responses in the nose.

Mike’s work on MARCO will continue as he attempts to uncover the mechanism by which MARCO increases NF-kB activation by these other receptors. It is his hope to be able to apply these advances in the basic science to vaccine development in order to generate an effective strain-independent vaccine against S. pneumoniae infection.

Dr. Dawn Bowdish receives a research award from the Ontario Lung Association and Pfizer Canada (and gets to attend a swanky event to receive it!)

Dawn was thrilled to attend the annual Breathe! gala event hosted as a fundraising event for the Ontario Lung Association to receive an award donated by Pfizer Canada and administered by the Ontario Lung association. Not only did it give her a chance to dress up and go out (a rare event!) for an evening of good food and drink but she was inspired to meet some of the spokespeople of the event, including Helene Campbell, who spent her time waiting for a double lung transplant starting an immensely successful social media campaign to increase organ donation, Ann Marie Cerato, a lung cancer survivor and Kayla Baker, a young sarcoidosis patient on a waiting list for a lung transplant. Not only was it inspiring to meet these brave, bold heroes but it was humbling to be in a room full of people whose lives were all touched by the research funded by the Ontario Lung Association.

Dawn standing beside the real heros of the event, Helene Campbell, double lung transplant recipient and idiopathic fibrosis patient, Ann Marie Cerato, lung cancer survivor and Kayla Baker sarcoidosis patient waiting for a lung transplant.

So what did Dawn win her award for? You can take a look at the YouTube video here or read on…

President of Pfizer Canada, John Helou (L) and Dr. John Granton, chair elect of the Ontario Lung Association (R) present Dr. Dawn Bowdish with the OLA-Pfizer Research Award.

Description of research funded by the Ontario Lung Association-Pfizer Ca award

neumonia is the sixth most common cause of death in Canada.  The incidence of pneumonia rises steeply in individuals over the age of 65 years and approximately 90% of deaths due to pneumonia occur in the elderly (>65 yrs).  Current prevention strategies are inadequate as the vaccination does not prevent pneumonia in most elderly individuals. Recent research from the Bowdish lab demonstrates that one of the reasons the elderly are so susceptible to pneumonia is that their immune systems cannot control the bacteria that normally live in our sinuses. The immune systems of healthy adults can keep the bacteria (Streptococcus pneumoniae) in the sinuses (“pneumococcal carriage”) and eventually clear them, but for reasons we don’t understand, the immune systems of the elderly cannot and as a result the bacteria break through the immune barriers of the sinuses and spread to the lungs, which results in pneumonia.

Although most people think that the elderly get sick because their immune systems “just don’t work”, in fact our data demonstrate that they recruit more white blood cells to the sinuses when they encounter the bacteria that cause pneumonia than healthy adults. Even though they have more white blood cells in the sinuses they don’t seem to be as good at recognizing and killing bacteria. Our goal is to figure out why they have overactive recruitment of white blood cells and why they aren’t as good at killing bacteria as white blood cells from healthy adults.

We have developed what we believe to be the world’s only Aged mouse model of colonization by pneumonia causing bacteria. This allows us to study how the immune system responds to the presence of bacteria in the sinuses in real-time. In addition we have a bank of white blood cells from adults and elderly patients that allow us to confirm the importance of our mouse studies in people.

Hospitalizations and deaths due to pneumonia are unacceptably high in the elderly. This is likely because vaccination of the elderly only does not protect against pneumonia. New methods for preventing infection are urgently required. Our recent data demonstrates that containment and clearance of pneumococcal carriage is impaired in age and results in increased susceptibility to pneumonia; however the mechanisms by which immune control of the sinuses fails remain to be discovered. Prevention of colonization of the sinuses will therefore be essential for control of pneumonia in this population. In order to develop novel therapeutic interventions for the elderly it will be necessary to discover the mechanisms by which bacterial recognition, killing are impaired in the sinuses.

Helene Campbell, conceivably, the most charming woman alive and the recipient of a double lung transplant, leads a dance with the Hon Deborah Mathews (MPP). The music failed so I held my iPod up to the Mike and we played Metric's "Sympathy".

Mike Dorrington (PhD candidate) discovers that MARCO is required for recognition and removal of S. pneumoniae in the sinuses.

