Dr. Songlin Wang graduated with DDS and Ph.D. degrees in Oral Maxillofacial Surgery and Radiology (supervised by Prof. Zhaoju Zou) from Peking University Health Science Center in 1989. After working for a while at Capital Medical University, he became a visiting scholar at Tokyo Medical and Dental University in 1991 and a visiting scientist at the National Institutes of Health in Prof. Bruce Baum’s lab from 1996 to 1998 and then again in 2001.

He is an academician of the Chinese Academy of Sciences, Dean of School of Medicine, South University of Science and Technology (SUSTech), Vice President of the Chinese Stomatological Association, and the Beijing Medical Association. He is also the Chief Professor and Chairman of the Beijing Laboratory of Oral Health, Capital Medical University. He has been inducted as an ad hominem fellow of the Royal College of Surgeons of Edinburgh.

His main research interests are the regeneration and functional reconstruction of oral and maxillofacial defects and the diagnosis and treatment of salivary gland diseases. He has performed pioneering work on the discovery of Sialin (SLC17A5) as a nitrate transporter in the cell membrane and the biological functions of nitrate; restoration of salivary hypofunction; development of dental pulp stem cells as a new stem cell drug; regeneration of tooth and periodontal tissues; and discovery of the mammalian tooth replacement mechanism. These achievements have been included in many international academic monographs, textbooks, and invited reviews. He has authored more than 269 peer-reviewed articles in PNAS, EMBO J, Blood, and Nature Communications, among others, and 16 review articles. So far, he has edited 8 books and 12 book chapters.

Discovered Sialin (SLC17A5) as a nitrate transporter, Sialin2 as nitrate sensor, elucidated the molecular mechanism of high concentration nitrate in parotid glands, and discovered the novel important physiological and clinical functions of nitrate in the protection of gastrointestinal and other organs

A series of studies has been conducted to clarify the functional role of salivary glands in nitric oxide homeostasis. Dr. Wang discovered that the parotid gland was an important organ that mediated nitrate metabolism and dynamic balance through entero-salivary circulation (Xia et al., 2003). Then he focused on this physiological phenomenon and discovered the first mammalian nitrate transporter Sialin (SLC17A5) in the plasma membrane (Qin et al., 2012). Furthermore, he has discovered that Sialin2 is sensor of nitrate in the organelle membrane and nitrate-Sialin-Sialin2 mediates cell biological functions (Li et al., 2024). Based on these novel findings, he proposed a new concept of Homeostatic Medicine (Wang et al., 2022). As SLC17A5 would lead to embryonic lethality after ablation, Dr. Wang established a one-step method to generate viable chimeric founder mice, in which CRISPR reagents were injected into one blastomere of two-cell embryos, facilitating the study of the in vivo functions of the associated lethal genes (Wu et al., 2019). He found that stress promotes salivary nitrate secretion and nitrite formation, which play important roles in gastric protection against stress-induced injury via the nitrate-dependent NO pathway in humans and rats (Jin et al., 2013). Dietary nitrate can prevent and rescue senescence-related decline in liver function, alleviates irradiation-induced damage to salivary glands and whole body, rebalancing the glucolipid metabolism and gut microbiome dysbiosis in obesity and colitis, etc. induced by a high-fat diet (Wang et al., 2018; Hu et al., 2019; Chang et al., 2018; Ma et al., 2020; Wang et al., 2020; Li et al., 2021, Feng et al., 2021). Based on the publications above, Dr. Wang developed a new drug named Nitrator, the main component of nitrate and vitamin C (Pan et al., 2022). His recent data showed Nitrator has a widespread protection function and potential wide clinical applications.

Established the new classification and treatment guideline for chronic inflammatory parotid gland diseases

Salivary hypofunction is usually caused by acute/chronic inflammatory disease, Sjögren’s syndrome, or irradiation. It severely affects patients’ quality of life and used to be irreversible and without effective treatment. Dr. Wang aims to restore the salivary function through various approaches. He has established a new classification and treatment guideline for chronic inflammatory parotid gland diseases. Besides, he drafts the guidelines and promotes the clinical application of sialoendoscopy for the diagnosis and treatment of salivary gland diseases in China. He has found that bone marrow mesenchymal stem cells in human Sjögren’s syndrome patients have defects in terms of the immunoregulatory functions. Then his team successfully relieved the symptoms of patients with Sjögren’s syndrome by transplanting allogeneic mesenchymal stem cells that laid the foundation for uncovering its potential mechanisms (Xu et al., 2012; Hu et al., 2020). Besides, he has found that the early-stage damage to microvascular endothelial cells was an important pathogen of irradiation-induced salivary hyposalivation, and alleviated and prevented the irradiation-induced hyposalivation in a miniature pig model by transferring adenoviral-mediated human aquaporin-1 (AQP1), fibroblast growth factor-2 (FGF2), or sonic hedgehog (Shh) gene into the salivary gland, as well as systemic Rapamycin administration (Shan et al., 2005; Zhu et al., 2016; Hu et al., 2018)

