Xuesong He, PhD, DDS

Forsyth Profile — audio interview

Trained as a dentist, Dr. Xuesong He started his academic career by studying bacterial pathogenicity at the single species and duo-species level. Dr. He made significant contributions towards the better understanding of the regulation of virulence factors in some of the main oral pathogens, including the cariogenic bacterium Streptococcus mutans, and periodontal pathogen, Fusobacterium nucleatum.

In the past few years, with the explosion of our knowledge in the diversity and complexity of host-associated microbiome, as well as the increased appreciation of their crucial role in human health, Dr. He has expanded his research interests to tackle the new challenges in the host-associated microbiome, particularly oral microbiome research.

Research:

1). “Domestication of yet-to-be cultured microbes”

One of the biggest challenges in oral microbial research is to culture those yet-to-be cultured species for detailed physiological/pathogenic analysis.  By using a novel culturing method, Dr. He’s team successfully isolated and cultivated from the oral cavity the first TM7 strain (named TM7x), which belongs to TM7, a bacterial phylum that is omnipresent, particularly in the human oral cavity, and associated with periodontal disease. They also revealed its unique epibiotic/parasitic lifestyle with its bacterial hosts. Furthermore, TM7 belongs to Candidate Phyla Radiation (CPR), a unique class of bacteria recently revealed by metagemonics-based approach. Thus far, TM7 remains the only phylum with cultivated representatives in the CPR group. This study has received media attention through joint press releases involving NIDCR. The following are some of the related news links:

Dr. He’s study in this area was recently highlighted in a NIH review, titled “A review of 10 years of human microbiome research activities at the US National Institutes of Health, Fiscal Year 2007-2016”, published in a Feb. 2019 issue of Microbiome.

Currently, Dr. He’s team is using TM7x and their bacterial host as a model system to further study their unique lifestyle, their ecological impact, as well their role in host health and diseases. The knowledge gained will be fundamental in better understanding other CPR bacteria, which make up >25% of the bacterial domain.

2). “Understanding the social structure and community functionality of host-associated microbiome”

It is well established that the host-associated microbiome interferes with the colonization of microbes of foreign origins, a phenomenon referred to as colonization resistance. However, due to the complexity of the host-associated microbiota, it has been extremely difficult to elucidate the community colonization resistance mechanisms. Using an in vitro multispecies model system, Dr. He’s team revealed for the first time the sophisticated structure and functional organization of a colonization resistance pathway within a microbial community, providing evidence of the social functionality within microbial community. Several papers published on this topic were highlighted in a Science perspective article (Fredrickson JK. 2015. Science 348 (6242):1425). They are currently using a comprehensive multi-omics approach to reveal the detailed mechanisms governing this intriguing and ecologically relevant phenomenon.

3). “Studying the ecological importance of individual bacterial species within host-associated microbiome”

Another major challenge to studying the human microbiome and its associated diseases is the lack of effective tools to achieve targeted modulation of individual species to study their ecological function within multispecies communities. Dr. He’s team was the first to develop a proof of concept that it is possible to examine the ecological importance of individual species within a complex microbial community by knocking out or knocking down one particular species with a targeted antimicrobial and then tracking the impact on the rest of the species within the same community. Using a specifically targeted antimicrobial peptide against human cariogenic S. mutans, they showed targeted killing of S. mutans within an in vitro oral multispecies community, and the drastic reconstruction of the microbial structure following its removal.

The research has received media attention through joint press release. The following are some of the related news links:

Currently, using this approach, Dr. He’s team is in the process of identifying and studying “keystone” species whose removal could result in the collapse of the normal community structure and have significant impact on community functionality.

4). “Microbial-Host Interaction”

Coevolution of the human host and its associated microbiota has led to sophisticated interactions to maintain a delicate homeostasis. Emerging evidence suggests that in addition to small molecules, peptides, and proteins, small regulatory noncoding RNAs (sRNAs) might play an important role in cross-domain interactions. Dr. He’s team is particularly interested in understanding the role of host tRNA-derived small RNAs in modulating host-microbial interactions.

Teaching:

While focusing on research, Dr. He also enjoys opportunity to teach courses and mentor students and researchers over the years. Teaching has always been a pleasant experience for him. Since Dr. He joined the Forsyth Institute, he has been actively involved in giving lectures, including OB601, an oral microbiology course for Advanced Graduate Education Students offered at Harvard School of Dental Medicine; and AdvOB, an advance course in oral biology for graduate students in Boston University.

Dr. He’s long-term goal is to continue his research on the forefront of oral microbiology. He aims to achieve comprehensive and systemic understanding of the oral microbiome and its impact on human health by integrating culture-independent multispecies multi-omics analysis and culture-dependent microbial-host physiological/pathogenic study. Meanwhile, he will continue to contribute to graduate programs at the Harvard School of Dental Medicine by giving lectures related to his fields of expertise.


Background

Beijing University, School of Dental Medicine, Beijing, China, DDS, 1997, Dental Science
Indiana University, Bloomington, IN, PhD. 2006, Microbiology
UCLA School of Dentistry, Los Angeles, CA, Postdoc, 2006-2010, Oral Microbiology