Despite having multiple vaccines against Streptococcus pneumoniae available today, over a million people die each year due to pneumococcal infections. Mike Dorrington, a Ph.D. candidate in the Bowdish lab, is attempting to understand how to produce better vaccines by gaining a better grasp on how the immune system fights these bacteria. Mike has recently published a manuscript entitled “MARCO is required for TLR2- and NOD2-mediated responses to Streptococcus pneumoniae and clearance of pneumococcal colonization in the murine nasopharynx” in the Journal of Immunology. Mike’s work focuses on the importance of macrophage scavenger receptors in immune protection against S. pneumoniae, the most common cause of bacterial pneumonia. This manuscript provides us with evidence that Macrophage Receptor with Collagenous structure (MARCO), a class A scavenger receptor, plays an integral role in establishing and maintaining the appropriate innate immune response to the bacteria in its preferred niche, the nasal passage.

At the celebration of Mike’s first first author publication. Although Dawn is mostly happy for Mike, she is also slightly nervous that she might be about to lose an eye when the champagne is opened.

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

     S. pneumoniae is a very common pathogen that causes fatal disease in children under the age of 5 (where it often causes meningitis) and adults over the age of 65 (where it most often presents in pneumonia). Before infectious disease occurs, bacteria colonize the nasal passages of individuals where they replicate. If the bacteria are able to persist for long enough, they will then move to the lungs, blood, or meninges and cause potentially life-threatening disease. It has previously been shown that the clearance of the bacteria from the nasal passages was dependent on an influx of macrophages to the site. These cells are able to internalize and kill the bacteria efficiently. MARCO is expressed by these active macrophages and has been shown to play a role in the recognition of the bacteria.

Mike’s work shows that mice who lack MARCO expression are unable to clear bacterial colonization in a timely fashion. This is due to a decrease in a number of innate immune functions. First, MARCO-deficient mice have significantly less recruitment of innate immune cells such as neutrophils and macrophages to the site of colonization. Without these cells, the bacteria are free to thrive and replicate in the nasal passage, increasing the chance that they will travel to further tissues and cause disease. MARCO-deficient mice also present with less inflammation than they’re wild-type counterparts, as seen by a paucity of pro-inflammatory cytokines and chemokines including, surprisingly, type I interferons (cytokines associated with antiviral immunity). These data are supported by experiments performed in vitro using macrophage populations from MARCO-deficient and wild-type mice. When these cells are stimulated with S. pneumoniae, the MARCO-deficient macrophages produce less cytokines and chemokines. These cells are also less able to internalize the bacteria, a key step in the destruction of the pathogens.

A potentially ground-breaking finding that comes from Mike’s work is that MARCO is able to modulate the activity of other important innate immune receptors. Mike has shown that NF-kB activation in S. pneumoniae-stimulated cells expressing MARCO along with TLR2 and its co-receptor CD14 is much higher than cells not expressing MARCO. This is also true of cells expressing MARCO as well as NOD2 when compared to those expressing just NOD2. As NF-kB is a central regulator of immune function, this represents a very important step in our understanding of antibacterial innate immune responses in the nose.

Mike’s work on MARCO will continue as he attempts to uncover the mechanism by which MARCO increases NF-kB activation by these other receptors. It is his hope to be able to apply these advances in the basic science to vaccine development in order to generate an effective strain-independent vaccine against S. pneumoniae infection.

Dr. Bowdish receives a CIHR Operating Grant from the Institute of Aging.

Dr. Bowdish’s grant, titled Macrophage function changes and contributes to susceptibility to infectious disease, was awarded $730,124 from the CIHR Institute of Aging.  This new grant will examine age-related changes in monocytes and macrophages to better understand aspects of aging that increase suceptibility to Streptococcus pneumoniae infection. This grant will likely allow Dr. Bowdish to hire a new post-doctoral fellow and graduate student. Interested applicants should consult the FAQ page.

MIRC scientists were highly successful in this recent round of CIHR funding (especially considering the low rates of funding!). To see who else got funded, click here.

 

 

Dr. Chris Verschoor’s award winning work on pneumonia in the elderly profiled.

To read about the work which won him the prestigious M.G. DeGroote post-doctoral fellowship, see this article…http://fhs.mcmaster.ca/main/news/news_2012/mgdfa_recipients_2011.html

Dr. Verschoor is tackling an issue of grave importance to Canada’s aging population – the high toll of infectious disease. As an example, 90% of pneumonia deaths in Canada occur in the elderly at tremendous cost to our health care system. Pneumonia is often the result of a period of decreased mobility (e.g. hip fracture and hospital stay) and the beginning of a decline in health. Preventing infections would keep the elderly healthy for longer and provide increased independence, decrease the cost of care and result in longer, happier lives.