Rajiv’s SPRINT project – completed!

Two years ago I (Rajiv) went to the 2016 MS summer school in Vancouver Canada to start my endMS Scholar Program for Researchers IN Training (SPRINT) project. In this program, three trainees from different fields of research are brought together to work on one interdisciplinary project over the course of a year. My project was supervised by Dr. Ghasemlou from Queens University and focused on reviewing the literature surrounding circadian rhythms (how biological functions are altered over the course of a day/year) and their effects on MS pathology and psychosocial outcomes.

Overall, we found that the rhythmic release of hormones associated with circadian rhythms, melatonin and cortisol, are either blunted or amplified, respectively, in MS patients. These hormones are known to influence immune responses and are likely influencing MS pathology and may also contribute to psychosocial aspects of MS including fatigue, depression, and disability. Lastly, all of the currently approved MS drugs target some portion of the immune system that has an associated circadian rhythm. Thus, there is untapped potential in considering whether the timing of administration of our current drugs could be used to further amplify their efficacy.

This work was recently accepted for publication in the Journal of Neuroscience and Biobehavioral Reviews. Overall, the SPRINT experience is rewarding and is definitely worth pursing for those who are motivated to work on a project with people outside of their own field. This is also a good opportunity to thank Dr. Nader Ghasemlou and his lab for their support in producing this publication as well as the other members of the SPRINT team, Dr. Kelvin Poon and Elisea De Somma as this could not have been completed without you!

Working with Others

We had a chance to collaborate with Dr. Luc Vallières and his team at the Université Laval in a study that was recently published in the Journal of Clinical Investigation Insight. In the paper, Hawkins et. al. shows that during central nervous system (CNS) autoimmunity, a population of neutrophils gains access to the inflamed CNS. Interestingly, these CNS neutrophils acquire a very un-neutrophil like property: the ability to acquire and present antigens to T and B cells – something normally performed by very different kinds of immune cells.

We contributed to this study through our ongoing work to develop and characterize mouse models of CNS autoimmunity that incorporate B cells in the disease process. We found extensive neutrophil invasion of the CNS in one of these B cell-dependent models of CNS autoimmunity induced using a modified MOG protein that we developed. By using this B cell-dependent model, Hawkins et. al. showed that deletion of a protease (ASPRV1), which is highly expressed in CNS neutrophils, leads to a significant decrease in the severity of CNS autoimmunity.

Overall this has been, and will continue to be, a productive collaboration that has taught us a great deal about how neutrophils contribute to CNS autoimmunity but also identifies a novel role for neutrophils in the immune response that remains unstudied.

2017 J Allyn Taylor International Prize in Medicine recognizes Multiple Sclerosis research

Last week the Robarts Research Institute awarded the 2017 J. Allyn Taylor International Prize in Medicine to Dr. V. Wee Yong from the University of Calgary. Every year a theme is chosen for the prize, and this year the theme was Multiple Sclerosis. I was honored to participate as a member of the organizing committee and particularly pleased to see Dr. Yong receive the prize.

 Dr. Yong (far right beside Steve) participating in a public panel moderated by Andre Picard.

Dr. Yong (far right beside Steve) participating in a public panel moderated by Andre Picard.

Dr. Yong has been an important leader in developing the MS research community in Canada and internationally. He has also made very important contributions to the field through his research. His interest in re-purposing approved drugs as novel (and affordable) MS treatments stands out in particular. I remember some of the early experiments from his group testing minocycline as a therapy in animal models of MS from my time as a graduate student at the University of Calgary, and it is very exciting to see these come to fruition in human trials many years later.

 
 Steve, Ravi, and Sara providing a London MS Update

Steve, Ravi, and Sara providing a London MS Update

 

The scientific symposium for the day turned out really well. Our external panel members gave outstanding presentations, introducing attendees to the excellent and collaborative research that is occurring in Canada and internationally. I had the opportunity to talk about our work and collaborations with Drs. Ravi Menon and Sarah Morrow here at Western University.

 Kate....

Kate....

 and Yodit presenting their work. It was pretty dark, hence the blurry pics. 

and Yodit presenting their work. It was pretty dark, hence the blurry pics. 

The day ended with the Leaders in Innovation Dinner honoring Dr. Yong as well as guests Ann and Mitt Romney. Kate and Yodit had the chance to talk about their work with attendees at the reception.

 
 end of a long, but good day. Yodit, Steve, and Kate at the Leaders in Innovation Dinner.

end of a long, but good day. Yodit, Steve, and Kate at the Leaders in Innovation Dinner.

 

Are you in London ON and interested in hearing about world-class research?

You are welcome to attend the J. Allyn Taylor International Prize in Medicine Symposium in Multiple Sclerosis.

Join us as we celebrate research innovations in multiple sclerosis (MS). The day includes presentations by experts in the fields of diagnosis, treatment and prevention of MS, a panel discussion moderated by André Picard, health columnist with The Globe and Mail, and a keynote lecture by the 2017 J. Allyn Taylor International Prize in Medicine recipient, V. Wee Yong, PhD.

Learn more about all our speakers and see our full day agenda: http://www.robarts.ca/symposium.

Event Details:

  • Wednesday, November 15, 2017
  • 9:00 a.m. - 4:00 p.m.
  • Auditorium A, University Hospital, London Health Sciences Centre

RSVP:

New this year the full day Symposium is open for everyone to attend but space is limited and you must RSVP

Hope to see you there!

For those interested, you are also welcome to buy a ticket to join us at the associated Leaders in Innovation Dinner. More information on that here.

