Huizhi Wang, PhD

Huizhi Wang, PhD

Huizhi Wang, PhD

Huizhi Wang, Ph.D.; M.D.
Assistant Professor, 
Department of Oral Immunology and Infectious Diseases,
Room 263D, School of Dentistry, 
Phone: (502) 852 1583

Research Interests:

Oral bacterial-induced host immune responses are critical to the initiation and progression of both periodontal diseases and some systemic diseases including atherosclerosis, diabetes, arthritis, and cancers. Such responses can be protective, and control the bacteria challenge, or destructive through prolonged or excessive production of endogenous mediators of inflammation and tissue remodeling.

Our studies mainly focus on the signaling pathways that regulate the nature and magnitude of the host inflammatory immune response as well as the identification of the potential targets for intervention.  Inhibition or interference with these pathways is a potential avenue to ameliorate the severity of inflammatory diseases and aid in the development of novel and innovative immunotherapeutics.  We are particularly interested in (1) how do oral pathogens, such as P. gingivalis, activate the anti-inflammatory signaling pathways and, thus, modify inflammation responses; and (2) how does host innate immune system respond to the bacterial infection and maintain immune homeostasis?   Currently, we are investigating the regulatory roles of serine/threonine protein kinases and HECT E3 ubiquitin ligase, especially related to the phosphoinositide 3-kinase (PI3K), such as Janus kinases (JAKs), glycogen synthase kinase-3 (GSK3), serum glucocorticoid-induced kinase-1 (SGK1), forkhead box O1 (FoxO1) and Nedd4L, in P. gingivalis-mediated inflammatory immune responses. We are also assessing the feasibility of these signaling molecules as potential anti-inflammatory therapeutic targets in vivo.

The other lab focus is to define the association between the infection of oral pathogens and the progression of esophageal squamous cell carcinoma (ESCC), and elucidate the underlying molecular mechanisms.  Our preliminary study has demonstrated the infection of P. gingivalis in esophagus epithelium promotes the progression and aggravates the prognosis of ESCC. Thus, our attention is currently focused on (i) the effects of P. gingivalis infection on the proliferation, apoptosis, invasion, and migration of cancer cells; (ii) the possible causal relationship between P. gingivalis infection and initiation of ESCC; and (iii) the molecular mechanisms that P. gingivalis infection exploited to subvert the host cell machinery for its pro-tumorigenic property.  

Current Funding:

SGK1 and the control of periodontal inflammation (NIH/NIDCR R01 DE026727)

