Dr. Manu Rangachari


photo of Dr. Manu Rangachari

Dr. Rangachari trained as a molecular and cellular immunologist during his Ph.D. studies under the supervision of Dr. Josef Penninger in Toronto and Vienna  and postdoctoral training under Dr. Vijay Kuchroo at Harvard Medical School. With a long-standing interest in T cell-driven autoimmune mechanisms, during his postdoc, he focused his attention on these mechanisms in the context of multiple sclerosis (MS). In particular, he studied the role of "immune checkpoint" molecules in reducing T cell inflammation in mouse models of MS. In recognition of his contributions to MS research, he received the prestigious "EMD Serono Canada and endMS Network Transitional Career Development Award". Currently Professor of Medicine at Université Laval, he has developed a research program focused on the role of the adaptive immune system in the secondary progressive phase of MS (SPMS). He is motivated by the fact that approximately 40% of MS patients develop a SPMS, yet treatment options are limited. Also, despite substantial clinical evidence that lymphocytes, a type of white blood cell (i.e., T cells), are implicated in SPMS, the number of available animal models to study it are limited. As a FRQS senior scholar, Dr. Rangachari has generated one of the few animal models that can allow researchers to study the role of T cells in SPMS. Intriguingly, the frequency of mice that transition to secondary progressive phases is very similar to that seen in humans. Thus, there is now the ability to dissect and study the molecular and cellular mechanisms that drive SPMS. Dr. Rangachari has a specific interest in the role(s) played by biological sex in T-cell driven autoimmunity in the central nervous system and more recently, has explored T cell: B cell interactions in progressive MS-like disease.

Learn more about Dr. Rangachari

What is the focus of your research? How did you become interested in MS research?

Some might argue that my interest in MS research began way back in the 1980s when I participated several times in the MS Canada's Readathon program! I believe my parents still have the stuffed animal that I received for my efforts. As an "adult", I became interested in MS research as I was completing my PhD studies in 2006. I had trained as a cellular immunologist with a specific interest in autoimmune diseases. As MS is an autoimmune disease with a very high rate of incidence in Canada, it was logical for me to want to better understand the ways in which it is regulated by the immune system.

What inspires you to continue advancing research in this field?

Enormous strides have been made in treating relapsing-remitting MS but the outlook for people with progressive MS is less optimistic at the moment. About 1 in 600 to 800 people in Canada live with progressive MS – about the population of Charlottetown, PEI or Brandon, Manitoba. This is a substantial number of people who face decades of increasing disability. By increasing our understanding of what causes or aggravates progressive MS, I hope to shed light on new drug targets and treatment strategies for the future.

How do you hope to change the lives of people living with MS through your research?

My currently funded MS Canada research focuses on what is known as “gene imprinting”. According to
this concept, a person inherits two copies of a given gene from each of their parents. The DNA sequence of both copies is normal – there are no mutations. However, one copy comes with extra “annotations” that prevent it from functioning properly. The events that cause genes to be annotated in this manner are currently unclear, but we have evidence in mice that gene imprinting can impact their ability to develop severe progressive MS-like disease.

We are doing basic research that is likely quite a while from making an impact in the clinic, but by
identifying genes that are imprinted in this manner, we could then see if this also happens in people with MS. This could, in future years, lead to new treatments or develop tools to predict outcomes in progressive MS.

What do you enjoy most about your research? What are some of the challenges you face?

Discovering something new that literally no-one else in the world knows is an exhilarating feeling, especially when it has the possibility of one day helping people with diseases such as MS. I also enjoy interacting with people from many different countries and backgrounds. Research can definitely be frustrating at times - experiments don't always give clear results, which takes you back to the drawing board. However, I like to think that my 4 decades as a diehard fan of the Toronto Maple Leafs has taught me a thing or two about perseverance!

How important is the support from MS Canada in your research?

The support of MS Canada is essential both for my research and more generally for MS research in Canada. Thanks to MS Canada, we have continued to be leaders in the study of this disease. As someone who has been funded almost continuously by MS Canada since 2007 - first as a postdoctoral fellow, then as an independent researcher - their support has been essential to the success of my program. A pretty good return on the money I raised through the Readathon way back when!