Meet this year's team

 left to right-ish (you'll figure it out): Heather (tech), Yomna (undergrad), Kate (post-doc), Yodit (PhD candidate), Maitri (undergrad), Rajiv (PhD candidate), and Steve (lab head). 

left to right-ish (you'll figure it out): Heather (tech), Yomna (undergrad), Kate (post-doc), Yodit (PhD candidate), Maitri (undergrad), Rajiv (PhD candidate), and Steve (lab head). 

This year, we're pleased to welcome two Honors Thesis students to the lab! Yomna El-Sakka (top left) will be working with Yodit and Rajiv to characterize spinal cord pathology on some disease models that we're working on. Maitri Makwana (front, centre) will be working with Kate to finalize the development of a reagent we're developing for use in a collaboration with the London MS clinic. 

 

KerfootLab and Friends at the 2017 PwC MS Bike Ride

 Team Microbiology & Immunology: (left to right) KerfootLab members Heather, Rajiv, Kate and Yodit. Dikeakos Lab members Aaron and Brennan. And then Steve. 

Team Microbiology & Immunology: (left to right) KerfootLab members Heather, Rajiv, Kate and Yodit. Dikeakos Lab members Aaron and Brennan. And then Steve. 

As we have for the last few years, members of the lab and others from the Department of Microbiology & Immunology took part in the 2017 PwC MS Bike Ride from Grand Bend to London and back.

 Heather and Kate make wraps

Heather and Kate make wraps

 Rajiv checks out the wraps

Rajiv checks out the wraps

Heather, Kate, and Rajiv donated their considerable talents to help feed hungry riders at the half-way point on the first day.

 Start line, Day 1

Start line, Day 1

 Start line, Day 2. Still smiling!

Start line, Day 2. Still smiling!

Yodit and Steve were joined by Brennan and Aaron from the Dikeakos Lab to make the ride from Grand Bend to London on Day 1 and then back again on Day 2. Everyone made it safe and well fed, thanks to the great organizers and volunteers that made it a great day. 

 
 150km later: tired, hungry, but still smiling.

150km later: tired, hungry, but still smiling.

 

Other $1.4m was raised by this ride to support both research and community programs that are run by the MS Society of Canada. This is a great opportunity to that the MS Society for their support; Rajiv is funded by an MSSOC PhD Studentship and Kate holds an MSSOC Post-Doctoral Fellowship. Thanks must also go to all of the volunteers and donors that make it possible for the MS Society to do the important work that it does. 

New KerfootLab Publication

Our most recent paper just came out this week in the Journal of Immunology. It has been available online since early June, but appears in print and gets an official (and increasingly irrelevant) volume and page number today.

 
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In this paper, we use our unique tools to track autoimmune, and myelin T and B cells in a model of induced anti-myelin autoimmunity in mice. In human Multiple Sclerosis it has become apparent that B cells are very important players in promoting disease progression; in fact B cell targeting therapies have been approved for treatment of MS, including for the first time the progressive form of disease. However, we don’t know much about how these cells drive disease, and much of our research aims to figure this out.

B cells are known to invade the brains and spinal cords of people with MS, and they often form clusters with T cells adjacent to demyelinating lesions. Our initial assumption, based on what is known about the T cells that infiltrate the CNS in autoimmunity, was that many or even most of these B cells would be the ones that themselves target CNS autoantigen. We were surprised to find the opposite and that, if anything, activated autoimmune B cells are excluded from the inflamed CNS.

The usual caveat that this is a study in an animal disease model and not in human MS should be noted when interpreting findings from this paper. However, similar models of disease have previously revealed fundamental properties of the CNS/immune system relationship, and there is no reason to think that this is not the case here. Further, while some findings from human MS tissues have been interpreted to suggest B cells in the CNS are activated and target autoantigens, after closer reading of studies we are not convinced that this is the case. As with any study such as this, time will tell which is correct, but we will continue to address this issue in future studies.

Funding: This work in this paper was funded from an operating grant from the Canadian Institutes of Health Research (CIHR). Yodit’s stipend is funded from an Ontario Graduate Scholarship and Rajiv’s stipend is funded from a studentship from the MS Society of Canada. Please check out our funding page for more information.

A note about access: The conditions of our funding stipulate that publications must be freely accessible within a year of publication, and in accordance with this it will be possible to access the full and final version of this paper through the journal website within a year. Allowing early open access would have cost our research budget thousands of dollars over the ~$3000 CAD it already cost to publish this paper (lots of colour charges for pretty figures). If you want to read our paper but can’t get access, please contact us and we will do our best to get it to you.

Kate takes a well-earned break from the lab and has a chance to talk about her work back home

After a challenging and rewarding 14 months of my new life in Canada, in April this year I headed back to Adelaide, Australia to visit my family and friends, and importantly seek out some sunshine and the ocean.

 A beautiful autumn day down at the beach (Brighton, SA, Aus)

A beautiful autumn day down at the beach (Brighton, SA, Aus)

There were lots of lunches down the beach and dinners in the city so I could spend quality time with the people I have missed and see how Adelaide had changed in my absence. I also took the opportunity to catch up with my PhD supervisor and my previous lab members, and I was asked to be interviewed for a magazine put out by the student association at UniSA, to talk about my transition to Canada and my life as a scientist.

With a keen interest in science and an undergraduate degree from UniSA, Kate is now pursuing a post-doctoral degree in Canada. She speaks to us about her journey from Adelaide to Ontario and her work as a scientist.
— In[ter]view: Kate Parham

One of the highlights of my trip was going to see my favourite sports team Port Adelaide Power play Australian rules football, something I really miss while here but thanks to the internet I don’t have to miss out completely!

 Australian rules football. Port Adelaide vs. Carlton (we won!!) @ Adelaide Oval, SA, Aus.

Australian rules football. Port Adelaide vs. Carlton (we won!!) @ Adelaide Oval, SA, Aus.