Background

Yifeng was born in Ziyang, a little town outside Chengdu, Sichuan. As the only child of Xiaoju Chen and Nu Zhang, Yifeng grew up following her mother around in the hospital and took full advantage of her dad’s toolbox (R.I.P. to all the delicate parts and electronics), which fostered her healthy devotion to taking things apart. Meanwhile, Yifeng had been introduced to the Neverland of creative writing way before she could even figure out how to ask unceasing “why” questions to the extent that it was almost a surprise when she chose sciences over humanities in high school.

True to her eccentric nature, Yifeng made her way across the Pacific Ocean to the center of the cornfields to attend Luther College, to study Biology and Management initially (to reassure her parents that she would have a job at the end of college). The liberal arts education gave her the freedom to take classes that a biologist did not necessarily need, from “Religion and Science” to “The Philosophy of Science” and from “Art History” to “Filmmaking.” Eventually, she realized that she could not stare at accounting sheets 24/7. Instead, it became evident that she could and will happily sit in front of benches and solve experimental problems for extended periods.

It was a capricious decision fueled by curiosity to reach out to her academic advisor seeking research exposure, which led her to the laboratory of Dr. Linda McCarter for a short research internship in the winter of 2015. She was introduced to the magical world of microbial genetics and bacterial physiology by studying bacterial surface sensing and swarming motility differentiation. She then participated in the NSF Research Experience for Undergraduates in 2015 and returned to the McCarter lab the following year. This priceless research experience ultimately inspired Yifeng to pursue graduate school. In the Spring of 2018, she joined the laboratory of Dr. Lilliana Radoshevich, where she discovered the enchanting world of host-pathogen interactions and began to study the conjugation-dependent antibacterial mechanisms of ISG15. At times, she has been sighted jumping up and down and/or making squeaky noises in the lab, primarily driven by what she managed to find under the microscope.

Outside of the lab, Yifeng is an avid dancer. She particularly enjoys this form of non-verbal yet universal communication and expression. When not in the lab or dancing, she can be found staring at bonfires, chasing birds, touching animals that perhaps shouldn’t be touched, carving, reading out of spite, collecting plants impulsively, feeding pets, obsessively playing the violin, playing video games, or binge-watching TV series. In addition, she loves drinking coffee and annoying her cat(s). If you manage to get her tipsy, you will be greeted with endless philosophical questions such as “How do you know what you know is true?” and “What does it mean to be a human?”.  10/10 would recommend it.

Research

Listeria monocytogenes is a ubiquitous bacterium with a highly adaptable lifestyle that can be commonly found in the soil and decaying vegetation. It is an opportunistic foodborne pathogen causing listeriosis, a rare but often fatal infection, particularly in high-risk populations, such as pregnant individuals, infants, the immunocompromised, and the elderly. The CDC estimates that 1600 people get sick and about 260 people die from L. monocytogenes infection each year, making it the third leading cause of death from food poisoning in the United States.

The high lethality of L. monocytogenes infection is due to the pathogen’s ability to survive various harsh defense strategies from the mammalian host. Interferon stimulated gene 15 (ISG15) is one of those effectors massively produced by the host when L. monocytogenes is detected in the cytosol. Following induction, ISG15 can covalently modify intracellular proteins through a regulated enzymatic cascade ISG15 is required to confer host protection against L. monocytogenes in a conjugation-dependent manner. However, the consequence of ISGylation during L. monocytogenes infection is poorly defined. 

My thesis focuses on understanding the conjugation-dependent mechanisms by which ISG15 protects the host from L. monocytogenes. We have identified endogenous ISG15 substrates following L. monocytogenes infection previously. My work has built on those findings and validated that ISG15 modifies key regulators of autophagy as well as critical proteins of the actin polymerization machinery. When properly regulated, this serves as a host defense strategy to restrict bacterial growth and dissemination. However, dysregulated ISGylation of actin polymerization machinery is exploited by L. monocytogenes, resulting in increased host mortality. Taken together, my work adds to our mechanistic understanding of how ISGylation facilitates bacterial clearance and inhibits pathogen dissemination. Additionally, our findings emphasize the proper regulation of ISGylation in the efficacious control of bacterial infections.