Developed a human dental pulp stem cell drug, proposed and realized the concept of “bio-root regeneration”

Although dental implants are now widely applied in clinics, complications such as peri-implantitis and bone injury are still unresolved due to their non-physiological restoration. Currently, researchers are aiming to regenerate bioengineered teeth that have physiological structures and functions similar to those of natural teeth. Dr. Wang successfully regenerated a root/periodontal complex (Bio-root) capable of supporting a porcelain crown in a miniature pig by transplanting mesenchymal stem cells (Sonoyama et al., 2006; Wei et al., 2012). Bio-roots are similar to natural tooth roots in elemental composition, compressive strength, modulus of elasticity, and torsional force compared to dental implants (Gao et al., 2016). These superiorities could potentially allow bio-roots to replace the dental implants and be a better route for tooth restoration.

Periodontitis is among one of the most prevalent oral diseases in China, resulting in the destruction of tooth-supporting tissues and tooth loss. Existing periodontal treatments, including basic periodontal treatment and guided tissue regeneration, have limited effects and poor clinical predictability. Dr. Wang found the periodontal ligament stem cells (PDLSCs) in periodontitis had markedly dysfunctional immunomodulatory properties. He set up a periodontitis model in miniature pigs, then demonstrated that periodontal tissues could be regenerated by transplanting PDLSCs into the periodontal defects in the miniature pig model (Liu et al., 2008). Mechanically, he discovered that allogeneic PDLSCs mediated periodontal tissue regeneration through low immunogenicity, marked immunosuppression via PGE2-induced T-cell anergy, and suppressed B cell activation through PD1/PDL1 (Ding et al., 2010; Liu et al., 2013). Furthermore, he showed that both autologous and allogeneic dental pulp stem cells (DPSCs) could significantly regenerate periodontal tissues in both periodontitis miniature pigs and periodontitis patients after cell injection or cell sheet transplantation (Hu et al., 2016). He also found DPSCs engender enhanced tissue regeneration and have superior resistance to lipopolysaccharide-induced apoptosis and senescence (Ma et al., 2019). Based on these studies, he successfully developed a human dental pulp stem cell drug as a new treatment for periodontitis. Recently, Dr. Wang has obtained tacit approval from the Centre for Drug Evaluation, National Medical Products Administration and have performed investigator-initiated clinical trial (IIT) of 129 patients with chronic periodontitis and clinical trial phase-I of 37 cases with chronic periodontitis (Liu et al., 2024). Now the clinical trial phase II is underway.

Discovered a mammalian tooth replacement mechanism and realized whole tooth regeneration in miniature pigs

Distinct from rodents, miniature pigs have two sets of teeth, the deciduous and permanent teeth, which are similar to those of humans. This character makes the miniature pig a good model to explore molecular mechanisms of human teeth development and replacement. The ultimate goal is to elucidate the mechanism of permanent teeth loss and their ability to be replaced by third dentition and realize whole teeth regeneration in adult humans. Over the past decade, Dr. Wang has focused on the miniature pig model to reveal the mechanism of tooth development and replacement. His team has described the exact chronological stages of different teeth and established a multi-bioinformatics database through profiled stage-specific differential gene expression, DNA methylation, and microRNA expression during deciduous and permanent dentition morphogenesis (Wang et al., 2014; Song et al., 2014; Wang et al., 2014). Based on these novel findings, he has discovered that the mandible microenvironment was responsible for the initiation of tooth development. Notably, he has revealed that releasing the accumulated mechanical stress inside the mandible by deciduous tooth eruption can regulate permanent tooth development via the integrin β1-RUNX2-Wnt pathway (Wu et al., 2019). Furthermore, he established the bioengineered tooth bud by single cells’ reconstitution, addressed the efficient long-term survival and growth in vitro and in vivo, realized large size tooth regeneration when transplanted into mouse subrenal capsules or in miniature pig jawbone (Wang et al., 2018; Wu et al., 2019). Now he is focusing on development pattern and molecular mechanism of human tooth and jaw bones.

