My journey investigating the innate immune response to intestinal infection

Looking back on 2022, I can only say that this past year was filled with a lot of firsts. I experienced my first uninterrupted year of in-person classes, and I had the opportunity to work in a lab as an undergraduate researcher in the Cobo lab, under the guidance of Dr. Eduardo Cobo. Through this experience, I contributed to my first peer-reviewed publication, which focused on investigating the innate immune response of neonatal calves to intestinal infection. The long-term goal of my research is to explore why newborn humans and other mammals are so susceptible to intestinal pathogens, with a desired outcome of improving health outcomes. My research also involves work with mice, exploring how animals that have developed immunity respond to intestinal pathogens, such as E. coli.

It's worth noting that only four decades ago, infectious diarrhea was responsible for 4.6 million deaths annually. However, this mortality has been reduced to 2.1 million through increased sanitation and research into the etiology of infectious diarrheas. My current research in the Cobo lab is aimed at understanding how a host’s immune response can contribute to the severity of infectious diarrhea, possibly increasing diarrhea-related mortalities or morbidities.

As a part of the innate immune response, a series of proteases (which are protein cleaving enzymes) are released during infection. Using bulk RNA-sequencing, we found that a family of endogenous proteases known as matrix metalloproteases (MMPs) were increased in mice infected with C. rodentium, a pathogen which models E. coli infection in humans. Importantly, MMPs are involved in both normal and diseases states, highlighting the important of balance in the immune response. Using single cell RNA sequencing, our lab is working towards describing the mechanism by which MMP-2 and -9 are involved in an important inflammatory pathway, i.e., the reactive oxygen species immune response, during intestinal infection. Our goal for the near future is to inhibit the activity of MMP-2 and -9 to see if a decrease in diarrhea and a decrease in intestinal damage will occur.

Once again, 2022 was a year of growth and learning, both academically and personally, I am grateful for all the opportunities that my mentor and PI Dr. Cobo has given me, and I am looking forward to continuing with research in the future.