Yuan Laboratory: Research Interests

Dr. Yuan’s lab studies the interactions between enteric viruses and the host immune system. The lab's research interests are focused on pathogenesis and innate and adaptive immune responses induced by enteric viruses (i.e. norovirus and rotavirus) and on the development of safer and more effective vaccines against viral gastroenteritis.

One of the major research efforts of the Yuan lab is to study mechanisms of immune modulation by probiotic bacteria, prebiotics (rice bran) and human gut microbiota in rotavirus and norovirus infection and vaccination. These studies utilize wild type, gene knock-out and humanized gnotobiotic pig models of human rotavirus and norovirus infection and diseases and IPEC-J2 cell culture model of rotavirus infection.

Dr. Yuan has a long-standing interest in enteric viral vaccines. She has studied intestinal and systemic immune responses induced by various rotavirus and norovirus vaccines and their protective efficacy against the viral infections and diarrhea. These studies have included attenuated, reassortant, inactivated, recombinant protein (P2-VP8*), DNA plasmid, virus-like particle, and P particle vaccines, with different adjuvants (Alum, LT-R192G, ISCOM, MPL, chitosan, rice bran and probiotics) and immunization routes (oral, intramuscular, intranasal, intradermal by gene gun) with or without maternal immunomodulators (antibodies and cytokines). Currently, the Yuan lab is evaluating the immunogenicity and protective efficacy of an RNActive®-based VP8* rotavirus vaccine.

Another research area in the Yuan lab is to establish a reliable gnotobiotic pig model of human enterovirus 71 infection and disease, and to use the animal model to evaluate human enterovirus 71 vaccines and anti-viral drugs.

Dr. Yuan's research projects have been funded by National Center for Complimentary and Alternative Medicine, National Institutes of Health (R01AT004789); the National Institute of Allergy and Infectious Diseases, National Institutes of Health (R01AI089634 subcontract); PATH (Program for Appropriate Technology in Health); Bill & Melinda Gates Foundation (Grand Challenges Explorations Phase I and Phase II); Lanzhou Institute of Biological Products, China; and CureVac GmbH, Germany.

Select a research interest below for more details.

Rotavirus Research

Rotaviruses belong to the Reoviridae family, which possess a segmented double-stranded RNA genome.

Rotaviruses infect and replicate in the villous enterocytes of the small intestine, causing structural and functional changes of the intestinal epithelium and diarrhea.

Rotavirus infection is the most common cause of severe viral gastroenteritis in children under 5 years of age in the United States, leading to a tremendous disease burden with costs to health care and society exceeding one billion dollars annually. Rotavirus causes even more immense morbidities and mortalities in developing countries.

Vaccination is recognized as the only control measure having a significant impact on the incidence of rotavirus gastroenteritis and is considered the first-line strategy for disease prevention. However, the current vaccines only provide 30-42% protection rate against rotavirus gastroenteritis in the poorest Asian and African countries where rotaviruses cause the highest numbers of mortality among the estimated 527,000 deaths due to rotavirus infection globally each year.

The knowledge generated by our studies will provide new strategies and methods to effectively modulate the immunological processes involved in rotavirus infection/vaccination, thus enhancing the immunogenicity and protective efficacy of rotavirus vaccines.

Norovirus Research

Noroviruses (NoVs) are single-stranded, positive-sense RNA viruses belonging to the Caliciviridae family. NoVs cause >90% of non-bacterial epidemic acute gastroenteritis, affecting people of all ages worldwide. In children, NoV is the second most important etiological agent (next to rotavirus) causing dehydrating diarrhea.

The symptoms of NoV infection in humans are sudden onset and frequent vomiting and diarrhea that often lead to dehydration. NoV infections cause an estimated ~23 million cases of acute gastroenteritis each year in the United States alone.

Noroviruses are highly contagious and can be spread quickly by person-to-person transmission, through contact with contaminated environmental surfaces, or by contaminated food and water, which are common sources of large outbreaks in a variety of settings. These outbreaks are especially prevalent in semi-closed communities, such as hospitals, cruise ships, nursing homes, the military and schools.

Human NoVs remain difficult to study because of the lack of appropriate cell culture and small animal models and the NoV disease is difficult to control because of the wide spread nature and the lack of effective treatment and prevention methods. In addition, the potential threat by bioterrorism with NoVs increases the need for an effective vaccine against NoVs.

The Yuan lab is conducting natural history studies of currently circulating human noroviruses in gnotobiotic pigs to establish the gnotobiotic pig model of human norovirus infection and disease. The animal model will be used to characterize the safety, immunogenicity and broadness of candidate norovirus P particle vaccines in protection against various noroviruses.

Probiotics Research

The current FAO/WHO definition of probiotics is: “live microorganisms, which, when administered in adequate amounts, confer a health benefit on the host.” Stimulation or improvement of the immune system is a mode of action by which probiotic lactobacilli exerts a beneficial effect to the host.

Adjuvanticity of lactobacilli in enhancing cellular and humoral immune responses has been reported in studies of influenza, polio, and rotavirus vaccines, and rotavirus and Salmonella typhi infections. The immunomodulating mechanism exerted by probiotics is still not fully understood and so is one of the targets of Dr. Yuan’s research.

Studies have indicated that many facets of the immune system are influenced, including increased IgA antibody production; induction of cytokine synthesis; activation of monocytes, macrophages, and dendritic cells; and regulation of the balance of Th1, Th2 and regulatory T cells.

Different probiotic bacteria strains at different doses have different stimulatory and regulatory effects based on different immune status of the host. Further studies are underway in the Yuan lab to clarify the mechanisms of lactobacilli’s immunostimulating effect on rotavirus vaccines in neonatal gnotobiotic pigs.