Trained as a dentist and microbiologist, Dr. Xuesong He started his academic career by studying bacterial pathogenicity at the single species and duo-species level. 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 decade, 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. The following are some of the research interests in Dr. He’s laboratory.
1) Achieving better understanding of host associated microbial ‘dark matter’
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. His team shed light on the unique epibiotic/parasitic lifestyle of TM7. Furthermore, TM7 belongs to Candidate Phyla Radiation (CPR), a class of bacteria recently revealed by metagenomics-based approach and estimated to account for over a quarter of microbial diversity. Thus far, TM7x and its bacterial host remain the best studied model system in understanding CPR’s “mysterious” lifestyle and their unique biology.
2) Understanding the ecological and social aspects of the microbial community. 3) Investigating the role of host-tRNA derived small RNA (tsRNA) in modulating host-microbial interaction; 4) Developing novel approaches, such as acid-activated antimicrobials and probiotic-based microbial modulation, in combating dental caries, and 5) Understanding the interactions bridging the microbiome (gut and/or oral) and other systemic conditions, such as gut-bone axis. Dr. He is the contact PI of multiple active R01 grants from NIH. The national and international impact of Dr. He’s research can be proved by his over 80 well-cited publications in peer-reviewed leading scientific journals including PNAS, ISME J, Cell Reports, Cell Host & Microbe, Trends in Microbiology, Journal of Endodontics, PLOS Pathogens, and Journal of Dental Research.
The following are some of the related news links:
Dr. He’s research in this area was 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.
This project is currently supported by a renewed 5-year R01 grant from NIDCR.
2). 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 is particularly interested in understanding the role of host tRNA-derived small RNAs (tsRNAs) in modulating host-microbial interactions.
Dr. He’s team was recently awarded a new R01 grant to specifically study the cross-kingdom trafficking of host generated sRNA in mediating the microbial host interaction.
3) Developing novel antimicrobials in preventing dental caries
Trained as a dentist, one of the ultimate goals of Dr. He’s research is to develop novel and effective preventative/therapeutic strategy in fighting dental caries/periodontal diseases. Collaborating with his colleague, Dr. Jirun Sun, a material scientist at Forsyth, Dr. He has been actively involved in developing novel antimicrobials, such as acid-activated antimicrobial compounds, in preventing dental caries by targeted removal of cariogenic bacteria.
Dr. He is currently the Co-PI of an active NIDCR-funded R01 project. The goal of this research is to prevent dental caries through targeted treatment of acid-producing bacteria (t-TAB). t-TAB will promote a healthy microbial community that is vital for modulating pH and preventing acid-induced teeth damage. The t-TAB will be achieved by selectively inhibiting the growth of cariogenic bacteria
4) Host microbiome-related research areas
A. It has been greatly appreciated that host associated microbiome plays a critical role in the regulation of various physiological and pathological processes of the human body and are associated with various diseases. Thus, understanding the interaction bridging the microbiome (gut and/or oral) and other systemic conditions is of great clinical significance. The following are the two collaborative projects Dr. He is actively establishing:
- Understand the bidirectional interactions bridging the gut-bone axis (with Dr. Yingzi Yang at HSDM)
- Investigate the role of gut/oral microbiome in maintaining the homeostasis of the salivary gland function (with Dr. Qing Yu at Forsyth)
B. Probiotic-based microbiome modulation has attracted increasing attention in preventing/treating human polymicrobial diseases. Nature might have already provided best probiotic microbial species hidden among healthy microbiome and play crucial role in maintaining microbial-host homeostasis. The key is how we can systemically identify those probiotic candidates. The following is the collaborative project Dr. He is actively developing:
- To integrate a computational framework based on community ecology and network science, in vitro experiments, and analysis of published data from in vivo human oral microbiome studies to test the hypothesis that representing the human oral microbiome as an ecological network allows us to systematically identify candidate probiotics that can prevent oral diseases, such as dental caries and periodontal diseases (with Dr. Yang-Yu Liu at HMS).