New publication from us

note: this post is part of our ongoing experiment with SciCom and social media.

We’re excited to tell you about our new study, published today in Cell Reports.

We, like other Immunology labs, spend much of our time trying to understand how the immune system decides what it’s going to attack and how. T cells and B cells are two families of immune cells that are both responsible for identifying a specific target (called an “antigen”) and directing the immune system to attack it, although they go about that role in very different ways. Still, under most circumstances, B cells and T cells that recognize the same antigen collaborate with each other to determine how the immune response will develop, and this impacts the effectiveness of the resulting response. Figuring out how this is achieved is a very active field in immunology.

Lead author and recent PhD grad. Dr. Rajiv Jain.

Our study, led by recent PhD grad Dr. Rajiv Jain, started with a very simple question:

Does the immune response to a self-antigen, in this case to myelin oligodendrocyte glycoprotein (MOG), a protein found in the central nervous system (CNS – brain and spinal cord), develop differently compared to a response to a more “normal” foreign antigen?

We had several reasons for wanting to know the answer to this question. One is that we and others use MOG protein to induce CNS autoimmunity in animals to model human diseases such as Multiple Sclerosis (MS) (see more about that here, and about our MOGtag proteins here). We have been using these models to try to understand how B cells contribute to disease, and so far have focused mostly on the B cells that infiltrate the inflamed CNS (see here and here). However, after a few surprises (to us, at least) it became apparent that we needed a more in-depth understanding of the basics of the B cell response to MOG antigen.

A second motivation for this study is that, in addition to our more MS and related disease-oriented studies, we are also very interested in simply understanding how the immune system works and how it tailors its response to a specific target. So far, nearly all investigations of this process (including our own primary and collaborative studies – see here, here, and here) have studied the response to a very short list of model target antigens. We had a hunch that the response to MOG might be different enough to be a useful tool to dissect the signals responsible for determining immune outcome, allowing us to address these types of questions from a different perspective than we or others have used previously.

It turned out that our hunch was correct. When Rajiv immunized mice with MOG protein, the B cell response was initiated relatively normally compared to the standard model foreign antigen, but it wasn’t sustained. Instead, the organized B cell response collapsed early into what at first looked like Memory B cells, specialized cells that respond the next time you see the same antigen. However, it turned out that these cells didn’t live very long, so the memory response to MOG failed. We performed some experiments to determine which features of the B cell response to MOG were controlled by the T cell partner, and also manipulated the antigens in different ways to alter the outcome of the response.

So, why is any of this important? To other Immunologists, this study represents another step forward in our cumulative understanding of how the immune system controls the outcome of its response to a target antigen. This is inherently important to those of us who want to understand how biology works. It’s harder to explain the value of fundamental research like this to those outside of the science community. If this were a standard press release, this is the part where we’d say something like “in 20 years, these findings could result in better treatments for autoimmune disease, or better vaccines”. This could, in fact, turn out to be the case; fundamental studies like ours asking similar questions about how immune cells signal to each other led to the development of Checkpoint Inhibitors – and this work was just awarded the 2018 Nobel Prize in Physiology or Medicine for the way they have revolutionized the treatment of many cancers. In fact, if you dig into the history of nearly every major advance in medicine or technology you will find similar foundations on so-called curiosity-based research.

Science is a group effort! Rajiv (top row, second from the left) led the project, and Yodit (top row, second from left), Heather (Bottom row, left), and Kate (second from left) all contributed to this publication. Past undergrad Emiliano Romanchick (not in this picture) also contributed to the study and is an author on the paper.

Want to be a part of the team? We’ll be looking for a new PhD and undergraduate trainees soon!

Nevertheless, there are more short-term outcomes from our new study for our own work. First, we’re applying what we’ve learned about the anti-MOG B cell response to our investigations of B cells in autoimmune disease. The findings from this study will help PhD student Yodit Tesfagiorgis to refine the questions she’s asking in our more disease-oriented work. Also, we now have a unique model to study the signals T cells use to affect what B cells do in an immune response. Post-doc Dr. Kate Parham is pushing these investigations forward and she already has some tantalizing results that we’re looking forward to sharing with you one day in a future publication.

 A Note About Funding:

The work we do is entirely dependent on your support, whether it be through your taxes or donations to funding agencies. Thank you! Lead author Rajiv Jain was funded by a studentship from the MS Society of Canada. They also fund co-authors Yodit Tesfagiorgis (PhD Studentship) and Kate Parham (Post Doctoral Fellowship).

Operating funding for the lab (covering the actually cost of experiments, not just people) has come from a grant from the Canadian Institutes of Health Research.

Taking a trip to St. Francis Xavier University for the endMS Sprint Face-to-Face meeting

Sorry for the delay with an update on my trip to St. Francis Xavier University, but here it is! Being a part of the endMS SPRINT program has allowed me the opportunity to travel to Antigonish, Nova Scotia.

Meeting up with my Sprint team allowed us the opportunity to determine exactly what we wanted our review paper to be about. We also had the opportunity to explore Antigonish while tackling the reference screening of 8016 papers without the constant reminder of lab work!

Days consisted of morning walks to the coffee shop from our cozy AirBnB, followed by a full day spent in the Schwartz School McKenna Center sorting through the references we acquired. Antigonish was a wonderful, quaint town and Dr. Lindsay Berrigan was a wonderful host!

p.s. Pacha Mama was an amazing place to eat, which sits right next to the Waffle Bus Stop (another delicious place to eat).

Maitri checks in

(Editor’s Note: We recently got this note from Maitri Makwana, one of our undergraduate honour students from last year, in the mail (real mail!). We are always excited to hear what our lab alumni are up to after they move on, and how they’re using what they learned in the lab in the next steps of their career. Maitri gave us permission to share her update here on the lab blog. Enjoy!)