In 2007, Dr. Wang received the William J. Gies Award for Biological Research and Cover of the Year Award by AADR/IADR. In 2003 and 2010, as the first principal investigator, he received two National Science and Technology Advancement Awards of China (second class). He has been awarded the Wu Jieping Medical Innovation Award and the Ho Leung Ho Lee Foundation Medicine Pharmacy Prize. He has received funding from the National Key Basic Research Program of China (973), the National High Technology Research Program of China (863), and a key grant from the National Nature Science Foundation of China. He is associate editor of Oral Diseases, the Journal of Oral Rehabilitation, the Chinese Journal of Dental Research (in English), and the Chinese Journal of Stomatology. He is on the editorial board of several journals.

In addition, Dr. Songlin Wang has made great efforts to promote the development of China’s science and education. He served as President of the Chinese Society of Dental Education from 2007 to 2015. He chaired and enacted the educational and clinical practice guidelines of Stomatological Education in China, which is the cornerstone of the sustainable development and prosperity of national dental education. He founded the Society of Oral Biomedicine and the Chinese Stomatological Association (SOB-CSA), which is a prominent platform for training creative young Chinese talents and accommodating international academic communication in 2010, and the most prestigious dental society in China. He has supervised over 90 Ph.D. students, 29 postgraduate students, and 27 postdoctoral fellows.

References

1. Chang, S., Hu, L., Xu, Y., Li, X., Ma, L., Feng, X., Wang, J., Zhang, C., & Wang, S. (2019). Inorganic nitrate alleviates total body irradiation-induced systemic damage by decreasing reactive oxygen species levels. International journal of radiation oncology, biology, physics, 103(4), 945–957.

2. Ding, G., Liu, Y., Wang, W., Wei, F., Liu, D., Fan, Z., An, Y., Zhang, C., & Wang, S. (2010). Allogeneic periodontal ligament stem cell therapy for periodontitis in swine. Stem cells (Dayton, Ohio), 28(10), 1829–1838.

3. Feng, X., Wu, Z., Xu, J., …… Wang, S. (2021). Dietary nitrate supplementation prevents radiotherapy-induced xerostomia. eLife. 2021b. https:// doi. org/10. 7554/ eLife. 70710.

4. Feng, Y., Cao, X., Zhao, B., …… Hu, J.Q., Wang, S. (2021) Nitrate increases cisplatin chemosensitivity of oral squamous cell carcinoma via REDD1/AKT signaling pathway. Sci China Life Sci. https:// doi. org/ 10. 1007/s11427- 020- 1978-4.

5. Gao, Z. H., Hu, L., Liu, G. L., Wei, F. L., Liu, Y., Liu, Z. H., Fan, Z. P., Zhang, C. M., Wang, J. S., & Wang, S. L. (2016). Bio-root and implant-based restoration as a tooth replacement alternative. Journal of dental research, 95(6), 642–649.

6. Hu, J., Cao, Y., Xie, Y., Wang, H., Fan, Z., Wang, J., Zhang, C., Wang, J., Wu, C. T., & Wang, S. (2016). Periodontal regeneration in swine after cell injection and cell sheet transplantation of human dental pulp stem cells following good manufacturing practice. Stem cell research & therapy, 7(1), 130.

7. Hu, L., Jin, L., Xia, D., Zhang, Q., Ma, L., Zheng, H., Xu, T., Chang, S., Li, X., Xun, Z., Xu, Y., Zhang, C., Chen, F., & Wang, S. (2020). Nitrate ameliorates dextran sodium sulfate-induced colitis by regulating the homeostasis of the intestinal microbiota. Free radical biology & medicine, 152, 609–621.

8. Hu, L., Xu, J., Wu, T., Fan, Z., Sun, L., Liu, Y., Li, Y., Zhang, C., Wang, J., Ding, Y., & Wang, S. (2020). Depletion of ID3 enhances mesenchymal stem cells therapy by targeting BMP4 in Sjögren's syndrome. Cell death & disease, 11(3), 172.

