Postdoc Feature Series with Silvia Pires

Postdoctoral Associate with Randy Longman Department of Medicine

Recent Achievements:

• Award for best data blitz presentation, Weill Cornell Medicine Postdoc Research Day 2020
  • American Association of Immunologist Careers in Immunology Fellowship - Effect of type III interferon on innate immunity to Staphylococcus aureus.

Recent Publications:

• Pires, S, Peignier, A, Seto, J, Smyth DS, Parker D. “Biological sex influences susceptibility to Acinetobacter baumannii pneumonia in mice” JCI insight (2020). doi: 10.1172/jci.insight.132223.
• Pires, S. D., Oliveira, R., Moradas-Ferreira, P., & V Mendes, M. (2020). The Onset of Tacrolimus Biosynthesis in Streptomyces tsukubaensis Is Dependent on the Intracellular Redox Status. Antibiotics, 9(10), 703.
  • Wong Fok Lung, Monk IR, Acker KP, Mu A, Wang N, Riquelme SA, Pires S, Noguera LP, Dach F, Gabryszewski SJ, Howden BP, Prince A. “Staphylococcus aureus small colony variants impair host immunity by activating host cell glycolysis and inducing necroptosis.” Nat Microbiol. (2020).
  • Pires, S., & Parker, D. (2018). IL‐1β activation in response to Staphylococcus aureus lung infection requires inflammasome‐dependent and independent mechanisms. European journal of immunology, 48(10), 1707-1716.
  • Pires, S, Jacquet, R and Parker, D. Inducible Costimulator contributes to methicillin- resistant Staphylococcus aureus pneumonia. J of Infectious Disease. doi: 10.1093/infdis/jix664, (2018). PMID: 29378030.

What was your path to your current postdoc position?

I'm originally from Portugal and I did my PhD at the University of Porto. My graduate work was in a completely different field from where I am now, microbiology, and I was working with soil bacteria. Streptomyces are soil bacteria that have these very impressive secondary metabolites, which encompass about ~70% of the bioactive compounds that we use. The one I was working with produced an immunosuppressor and I remember being fascinated that a soil bacteria was providing an immunosuppressor that could be used in human patients. It was during this same time that I realized as interested as I was in bacterial metabolism, I was becoming more and more interested in host-pathogen interactions and thought it would be cool to learn about the host side of that interaction. I had always

dreamed of being in New York, even as a child, so I applied and got a postdoc position at Columbia University to work on host-pathogen interactions. It was a little bit overwhelming because I was moving to an area of research so different from my PhD and I was unfamiliar with the background. But at the same time, it was a good experience to learn so much in a new area.

After three years at my first post-doc, I wanted to move beyond inflammation in the lung (my topic of study at the time). I had become intrigued by microbiome research, and the gut is the biggest area of microbiota, so I began to think a lot about inflammation in the gut. This led me to Cornell, where I now work as a postdoc at the Jill Robert’s Institute for Research in Inflammatory Bowel Disease (JRI). My current lab has a really strong translational side, which really drew me to the lab. My PI (Randy Longman) is a gastroenterologist and as so has a unique patient-focused perspective that shapes the research in the lab, and Randy and the lab are involved in clinical trials, including the use of Fecal Microbiota Transplantation (FMT) to treat Ulcerative colitis patients. Although it’s not my immediate project, an amazing postdoc in the lab is working directly on this project and she's trying to understand the microbial signatures of the responders and non-responders to this type of treatment. The clinic has also just enrolled patients in a new clinical trial involving diet as well, looking at the role of diet and how it applies in different models of colitis in mice, as well as how it impacts the experiences of patients. In sum, my path to where I am currently certainly has not been linear (soil bacteria, to host-pathogen interactions in the lung, to inflammation in the gut) but I’m loving where I have landed at Cornell.

What is your main research project?

