Felipe Santiago-Tirado is an Assistant Professor from the Department of Biological Sciences and is an affiliate of the Eck Institute for Global Health. Santiago-Tirado has a PhD from Cornell University and a BS from the University of Puerto Rico. In this spotlight, Professor Santiago-Tirado talks about his research on Cryptococcus neoformans and other fungal pathogens, his doctoral work that sparked his interest in infectious diseases, and his experiences so far at Notre Dame.
Q. Tell us about your research project. In what ways have your personal experiences shaped your area of interest?
A. I work with fungal pathogens, specifically the ones that cause serious human disease. Human fungal diseases range from minor skin and mucous membrane infections to invasive, lethal diseases. Ironically, the last type of infection tends to be neglected and unappreciated by the general public, especially in developed nations. Even I failed to grasp the seriousness of fungal infections as I was growing up and completing my undergraduate and graduate studies. Collectively, they kill over 1.6 million people every year, and the main culprits are the yeasts Cryptococcus and Candida, which are the two fungi that we work with in the lab. So if you ask if I have any personal experience that has shaped my research, I thankfully have never suffered from a fungal infection, but I understand the lack of awareness that exists in society, hence one of the drivers of my research is the need to highlight the importance of fungal infections and increase awareness of these lethal fungal infections.
Cryptococcus neoformans is a ubiquitous environmental fungus, so we are exposed to it frequently. We inhale it and if we are healthy, we can control and clear the infection. However, if we are immunocompromised in any way, the infection progresses and disseminates from our lungs to the brain, causing a lethal meningoencephalitis that is invariably fatal if untreated, and even with treatment, it is associated with a mortality of 20 – 80%, depending on the region. With this fungus, my primary research goals are to understand how it can survive inside host phagocytes and cross cellular barriers, which are the main drivers of disease progression. I am also interested in the unique cell biology of this fungus, such as its ability to secrete a polysaccharide capsule, offering the potential of novel therapeutic targets, as well as uncovering basic biology applicable to other pathogens. My other project is a collaboration with Dr. Flores-Mireles' lab, trying to understand the catheter-associated urinary infections (CAUTI) caused by fungus Candida albicans. This fungus has become the second most common cause of CAUTI, and little is known about the mechanisms the fungus uses to cause disease. Together with the Flores-Mireles lab we are dissecting these mechanisms with the hope to find potential points of intervention to either prevent or treat these infections.
Q. What do you think are your most significant research accomplishments to date?
A. I have not always worked with fungal pathogens, so it is hard for me to pick a story in just my current research. I am very proud of my doctoral work where I found and described a mechanism that cells use to polarize, in other words, to orient themselves in time and space. It is very important for cells to know what’s up, what’s down, or when to deliver cargo to a specific area of the cell. Cells use various mechanisms to do that, and I described one called “coincidence detection” and it turned out, that multiple pathogens also use that same mechanism to infect cells. Actually, that discovery sparked my interest in infectious diseases, and it is the reason I started working with fungal infections. After I started working with fungi, I would say that my work showing how Cryptococcus enters the brain (or at least one of the ways), as a passenger inside host immune cells through a process called “Trojan horse transit”, is one of my most important accomplishments.
Q. What do you find to be the most rewarding aspect of training students?
A. To see them smile and be happy when the experiment works. To see them accomplish milestones like publishing a paper or getting a grant or an award. Seeing them succeed is plain and simple the most rewarding aspect. For example, I have a drawer full of thank you notes from past undergrads that have gotten into medical school or grad school. Every time I receive one it just makes my day. Many of them are so much more motivated and smarter than I was at their stage, so I’m sure that they will become superstars in whatever they end up doing. If I can help them achieve that, that is already a big reward in my book!
Q. What is your favorite thing about the University of Notre Dame?
A. I like the emphasis on student wellbeing. Students here, undergrad and grads alike, are happy for the most part. Compared to other places I have been, Notre Dame really takes care of their students. Working with happy students makes my work even more enjoyable and rewarding. I also like the awareness the administration has about working parents, especially about families where both parents are faculty, which makes it a bit easier to find a work-home balance.
Q. What are your plans for the future? What do you hope to accomplish with your current projects?
A. You are asking a relatively new professor, so I have to say to obtain tenure! I already enjoy teaching and have a nice research group established, so I need to publish, get grants, and get tenure. I hope to become the best mentor and colleague I can be, and give my students a good and rewarding research experience. And lastly, I hope that through my research, I can get people to think about fungi, and increase the awareness of fungal infections. Everybody knows viruses and bacteria are deadly, but when I ask my undergrad students about a fungal disease, invariably they say “athlete’s foot.” Increasing awareness about fungal diseases will result in more funding and thus, more research, bringing us closer to better therapeutics or, even better, prevention.
Originally published by at globalhealth.nd.edu on September 30, 2022.