📷 UofT Department of Immunology
Journalist: Haleema Ahmed
Haleema: Hello everyone and welcome back to SciSection. I’m Haleema, your journalist for this week, and today we are delighted to have Dr. Jennifer Gommerman. Dr. Jennifer is a Professor & the Associate Chair of Graduate Studies in the Department of Immunology at the University of Toronto. Additionally, she holds the Canada Research Chair in Tissue-Specific Immunity. Welcome, Dr. Jennifer!
Jennifer: It’s great to be here, thank you.
Haleema: So to begin, could you provide a description of what your academic career looked like that led you to where you are today?
Jennifer: Sure, so in broad strokes, I trained as an immunologist. I did my undergraduate and graduate degrees at the University of Toronto which is one of the strongest immunology departments. From there, I decided to pursue further post-doctoral training at Harvard Medical School where I broadened my expertise to include animal models of disease and infection. I went to Industry for about three years where I worked at a company called Biogen in Cambridge, Massachusetts; I learned a lot about how to develop drugs and therapeutics and I also gained an interest in the human disease multiple sclerosis. In 2003, I returned to Canada and started my lab at the University of Toronto. As an assistant professor, my initial research was to continue the work I had started with multiple sclerosis and also study molecules of a family called the T and F family. Then through the years, as my lab grew and my research broadened, I became very interested in the mucosal immune system in the gut and how it impacts diseases that are far from the gut such as multiple sclerosis. MS is an autoimmune disease of the brain and central nervous system and spinal cord. Then coming up to the present day when COVID hit, we as a lab realized we had a fair bit of expertise in studying mucosal immune responses. We had done a lot of work on a virus called Rotavirus and we knew how to measure the antibodies that are made to Rotavirus. We realized that because Sars-Cov-2 is a virus that enters through mucosal surfaces in the nose and the mouth, that was something we needed to understand and learn more about. We partnered with another lab at Mount Sinai in Toronto and we developed a test to measure antibodies in the blood and our case, saliva as a biofluid that will be a proxy of what might be going on in the local, mucosal immune response in the oral cavity. We just posted a preprint of that at work, if you are interested, at the med archive and it is under peer review. Hopefully, that will be published soon. That is where we are right now.
Haleema: That is very interesting and I wanted to ask, were you always fascinated with science and biology from a young age and teenagehood? Did that inspire your work today?
Jennifer: Well, I wasn't specifically interested in science but it was something that I did well in high school; I got good grades in in my math and science courses and when I started university, it seemed natural to continue with some science because it was something I liked but honestly, I took a lot of different courses throughout my university career and toyed with other subject matters such as sociology and literature and even French. I didn't settle on a major until my third year. I mean we have to declare a major in our 2nd year at UofT and I declared it to be microbiology but in my third year, I took this immunology course and it was like a thunderclap. I realized it was something I wanted to take more seriously because it was just a system I had never even thought of or considered; we have this defense system that permeates every tissue of our body. So I switched my program of study over to immunology and it happened that microbiology was a nice pairing for Immunology so I actually had a blended major specialist in those two subjects and then I carried on from there. It wasn't so much that I was laser-focused from high school onwards. I just sort of went where my interest took me.
Haleema: Is that something that you would recommend to undergraduate students? Kind of dipping their feet into various subject matters instead of being a little more close-minded?
Jennifer: Yes, in fact, my oldest son is just starting the first-year university next year. His passion is math and physics but he also loves thinking about politics and social justice and social change and so we talked a lot about what an elective looks like for him because electives can morph into something. I think it's really hard to know when you’re 18 what you want to do for the rest of your life so it's good to keep an open mind and also different courses give you different skill-sets. You're going to need breath requirements, of course, but if you only gravitate towards those courses where you only need to do multiple-choice tests and so on, you are never obliged to write something down. You don't work that skill as much as you could and it’s like a muscle. If you want to be a good writer, for example, you need to write and so I think that the advantage of taking a broad array of subjects is that you become a more well-rounded student not just in terms of what you know but what you can do and how you can apply that to your future career. As a scientist, I would say I spend most of my time writing, and to be a good scientist and to do well, publishing papers and get a grant, you have to write. I had a bit of a leg up because I had taken courses where I had to write critically early on.
Haleema: That is amazing advice. I think you mentioned before that a large portion of the lab you lead at UofT involves studying Multiple Sclerosis. For those who may be unaware, what exactly is MS and why is it such a fundamental piece of your work?