Selected Publications

  1. Gao S., Li S., Duan X., Gu Z., Ma Z., Yuan X., Feng X., Wang H*. Inhibition of glycogen synthase 3 beta (GSK3b) suppresses the progression of esophageal squamous cell carcinoma by modifying STAT3 activity. Mol Carcinog, 2017, Oct; 56 (10): 2301-2316.
  2. Yuan X., Liu Y., Kong J., Gu B., Qi Y., Wang X., Sun M., Chen P., Sun W., Wang H., Zhou F., Gao S. Different frequencies of Poryphyromonas gingivalis infection in cancers of the upper digestive tract. Cancer Lett. 2017 Sep; 404:1-7.
  3. Kuboniwa M, Houser JR, Hendrickson EL, Wang Q, Alghamdi SA, Sakanaka A, Miller DP, Hutcherson JA, Wang H, Marcotte EM, Lamont RJ. Metabolic crosstalk regulates Porphyromonas gingivalis colonization and virulence during oral polymicrobial infection. Nat Microbial, 2017 Sep 18. doi: 10.1038/s41564-017-0021-6
  4. Wang D., Gao S., Kong G., Li S., Wang W., Wang H*., Zhou F. Expression of Serum- and Glucocorticoid- regulated kinase 1(SGK1) and its association with the clinicopathological factor and survival of the patients with adenocarcinoma in esophagogastric Junction. Oncology Letter,2017 May; 13(5):3572-3578.
  5. Sztukowska M.N., Ojo A., Ahmed S., Carenbauer A.L., Wang Q., Shumway B., Jenkinson H.F., Wang H., Darling D.S., Lamont R.J. Porphyromonas gingivalis initiates a mesenchymal-like transition through ZEB1 in gingival epithelial cells Cell Microbiol. 2016 Jun;18(6):844-58. PMID: 26639759.
  6. Yin H, Zhou H, Kang Y, Zhang X, Duan X, Alnabhan R, Liang S, Scott DA, Lamont RJ, Shang J, Wang H*. Syk negatively regulates TLR4-mediated IFNb and IL-10 production and promotes inflammatory response in dendritic cells. Biochim Biophys Acta. 2016 Mar; 1860(3):588-98.
  7. Zhou H, Gao S, Duan X, Liang S, Scott DA, Lamont RJ, Wang H*.  Inhibition of Serum- and Glucocorticoid- inducible kinase 1 (SGK1) Enhances TLR-mediated Inflammation and Promotes Sepsis-driven Organ Failure. FASEB J, 2015 Sep; 29(9):3737-49.
  8. Gao S, Li S, Ma Z, Liang S, Shan T, Zhang M, Zhu X, Zhang P, Liu G, Zhou F, Yuan X, Jia R, Potempa J, Scott DA, Lamont RJ, Wang H*, Feng X*.  Presence of Porphyromonas gingivalis in Esophagus and Its Association with the Clinicopathological Characteristics and Survival in Patients with Esophageal Squamous Cell Carcinoma; Infectious Agents and Cancer 2016 Jan 19;11:3
  9. Wang Q, Sztukowska M, Ojo A, Scott DA, Wang H, Lamont RJ. FOXO responses to Porphyromonas gingivalis in epithelial cells. Cell Microbiol. 2015 Nov;17(11):1605-17.
  10. Wang H., Lamont RJ., Scott DA.  Glycogen Synthase Kinase 3-b and the Control of Infectious Bacterial Diseases. Trends in Microbiology, 2014 22:208-217.
  11. Wang H*., Zhou H., Jotwani R., ScottDA., Lamont RJ*. Porphyromonas gingivalis-Induced Reactive Oxygen Species (ROS) Activates JAK2 and Regulates the Production of Inflammatory Cytokines Through Multiple Signaling Pathways. Infection and Immunity, 2014 82:4118-4126.
  12. Wang H*., Brown J., Gao S., Liang S., Zhou H., Jotwani, R. Suttles J., Scott DA., Lamont RJ*. The role of Janus Kinase (JAK)-3 in Regulating Toll-Like Receptor-Mediated Inflammatory Cytokine Production in Innate Immune Cells.  Journal of Immunology, 2013 191:1164-74.
  13. Wang H*., Brown J., Suttles J*., Graves DT, Martin M. mTORC2 Negatively Regulates the Toll-like Receptor 4 Mediated Inflammatory Response Via FoxO1. Journal of Biology and Chemistry, 2011 286: 44295-44305.
  14. Wang H*, Brown J, Garcia C, Liang R, Alard, P, Beurel E, Jope R, Greenway T, Martin M. Convergence of the Mammalian Target of Rapamycin Complex 1- and Glycogen Synthase Kinase 3- Signaling Pathways Regulates the Innate Inflammatory Response.  Journal of Immunology, 2011 186: 5217-5226.
  15. Wang H, Brown J, Hajishengallis G, Martin M. TLR-signaling Networks:  An Integration of Adaptor Molecules, Kinases, and Crosstalk.  Journal of Dental Research, 2011 90: 417-427.
  16. Wang H, Benakanakere, M.R., Garcia CA, Kinane DF, Martin M. The Role of Glycogen Synthase Kinase 3-beta (GSK3-beta) In the Interferon-beta (IFN-beta)-mediated IL-10 production. Journal of Immunology, 2011 186: 675-684.
  17. Wang H, Garcia CA, Rehani K, Cekic C, Alard P, Kinane DF, Alard P, Mitchell T, Martin M. IFN-beta production by TLR4-stimulated innate immune cells is negatively regulated by GSK3-beta. Journal of Immunology, 2008 181: 6797-6802.
  18. Wang H, Rehani K, Garcia CA, Kinane DF, Martin M. Toll-like receptor-mediated production of IL-1Ra is negatively regulated by GSK3 via the MAPK ERK1/2, Journal of Immunology, 2009 182: 547-553.