There are close to 200 risk loci that have been associated with IBD. The lab has previously shown that one of them, part of the tumor necrosis factor family, TNFSF15 (also known as TL1A) can regulate Type 3 innate lymphoid cells (ILC3s). ILC3s have also been shown by our lab and others to play a role in the pathophysiology of IBD. It is a small population but plays a really big role. Since I started, I’ve been working on extending this investigation, to try to understand the molecular mechanism of how TL1A is regulating ILCs and inflammation. Randy is a consultant for Pfizer and they are in Phase 2 of a clinical trial trying to use anti-TL1A in IBD patients, so we really want to understand the molecular mechanisms of the regulation of TL1A. Shortly after I started, things took a little bit of a turn and I began looking at the role of TL1A in cancer because IBD patients are at higher risk to develop colon cancer, which it's known as colitis- associated cancer. I started using a common colitis-associated cancer model for mice and found that TL1A was playing a role in inducing tumorigenesis. Based on that, my whole project completely changed and now my main focus has been the role of TL1A from inflammation to neoplasia and cancer. It’s a new line or research for the lab and I’m happy to have Randy’s support as I pursue these questions.

What tools and techniques do you use for your research?

We use a lot of genetic deletion or Cre/lox mouse models. One specific example is a mouse line with deletions of DR3, which is a receptor for TL1A, just on ILC3s. For one of my studies I use an Azoxymethane treatment followed by three rounds of colitis (a chronic colitis model). It takes about two months to complete and I have to check the mice every day, so a pretty big time commitment. But mouse models, especially those with specific deletions, are very effective for trying to pinpoint detailed mechanistic pathways. In addition to mouse models, I use FACS (Fluorescence-activated cell sorting) to sort intestinal ILC3s. We are lucky enough to have our own core for FACS in JRI, as well as our own sorter in the lab which is something I use almost daily. The technique is straightforward, but it can be a challenge for my research because intestinal ILC3s are such a small population. Another part of my project is related to neutrophils, so another tool I use is to co-culture ILCs and neutrophils. It’s been an interesting challenge working to develop that line of research.

What resources do you use at Weill Cornell or from the Tri-I?

One thing that blew my mind when I joined were all the opportunities to meet great minds in the immediate area. Here at the Tri-Institute, between meetings, symposiums, and retreats, there are so many opportunities to collaborate. Before Covid I was able to attend the Monday meetings for the immunology program where there are some of the best brains all in the same room. We also have an active collaboration with Gretchen Diehl at MSK, so we have joint lab meetings and share resources as well. I’ve been very impressed by how much interaction there is across labs and I think it’s a smart idea.

In addition, I participated in the professional development series for postdocs this past year and found it very helpful. Even though I’m not on the job market yet, I think it’s important to try and understand what search committees are looking for. It will help me think about if there's something that I can do start doing now. Everyone knows about publication requirements, but there are so many other things that could be helpful for me to begin preparing for. I think it’s great that they provide that series for us.

What are your career plans?

My dream has always been to have my own lab and follow my own research questions. That’s one of the reasons I moved from Columbia to Cornell. I spent three years at Columbia and had published 3 research articles, but the lab was new and the opportunities for independence were limited. Plus, I was interested in switching my research focus from the lung to the gut. Even though I’m now in some ways starting over, which may delay my future plans a bit, I think it was a good move in the long run. We are hoping to submit the project I am working on currently for publication in about one year and along with that I will be applying for grants. Randy knows what my career goals are and is very supportive of me and has been since I first started in the lab. That’s part of the reason he encouraged me to pursue my current project looking at the role of inflammation in colitis-associated cancer. It’s a novel project in the lab so I will be positioned to take it with me when I transition to independence. I know this is a very competitive place, but my dream is to be in New York. As much as I love Portugal, now that I’ve lived in New York for a few years, I never want to leave! I love the city, the science, and the resources – we truly have everything here.

What specifically do you love about New York?

It’s the possibilities. There is just so much of the world in one city. It makes you feel like you can be whoever you want to be. When you walk around, you’ll go from one neighborhood to another and it’s like you're in a different country. I've met people from such different cultures and it’s opened my horizons in a way that I didn't know was possible. Not to mention the food. Portugal is still number one, best food in Europe for me, but here you have everything you could ever imagine. There’s also all the culture. You have Broadway shows, you have theater, you have concerts; I've come across so many artists that I’d never heard of before. It's truly an explosion of culture, delicious food, and different people. There is always the possibility of amazing things that can happen and it just fills me up. My first few months especially, but I’m still in awe to this day.