Jennifer: Multiple Sclerosis is an autoimmune disease. An autoimmune disease is a disease where your immune system starts attacking your tissues. Examples are multiple sclerosis where the immune system attacks the brain and spinal cord or rheumatoid arthritis where the immune system attacks the joints or psoriasis where the immune system attacks the skin. So Multiple sclerosis is really important to study among Canadians because we have the highest rate of multiple sclerosis in the world. Some people think it's because of our latitude or maybe some of the environmental influences or maybe genetics. We have a high rate of this disease. MS is interesting because there's been a lot of therapies that are pretty good at managing the so-called “relapsing-remitting version of MS” and it's a cool thing to study from an immunological point of view because we’ve seen progress; we have seen a deeper understanding in terms of the impacts on CNS but they're still forms of MS that are very untreatable like the progressive form. So there is still a lot of unmet clinical need so I study it for two reasons. One; people are suffering from this disease in Canada and it's a cruel disease and I'd like to see better therapies in both the relapsing stage but something that will impact the progressive stage as well. Secondly, as a sort of immunological disease, it's kind of got everything. You can study how immune cells are first triggered to respond to proteins in particular myelin in the CNS and so that's a whole field of study. You can study how the immune cells go from the lymph nodes up to the CNS and how they cross the blood-brain barrier. You can understand how immune cells interact with glial cells in the brain and what that looks like; that is something incredibly difficult to study but it is making a lot of progress in the age of RNA sequencing and multi-parameter analysis. You can study what aspects of the human body are used in the immune system to quiet inflammation and to encourage repair. There are so many different points for an immunologist to get in there and try to understand this disease. It makes it a very interesting and exciting topic for an immunologist to tackle.
Haleema: It appears to be a very diverse field and in your research, have you ever had a specific finding or a study that you have found particularly interesting; maybe even groundbreaking for treating the disease?
Jennifer: I would say that in my career as a principal investigator and as a professor, I have had 2 findings that knocked my socks off and I was pleased about. We published a paper in 2011 where we showed that this isn't about MS; it's about a kidney disease called IGA nephropathy. We were able to show we could model this disease in a mouse model and nothing's known about this disease in terms of how to best treat it. It's treated with steroids and it's also the most common form of what we call glomerulonephritis and some people who have this disease often need a kidney transplant eventually. It's not a good disease and what we noticed are two things in this animal model. First of all, there was this cytokine called Baff that was elevated and it was really important for mediating the disease. Secondly, the disease did not manifest itself if the mice didn't have the microbiota. Actually, at McMaster, we were assisted in making these mice germ free. In other words, they don't have a microbiome so they don't have any of that natural bacteria that we would ordinarily have in our gut or on our skin. So these mice were completely sterile and when that was the case, they didn't develop kidney disease. In retrospect, we know so much more about the microbiome now that maybe that's not a surprise but at the time, that was a big surprise and that paper got pretty much ignored the field for a few years, at least in the IGA nephropathy field, where they didn't buy it. They just, for whatever reason, though wasn't cited, so it was kind of ignored. But then some studies started coming out that confirmed our findings. For one thing, in humans, when you assess the genetics of these patients, one of the top hits was a cytokine that's related to Baff called April and we had found that the patients with IGA nephropathy did have elevated levels of April. So this unbiased genetic screen picked up the same pathway that we have identified which was very gratifying. In addition, there was a growing appreciation that this disease might be treatable by using steroids that act only in the gut which prevents inflammation in the gut. I wasn't central to that field as I was sort of dabbling on the edges, but then out of the blue I got an invitation to participate in the IGA nephropathy Congress they have once every two years and they gave me a keynote slot to speak and so suddenly the paper was being paid attention to. That was cool as a scientist to watch our research go from basic findings to the clinic and to see some work that was coming out that people were also starting to design drugs around this concept that the microbiome and the cytokine Baff or April might collaborate to cause problems in the kidney. It wasn’t the only study that got them there but it was an important one so that was kind of cool.
Haleema: That is incredibly interesting and now segwaying into some of the other work that you are doing, I recently read a UofT article featuring your take in COVID-19 vaccine development which is something I think you mentioned in our conversation earlier. I wanted to ask what type of work are you conducting in your lab related to that pressing need.
