On July 6. 2022, Shaowen White successfully defended his thesis titled, "HSV cVAC as a Tool for Viral Egress Research and Therapeutic Development”. He is pictured with his mentor Richard Roller, PhD.
About Shaowen
Shaowen was born in Chengdu, Sichuan, PRC, to Keqin Xu and Junru Li. Evidence suggests he is a distant relative to V. K. Wellington Koo, one of the United Nations founders. Shaowen was interested in zoology during his childhood and enjoyed raising small animals such as tropical fish, skinks, and amphibians. At the time, he wished to become a zoologist or a veterinarian. A parent's friend mistakenly reckoned that Shaowen was interested in medical sciences and invited him to visit the West China Medical Center, Sichuan University's cadaver museum, and observe a cadaver dissection class for senior medical students. Shaowen was ten years old and was traumatized by this experience, but he also realized that medicine and zoology are fundamentally the same.
During high school, Shaowen found himself lacking the academic prowess of his father's side of the family or the artistic talent of his mother's side. Eventually, he went to Suzhou College of Medicine, Soochow University, and studied pharmacy/pharmaceutics. At Soochow University, Shaowen tried to figure out his place in the world by trying various activities. He experienced a little bit of a clinical practitioner's life and was overwhelmed. He worked as a volunteer in an animal rescuing facility and learned a new musical instrument – the accordion. He also served as the co-president of Ju Yue Fang and Mayflower music club, the latter being the largest student organization in the medical college. Most importantly, he had his first research experience in Dr. Jianwen Wang's lab studying polysaccharides in bamboo pathogen Shiraia bambusicola.
Two years after studying at Soochow University, Shaowen was given an unexpected opportunity to migrate to the Midwest, USA, at the cost of giving up his original life plan. Shaowen took the plunge and came to the land of scientific innovations. He enrolled at the Grand Valley State University in Allendale, Michigan, where he joined the Old World Music club as an accordionist. While at the university, he worked in Dr. M. Aaron Baxter's lab screening for oxygen sensors that regulate E. coli biofilm and for regulators of Salmonella pathogenicity island I. This research experience inspired Shaowen to study microbiology. He applied to the University of Iowa hoping to study bacterial pathogens, but after meeting Dr. Rich Roller, he decided to delve into herpesvirus research. After all, they are all intracellular pathogens and their genomes DNA. If Shaowen manages to pass his defense, he will move on to a postdoc position at Brigham and Women's Hospital in Benjamin Gewurz's lab, studying a different herpesvirus – Epstein-Barr virus.
Outside academic life, Shaowen hangs out with friends, plays accordion, and collects graphic novels. His top three manga series are Blame! (by T. Nihei), Fire Punch (by T. Fujimoto), and Claymore (by N. Yagi).
Research
Herpes Simplex Virus (HSV) is a ubiquitous virus that infects 40%-90% of the global population and is a leading cause of blindness and encephalitis. Herpes simplex encephalitis has a mortality rate of 70%, which is caused by the spread of HSV lytic infection in the brain. The only treatment for HSV infections currently is acyclovir and its derivatives, which all target a single mechanism–viral DNA replication. This lack of alternative therapeutics has led to the emergence of drug resistant HSV.
Meanwhile, the cytoplasmic assembly of HSV is a process that contains ample druggable targets. As a large enveloped virus, each HSV virion incorporates more than 12 glycoproteins (mostly transmembrane proteins) and as many as 23 tegument proteins (some membrane- associated proteins). Disrupting the function of any one of these structural proteins typically results in aborted or attenuated infections in vivo. However, the function of many of these proteins, and how are they transported together for viral assembly are poorly understood. Especially, the nature of membranes that are required for HSV assembly, and how are they formed, are either controversial and elusive. The difficulty in the study of the HSV cytoplasmic assembly stems from the cell model: in commonly used cancerous or epithelial cells, host organelles are drastically modified, which makes it difficult to (i) imply the function of these membranes based on their identities in uninfected cells, and (ii) identify organelles under ultrastructural analysis.
My works described HSV rearrangement of host membranes in a cell type-dependent manner and the formation a unitary cytoplasmic viral assembly center (cVAC) in infected neuronal cells. The cVAC provides a visual landmark to distinguish vesicles that are directly involved in HSV assembly. By using the HSV cVAC as a tool, my works revealed mechanistic details of HSV assembly that cannot be addressed by epithelial cell models, including a nocodazole-resistant tethering between organelles in infected cells. Building on these discoveries, a novel interaction between HSV spreading factor pUL51 and a host motor protein was discovered. Finally, my works showed that this interaction can be targeted to inhibit HSV spread in cell cultures.