9. Hu, L., Zhu, Z., Hai, B., Chang, S., Ma, L., Xu, Y., Li, X., Feng, X., Wu, X., Zhao, Q., Qin, L., Wang, J., Zhang, C., Liu, F., & Wang, S. (2018). Intragland Shh gene delivery mitigated irradiation-induced hyposalivation in a miniature pig model. Theranostics, 8(16), 4321–4331.

10. Jin, L., Qin, L., Xia, D., Liu, X., Fan, Z., Zhang, C., Gu, L., He, J., Ambudkar, I. S., Deng, D., & Wang, S. (2013). Active secretion and protective effect of salivary nitrate against stress in human volunteers and rats. Free radical biology & medicine, 57, 61–67.

11. Li, J., Shan, Z., Ou, G., Liu, X., Zhang, C., Baum, B. J., & Wang, S. (2005). Structural and functional characteristics of irradiation damage to parotid glands in the miniature pig. International journal of radiation oncology, biology, physics, 62(5), 1510–1516.

12. Li, S., Jin, H., Sun, G., Zhang, C., Wang, J., Xu, H., Zhang, D., & Wang, S. (2021). Dietary inorganic nitrate protects hepatic ischemia-reperfusion injury through NRF2-mediated antioxidative stress. Frontiers in pharmacology, 12, 634115.

13. Li, X.Y., …… Wang, S. (2024). Discovery of Sialin2 as the sensor of nitrate in the organelle membrane.

14. Liu, O., Xu, J., Ding, G., Liu, D., Fan, Z., Zhang, C., Chen, W., Ding, Y., Tang, Z., & Wang, S. (2013). Periodontal ligament stem cells regulate B lymphocyte function via programmed cell death protein 1. Stem cells (Dayton, Ohio), 31(7), 1371–1382.

15. Liu, Y., Hu J.T., Liu Y.T., …… Wu Z.Z., Wang, S. Clinical study and a phase I  clinical trial of allogeneic human dental pulp stem cells injection in the treatment of chronic periodontitis.

16. Liu, Y., Zheng, Y., Ding, G., Fang, D., Zhang, C., Bartold, P. M., Gronthos, S., Shi, S., & Wang, S. (2008). Periodontal ligament stem cell-mediated treatment for periodontitis in miniature swine. Stem cells (Dayton, Ohio), 26(4), 1065–1073.

17. Ma, L., Hu, L., Jin, L., Wang, J., Li, X., Wang, W., Chang, S., Zhang, C., Wang, J., & Wang, S. (2020). Rebalancing glucolipid metabolism and gut microbiome dysbiosis by nitrate-dependent alleviation of high-fat diet-induced obesity. BMJ open diabetes research & care, 8(1), e001255.

18. Ma, L., Hu, J., Cao, Y., Xie, Y., Wang, H., Fan, Z., Zhang, C., Wang, J., Wu, C. T., & Wang, S. (2019). Maintained properties of aged dental pulp stem cells for superior periodontal tissue regeneration. Aging and disease, 10(4), 793–806.p

19. Qin, L., Liu, X., Sun, Q., Fan, Z., Xia, D., Ding, G., Ong, H. L., Adams, D., Gahl, W. A., Zheng, C., Qi, S., Jin, L., Zhang, C., Gu, L., He, J., Deng, D., Ambudkar, I. S., & Wang, S. (2012). Sialin (SLC17A5) functions as a nitrate transporter in the plasma membrane. Proceedings of the National Academy of Sciences of the United States of America, 109(33), 13434–13439.

20. Pan,W., Hu, G., Li, S.R., …… Wang, X.G., Wang, Y.J., Wang, S. (2023). Nanonitrator: novel enhancer of inorganic nitrate’s protective effects, predicated on swarm learning approach. Science Bulletin,, 68: 838–850.

21. Shan, Z., Li, J., Zheng, C., Liu, X., Fan, Z., Zhang, C., Goldsmith, C. M., Wellner, R. B., Baum, B. J., & Wang, S. (2005). Increased fluid secretion after adenoviral-mediated transfer of the human aquaporin-1 cDNA to irradiated miniature pig parotid glands. Molecular therapy : the journal of the American Society of Gene Therapy, 11(3), 444–451.

22. Song, T., Wu, T., Wei, F., Li, A., Wang, F., Xie, Y., Liu, D., Fan, Z., Wang, X., Cheng, S., Zhang, C., He, J., & Wang, S. (2014). Construction of a cDNA library for miniature pig mandibular deciduous molars. BMC developmental biology, 14, 16.