Jennifer: We hypothesized early on that there must be a local immune response in the oral cavity because that's really where the virus enters. We know that it proliferates in the upper airways while you're asymptomatic. Then the virus transitions to go in deeper in the lungs and cause a lot of problems there. We also know that a lot of people don't get any symptoms so we think that initial immune response is probably really important. We went about measuring antibody levels in the saliva while my colleague worked at Mount Sinai and was measuring them in the blood, being completely independent work. Then we put our data together and found that they correlated well. It was gratifying that saliva might be a biofluid to think about when we’re looking for antibodies although it is not quite as sensitive as blood. But the second thing that we learned from those experiments is that we had samples from a whole variety of time points from the acute phase of the disease to convalescence when people have recovered from the virus and were 3 and 4 months out from their original symptoms. What we found is that the antibody levels for some of the tests that we did, not all but some, were quite stable through those 4 months. Other studies have come out at the same time, and really in the last 2 weeks, that confirmed that finding that even in asymptomatic people, many of them make a very stable antibody response that can last for a few months as far as we've looked because the pandemic hasn’t been with us for very long. So that was really good news because there was a previous study, that came out a couple of months ago, that said our antibodies crash after we get this virus and our neutralizing antibodies, the antibodies get rid of the virus, were also declining. So far that study has not been replicated in these other studies and there could be lots of reasons for that. But it means that our initial doom and gloom thinking that "oh my gosh you can't make a good immune response to this thing", is probably incorrect in that most people, not everybody, but most people make a good, durable antibody response to this virus and that bodes well for vaccine design. We can make an antibody response to this virus that lasts at least for 4 months, then a vaccine is probably going to work. Whether it works for a year, 2 years, 6 months we don't know, but at least it rationalizes all of these ongoing vaccine efforts and it gives me a lot of hope that we're going to get something that's going to give reasonable cellular defense against Sars-Cov-2. If it's designed properly, then that should also confer some herd immunity against the virus if everyone takes it or as many people who can take it, take it.
Haleema: That is amazing and I hope that some of that work can transfer for some vaccine development that I think a lot of us are looking forward to. I guess with everything that we've discussed immunology appears to definitely be a very very interesting field and so what can an undergrad student interested in Immunology expect in their academic career or their career choices?
Jennifer: Well first of all if you’re interested in immunology, most universities offer immunology courses at the undergraduate level - I know McMaster has a few courses on immunology. So the best thing to do is to take a course and see if your interest persists after that course. As a field, it can be a little bit daunting because it is very jargon-heavy, and unlike genetics where we can say you know this promoter regulates this gene, with Immunology, there's a lot of subtle nuances and not everyone likes that and some people shy away from studying immunology because of that and I don’t blame them (laughs). I struggle with that too so I think just take a course and see whether this is something you want to do. Don't rely on your exposure to the field by whatever is in the popular literature and so on - you should just take a course. If you do like it, then I would recommend thinking about what intrigues you most about immunology and approach some professors and see if they would take you as a student under their lab during your undergraduate period. At UofT, this typically occurs in the summer of the third year that grows into a project, an honors project, that would occur throughout your fourth year. That is a good opportunity to get some hands-on experience to see whether this is a field you want to pursue as a career. Those are the two main things I would do - take a course and if you’re still interested, do some lab work if that is available to you at your university.
Haleema: You mentioned the emphasis on lab work and I think naturally you receive a lot of emails requesting to volunteer in your lab. What is your advice or what do you look for in prospective students in your lab and how do you think students can better contact professors through cold emailing or whatever method they choose?
Jennifer: It's really hard because we do get a lot of cold emailing and my lab is full right now. It's a pity because I get a lot of great people applying to the lab and COVID has further complicated things as we’re only operating at 50% capacity. I have to give precedence to current lab members especially graduate students and postdocs who have ongoing projects. I can't take up some room in my lab for someone brand new when those people are already got a foot in the door so it's tough. You may want to think about approaching some of the newest PIs because they're not as well known so they are not being bombarded with cold emails as much as someone more established. Students often just apply to the professors that they know of but PIs that are just starting their labs are great and can give you a great training experience because they’re gonna have more time for you. Their lab is big and they’re keen to practice their mentorship skills. I would consider some of the more junior PIs to contact. When you are contacting PIs, whether they be junior or senior, a form letter is not going to work, you might not even get an answer just a form letter, but if you've identified a particular reason why you are interested in their lab and your articulate that in your letter, that will help you. But don't get discouraged if you don't get replies because communicating this from the other end. If I get three or four of these per day, I'm not going to necessarily have enough time to answer all of them on top of all the other email load that we have from our work and daily lives so don't be discouraged. Don't take it personally if you have to contact tons and tons of people because that's part of the process. Most universities have programs where you take it as a course to do lab work and in those cases, there is more security in landing a lab position because it's a part of the course. So like I said, there's an honors course at UofT in a program that places students in labs, although the student has to identify the lab, and we give precedence to students that are in the specialist program as opposed to the major program because we have fewer students in the specialist program and they’re taking more immunology courses than the majors. If you’re interested in a topic, then I would recommend thinking about doing specialist programs that will not give you as much latitude, unfortunately in your electives, but it will give you a little more priority in terms of getting a lab position.
Haleema: That is incredible advice and I think a lot of our listeners tuning in can benefit from it. On that note Dr. Jennifer, we would like to thank you so much for joining us here today and telling us all about your amazing work.
Jennifer: Thanks Haleema and good luck to you and all your colleagues.