Yiping W. Han, Ph.D.
Professor of Microbial Sciences in Dental Medicine and Microbiology & Immunology
Ph.D., University of Illinois - Urbana
Host-pathogen interactions, human microbiome, oral-systemic connections
The human microbiome is a vast population of microbes that inhabit various surfaces of the body, and plays an essential role in health and disease. We are interested in the interactions of these microbes and their human hosts, and work in our laboratory encompass the following areas:
1. Investigating the role of oral bacteria in extra-oral infection and inflammation. Increasing evidence suggests that microbial communities specific to particular regions of the body are not isolated from each other, but rather, are mobile and interchangeable. For example, oral bacteria are not limited to the confines of the mouth and are frequently detected at extra-oral sites associated with infections and inflammation. Using culture-independent technology, we investigate the impact of the oral microbiome on pregnancy complications and gastrointestinal (GI) disorders.
2. Investigating the mechanisms of Fusobacterium nucleatum pathogenesis in pregnancy complications and GI cancer. F. nucleatum is a gram-negative anaerobic oral commensal prevalent in pregnancy complications including preterm birth, stillbirth and neonatal sepsis. It has also been associated with GI disorders, including inflammatory bowel disease, colorectal and esophageal cancers and appendicitis. Using in vitro and in vivo model systems, we investigate the mechanism of F. nucleatum in pregnancy complications and GI cancers. We have identified a unique adhesin, FadA, from F. nucleatum that plays an essential virulent role. FadA is thus a potential diagnostic and therapeutic target for disease detection and prevention. Our studies on FadA include continued analysis of its structure, function and regulation, as well as investigation of its clinical relevance in patient cohorts.
3. Developing genetic tools for mutant construction in bacteria. Studies of microbes are often hindered by the lack of genetic tools. Our lab was the first to utilize ultrasound to facilitate DNA delivery (sonoporation) into bacteria, and we constructed the first double-crossover allelic exchange mutant in F. nucleatum. Developing bacterial genetic tools continues to be a focus in our lab.
Rubinstein, M.R., Baik, J.E., Lagana, S.M., Han, R.P., Raab, W.J., Sahoo, D., Dalerba, P., Wang, T.C. and Han, Y.W. (2019) Fusobacterium nucleatum promotes colorectal cancer through induction of novel Wnt/b-catenin modulator Annexin A1 in proliferating cancerous cells. EMBO Reports doi.org/10.15252/embo.201847638.1. Press release: https://www.dental.columbia.edu/news/how-common-oral-bacteria-makes-colon-cancer-more-deadly
Garcia-So, J., Zhang, X., Yang, X., Rubinstein, M.R., Mao, D.Y., Kitajewski, J, Liu, K. and Han, Y.W. (2019) Omega-3 fatty acids suppress Fusobacterium nucleatum-induced placental inflammation originating from maternal endothelial cells. JCI Insight 4: e125436. doi.org/10.1172/jci.insight.125436. Press release: https://www.dental.columbia.edu/news/could-omega-3-fatty-acids-help-prevent-miscarriages
Vander Haar, E.L., So, J., Gyamfi-Bannerman, C. and Han, Y.W. (2018) Fusobacterium nucleatum and adverse pregnancy outcomes: Epidemiological and mechanistic evidence. Anaerobe 50: 55-59.
Han, Y.W. (2015) Fusobacterium nucleatum: a commensal-turned pathogen. Curr. Opin. Microbiol. 23C:141-147.
Han, Y.W. (2014) Oral bacteria as drivers for colorectal cancer. J. Periodontol. 85: 1155-1157.
Rubinstein, M.R., Wang, Y., Liu, W., Hao, Y., Cai, G. and Han, Y.W. (2013) Fusobacterium nucleatum promotes colorectal carcinogenesis by modulating E-cadherin/beta-catenin signaling via its FadA adhesin. Cell Host & Microbe 14: 195-206.
Han, Y.W. and Wang, X. (2013) Mobile microbiome: oral bacteria in extra-oral infections and inflammation. J. Dent. Res. 92: 485-491.
Fardini, Y., Wang, X., Temoin, S., Nithianantham, S., Lee, D., Shoham, M. and Han Y.W. (2011) Fusobacterium nucleatum adhesin FadA binds vascular-endothelial cadherin and impairs endothelial integrity. Mol. Microbiol. 82: 1468-1480.
Han, Y.W. (2011) Can oral bacteria cause pregnancy complications? Women's Health 7: 401-404.
Han, Y.W. (2011) Oral health and adverse pregnancy outcomes – what's next? J. Dent. Res. 90: 289-293.
Fardini, Y., Chung, P., Joshi, N. and Han, Y.W. (2010) Transmission of diverse oral bacteria to murine placenta: evidence of oral microbiome as a source of intrauterine infection. Infect. Immun. 78: 1789-1796.
Han, Y.W., Fardini, Y., Chen, C., Iacampo, K.G., Peraino, V.A., Shamonki, J.M. and Redline, R.W. (2010) Term stillbirth caused by oral Fusobacterium nucleatum. Obstet. Gynecol. 115: 442-445.
Ikegami, A., Chung, P. and Han, Y.W. (2009) Complementation of the fadA mutation in Fusobacterium nucleatum demonstrates that the surface-exposed adhesin promotes cellular invasion and placental colonization. Infect. Immun. 77: 3075-3079.
Han, Y.W., Shen, T., Chung, P., Buhimschi, I.A. and Buhimschi, C.S. (2009) Uncultivated bacteria as etiologic agents of intra-amniotic inflammation leading to preterm birth. J. Clin. Microbiol. 47: 38-47.
Nithianantham, S., Xu, M., Ikegami, A., Yamada, M., Shoham, M. and Han, Y W. (2009) Crystal structure of FadA adhesin from Fusobacterium nucleatum reveals a novel oligomerization motif, the leucine chain. J. Biol. Chem. 284: 3865-3872.
Xu, M., Yamada, M., Li, M., and Chen, S.G. and Han, Y.W. (2007) FadA from Fusobacterium nucleatum utilizes both secreted and nonsecreted forms for functional oligomerization for attachment and invasion of host cells. J. Biol. Chem. 282: 25000-25009.
Liu, H., Redline, R. and Han, Y.W. (2007) Fusobacterium nucleatum induces fetal death in mice via stimulation of TLR4-mediated placental inflammatory response. J. Immunol. 179: 2501-2508.
Han, Y.W., Ikegami, A., Chung, P., Zhang, L., Zhou, Y. and Deng, D.X. (2007) Sonoporation is an efficient tool for intracellular fluorescent dextran delivery and one-step double-crossover mutant construction in Fusobacterium nucleatum. Appl. Environ. Microbiol. 73: 3677-3683.
Han, Y.W., Ikegami, A., Bissada, N., Herbst, M., Redline, R.W. and Ashmead, G.G. (2006) Transmission of an uncultivated Bergeyella strain from the oral cavity to amniotic fluid in a case of preterm birth. J. Clin. Microbiol. 44: 1475-1483.
Han, Y.W., Ikegami, A., Rajanna, C, Kawsar, H.I., Zhou. Y., Li, M., Sojar, H., Genco, R.J., Kuramitsu, H.K. and Deng, C. X. (2005) Identification and characterization of a novel adhesin unique to oral fusobacteria. J. Bacteriol. 187: 5330-5340.
Han, Y.W., Redline, R.W., Li, M., Yin, L., Hill, G.B. and McCormick, T.S. (2004) F. nucleatum induces premature and term stillbirths in pregnant mice: implication of oral bacteria in preterm birth. Infect. Immun. 72: 2272-2279.