Hey Kerfoot Lab! How are you guys?! I haven’t had the chance to visit London since I left, is I’m sending this souvenir -a new addition to the freezer collection- as a memory from my trip to the Blue City this summer.

#GirlPower 🌸💪🏾 (Maitri 3rd from the right)

(Ed. note: Kate started a lab tradition where we add a magnet to the freezer door to commemorate any trips)

Project Women Empowerment was a real eye-opener and an incredibly gratifying experience; I wish I could tell you in person just how impactful it was. From teaching Science and English to girls raised in poor communities of Jodhpur, I learned a great deal about their culture, values, struggles and just how humbled I am for the privileges and endless opportunities I have here in Canada. Apart from surviving 45-degree weather and adjusting to the not-so-luxurious lifestyle, I met some inspiring individuals along the way, travelled a fair bit, ate lots of spicy street food and learned how to speak (broken) Hindi.

Team Women Empowerment (Maitri is in the front row, 5th from the right)

Since I got back, I’ve been finishing off some med school applications while doing a research internship at ApoPharma Inc. We’re currently doing metabolism and toxicity studies for drug candidates that could be used to treat iron dysregulation in Parkinson’s Disease. My supervisor’s a hardcore chemist which means I’ll be learning some fancy HPLC/LCMS techniques. Pharma research definitely has a different feel compared to academia, but it’s been great so far -everyone’s helpful, the work is stimulating, and I get to use some of the skills I’ve learned from you guys at the Kerfoot Lab.

Hope to hear back from you soon!

-Maitri

We made a PhD! But what's a PhD good for?

Research labs don’t just generate new science; we also produce new scientists! Our most lasting and important impact will be through the trainees who pass through the lab.

Rajiv in his armoured suit presenting 5yrs worth of work in 40 min.

We’re very excited that Rajiv has successfully defended his PhD thesis and is now Dr. Jain! During his time here, Rajiv developed several new techniques and reagents that will continue to be important to our lab’s research for years to come. His primary project, which focused on understanding how T cells control B cell responses to different antigen targets, and how properties of those antigens themselves influence immune outcome, has just been accepted for publication and we’ll talk more about it soon.

The cake was not a lie.

The rest of the team claims some of the credit (and cake).

Rajiv is now planning his next steps to continue his training as a Post-Doctoral Fellow. He’ll tell you more about that himself in an upcoming post. Post-Doctoral training is an opportunity to learn new techniques, branch out into a new field of research, and gain more experience and independence. It’s often a necessary step for the next stage in a science career, whether that be in academics, industry, or something else. In fact, most PhDs go on to use their science training outside of academia.  

Signed proof Dr. Jain has completed his thesis to the satisfaction of his supervisor and exam committee.

It’s becoming all too real: Rajiv’s empty desk and pile of lab books. We’ll miss you Rajiv!

PhD’s are sometimes accused of been over-specialized, and not useful outside of their niche specialty. Nothing could be further from the truth. During their PhD program (and Rajiv is an excellent example), students train to and become adept at thinking creatively to ask new questions and solve new problems; develop new approaches to overcome unforeseen hurdles; troubleshoot issues as they arise; become technically expert in hands-on procedures; to develop and adapt procedures to new uses and environments; to quickly become expert in a new topic that unexpectedly becomes important to their project; to clearly communicate highly complex and technical topics through different media, including written papers, oral presentations, and visual figures; to train and mentor more junior students; and to collaborate with other experts to solve important problems. What industry would not value such highly flexible and broad expertise?

Up for a challenge? We’ll be looking for our next PhD trainee soon. It could be you!

Over the next few months we expect to start the search for our next PhD student. If you’re considering your own next steps and willing to take on a challenge (and it is a challenge), PhD training can be a great entry point into many careers.

Yodit at the 2018 endMS Summer School

This year, I had the opportunity to attend the annual endMS Summer School, run by the Multiple Sclerosis Society of Canada. The theme of the weeklong retreat was “Environmental and Lifestyle Factors associated with MS”. Hosted in downtown Toronto at the Hospital for Sick Children’s Peter Gilgan Centre for Research and Learning, I joined a diverse group of researchers ranging from physicists, engineers, physical therapists, psychologists, MD-PhD’s and, lastly, immunologists like me!

(Photo Credit from endMS website) The incoming and outgoing SPRINTers, 2018! Yodit second from bottom left.

The topics covered included: Trials on progressive MS; Modeling MS in Mice Models; the Microbiome; Diet; Vitamin D; Neuropsychiatry; Effects of Smoking; Physical Activity Interventions in MS; as well as ways to halt Pediatric MS and trigger the initiation of new oligodendrocytes for the treatment of MS. Furthermore, we were given amazing networking advice and interview prep skills for all our future endeavors.

Group 2 (we're not flashing the peace sign) visits the Art Gallery of Ontario during a short break in the action.

I’ll also be participating in the endMS SPRINT program over the next year, through which I have the fortunate opportunity to work with a team of SPRINTers under the guidance of Dr. Lindsay Berrigan from St. Francis Xavier University. We’ll return to next year’s endMS Summer School to present the results from our SPRINT Team Project looking at cognitive dysfunction in MS.

Congratulations to our Honors Students!

Yomna, Steve, and Maitri in their wizarding robes for convocation.

Congratulations to Yomna El-Sakka and Maitri Makwana for graduating from the Microbiology & Immunology Honors Program! It has been a pleasure having you both in the KerfootLab during your honors year. We wish you all the very best for all your future endeavours!

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 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

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....

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.

We're in Rapport Magazine!

Steve and his "serious face"

Check out this great article describing how we work with other Schulich and Robarts clinicians and scientists to learn more about Multiple Sclerosis and how to help those living with it.