What is your favorite restaurant in the city?

My friends call me “Burger Queen” because sometimes I just have to have a burger. I have two favorite places: One is the Minetta Tavern and the other is The Warren, both in West Village. The Warren has a great deal on Monday’s where all burgers are $10! Outside of burgers, Numero 28 is really good for pizza. I also have to mention Chinatown – I took some friends visiting from Portugal, and they had been shocked with New York prices, but then I took them to Chinatown where we ate delicious dumplings and everything for like ten dollars. Honestly, it’s hard to choose just one restaurant! But I would say burgers are my thing.

What is the best part about being a postdoc?

The best part is also probably the scariest part, in the sense that you’re on your own. Of course you have your PI, but you don't regularly report to anyone like you did during your PhD. It’s just you and your research. During your PhD you have specific milestones that you have to achieve, which guide your focus a bit more. During your postdoc, you have to find that focus for yourself. You have to be able to follow through on something that is more promising or more valuable in terms of the final end product. So, you have independence to research whatever you want, but you have to be sure to regulate yourself too. A lot of things are amazing in science of course, that’s why we like it, but you have to be able to focus and see what the best route would be for publishing and getting funding. It’s a different mindset from PhD. You have to ask: Is this interesting? Is this important? Is this relevant? Is this fundable? Something I still struggle with is that I find so many things interesting that it can be hard to prioritize what I actually need to learn to benefit my project. Randy has been very helpful while I am learning this. He sees further ahead than I do and he helps guide me in figuring out where the line is between exploration and focusing. Even as I am learning how to focus in, knowing that there is freedom in which research questions I can pursue has really solidified me wanting to run my own lab someday.

What was your experience participating in the 2020 Postdoc Research Day?

I was in my first year here at Cornell when I participated, and I had the best time. What I presented was the beginning of my current project. We had some preliminary data from our mouse model of colitis- associated cancer showing correlations between TL1A, inflammation and cancer, which have now been maintained with additional research as well. I was a little nervous because it was my first presentation here and although I had some data, I was still building a story and there were more questions than answers. Overall, it went well though. Even with the Covid restrictions it was well organized, and I really liked the experience. It was interesting hearing about other postdoc’s research. I see other postdocs come and go in the hallways or the mouse housing areas, but usually have no idea what anyone else is doing for research. It’s cool to have a day dedicated to postdocs, where we can talk about our research and get to know each other.

What advice would you share with new postdocs?

Don't be afraid of getting out of your comfort zone. I think changing is good and can really pay off. Getting out of your comfort zone can give you a unique perspective because you have different ways of looking at things by applying the breadth of what you’ve learned. The transition from PhD to postdoc can be overwhelming because you get to a new lab and you just want to show what you can do, but at the same time the lab environment can be really different and you have to adapt. It helps to remember that in your PhD you learned how to think and how to learn new things. So, I would definitely say don’t be afraid of getting out of your comfort zone and don’t be afraid of asking people if they know something you’d like to know – they can really help you out.

I would also tell all postdocs to try and get the most of each day outside of lab. It’s a given that you have to come into to the lab. For me, because of the mouse models I use, I actually have to come in every day. But I make an effort to get here early, get my work done, and then go out to enjoy the city. That’s something I learned at Columbia during my first year when I was practically living in the lab. Sure, sometimes you have to do that when a big deadline is coming up. But you also have to give yourself a break when you can. I have a lot of my best ideas when I’m taking a break – things will come to me that I’d never thought about before. So, prioritize – focus on the essential tasks and what you really need to get done each day and then try to remind yourself not to start additional tasks that will keep you there for much longer. We all work hard every day so things will work out and everything will get done in the long run. Life is a multitude of things. Science is a big part, but you have to enjoy other things as well.