23. Sonoyama, W., Liu, Y., Fang, D., Yamaza, T., Seo, B. M., Zhang, C., Liu, H., Gronthos, S., Wang, C. Y., Wang, S., & Shi, S. (2006). Mesenchymal stem cell-mediated functional tooth regeneration in swine. PloS one, 1(1), e79.

24. Wang, F., Wu, Z., Fan, Z., Wu, T., Wang, J., Zhang, C., & Wang, S. (2018). The cell re-association-based whole-tooth regeneration strategies in large animal, Sus scrofa. Cell proliferation, 51(4), e12479.

25. Wang, F., Xiao, J., Cong, W., Li, A., Song, T., Wei, F., Xu, J., Zhang, C., Fan, Z., & Wang, S. (2014). Morphology and chronology of diphyodont dentition in miniature pigs, Sus Scrofa. Oral diseases, 20(4), 367–379.

26. Wang, F., Xiao, J., Cong, W., Li, A., Wei, F., Xu, J., Zhang, C., Fan, Z., He, J., & Wang, S. (2014). Stage-specific differential gene expression profiling and functional network analysis during morphogenesis of diphyodont dentition in miniature pigs, Sus Scrofa. BMC genomics, 15, 103.

27. Wang, H., Hu, L., Li, L., Wu, X., Fan, Z., Zhang, C., Wang, J., Jia, J., & Wang, S. (2018). Inorganic nitrate alleviates the senescence-related decline in liver function. Science China Life Sciences, 61(1), 24–34.

28. Wang, S., Qin, L.Z. (2022) Homeostatic medicine: a strategy for exploring health and disease. Current Medicine, 1:16 (https://doi.org/10.1007/s44194-022-00016-9).

29. Wang, W., Hu, L., Chang, S., Ma, L., Li, X., Yang, Z., Du, C., Qu, X., Zhang, C., & Wang, S. (2020). Total body irradiation-induced colon damage is prevented by nitrate-mediated suppression of oxidative stress and homeostasis of the gut microbiome. Nitric oxide : biology and chemistry, 102, 1–11.

30. Wei, F., Song, T., Ding, G., Xu, J., Liu, Y., Liu, D., Fan, Z., Zhang, C., Shi, S., & Wang, S. (2013). Functional tooth restoration by allogeneic mesenchymal stem cell-based bio-root regeneration in swine. Stem cells and development, 22(12), 1752–1762.

31. Wu, X., Hu, J., Li, G., Li, Y., Li, Y., Zhang, J., Wang, F., Li, A., Hu, L., Fan, Z., Lü, S., Ding, G., Zhang, C., Wang, J., Long, M., & Wang, S. (2020). Biomechanical stress regulates mammalian tooth replacement via the integrin β1-RUNX2-Wnt pathway. The EMBO journal, 39(3), e102374.

32. Wu, Y., Zhang, J., Peng, B., Tian, D., Zhang, D., Li, Y., Feng, X., Liu, J., Li, J., Zhang, T., Liu, X., Lu, J., Chen, B., & Wang, S. (2019). Generating viable mice with heritable embryonically lethal mutations using the CRISPR-Cas9 system in two-cell embryos. Nature communications, 10(1), 2883.

33. Wu, Z., Wang, F., Fan, Z., Wu, T., He, J., Wang, J., Zhang, C., & Wang, S. (2019). Whole-tooth regeneration by allogeneic cell reassociation in pig jawbone. Tissue engineering. Part A, 25(17-18), 1202–1212.

34. Xia, D. S., Deng, D. J., & Wang, S. L. (2003). Destruction of parotid glands affects nitrate and nitrite metabolism. Journal of dental research, 82(2), 101–105.

35. Xu, J., Wang, D., Liu, D., Fan, Z., Zhang, H., Liu, O., Ding, G., Gao, R., Zhang, C., Ding, Y., Bromberg, J. S., Chen, W., Sun, L., & Wang, S. (2012). Allogeneic mesenchymal stem cell treatment alleviates experimental and clinical Sjögren syndrome. Blood, 120(15), 3142–3151.

36. Zhu, Z., Pang, B., Iglesias-Bartolome, R., Wu, X., Hu, L., Zhang, C., Wang, J., Gutkind, J. S., & Wang, S. (2016). Prevention of irradiation-induced salivary hypofunction by rapamycin in swine parotid glands. Oncotarget, 7(15), 20271–20281.