The COR Team is a network of colleagues from UCSF, international affiliates, students, and corporate partners.
Dr. Pamela DenBesten is a pediatric dentist, with a focus on the translation of pediatric dental research to clinical care for children. Dr DenBesten completed her dental training and obtained a DDS degree from the University of Iowa. She then completed a MS and residency in pediatric dentistry at the University of North Carolina at Chapel Hill, followed by additional postdoctoral training at the Forsyth Dental Center, Boston, MA.
The focus of research in the DenBesten laboratory is related to tooth formation, including the mechanism of dental fluorosis. Her research interests also include the use of stem cells in tooth regeneration, and how enamel maturation results in optimal enamel biomineralization. Of particular interest to her are the causes and treatment of amelogenesis imperfecta.
DenBesten is the Professor and co-director of the UCSF DDS/PhD and PhD programs in Oral and Craniofacial Sciences, and the Director for COR.
DenBesten is a member of the International and American Associations for Dental Research, the American Association for the Advancement of Science (AAAS), the American Academy of Pediatric Dentistry, California Society of Pediatric Dentistry, and is a diplomat of the American Board of Pediatric Dentistry. She was a member of the NIDCR Board of Counselors from 2011-2015, was named a Fellow of the AAAS in 2012, and received a Distinguished Scientist Award from the International Association for Dental Research in 2009.
St. Olaf College at Northfield Minn. 1976, BS Chemistry
University of Iowa at Iowa City 1980, DDS
University of North Carolina at Chapel-Hill (UNC) 1983, Certificate in Pediatric Dentistry
UNC 1983, MS in Pediatric Dentistry
UNC 1983-1985, Post-doctoral Fellow in Pediatric Dentistry and Biomineralization
Boyce WT, Den Besten PK, Stamperdahl J, Zhan L, Jiang Y, Adler NE, Featherstone JD.
Social inequalities in childhood dental caries: the convergent roles of stress, bacteria and disadvantage.
Soc Sci Med. 2010 Nov; 71(9):1644-52.
Lyaruu DM, Medina JF, Sarvide S, Bervoets TJ, Everts V, DenBesten P, Smith CE, Bronckers AL (2014) Barrier formation: Potential molecular mechanism of enamel fluorosis.
J Dent Res 93:96-102.
Zhang Y, Kim JY, Horst O, Nakano Y, Zhu L, Radlanski RJ, Ho S, Den Besten PK.
Fluorosed Mouse Ameloblasts Have Increased SATB1 Retention and Gaq Activity.
PLoS One. 2014; 9(8):e103994. PMID: 25090413. PMCID: PMC4121220
Katsura KA, Horst JA, Chandra D, Le TQ, Nakano Y, Zhang Y, Horst OV, Zhu L, Le MH, DenBesten PK (2014) WDR72 models of structure and function: A stage-specific regulator of enamel mineralization. Matrix Biology 38:48-58.
Dr. Thuan Le is a scientist and pediatric dentist, who cares for children and adolescents in both the UCSF Benioff Children's Hospital Pediatric Dentistry Out-patient Clinic and in the operating room setting. He serves healthy children as well as those with complex medical conditions.
In addition to teaching and caring for patients, Dr Le conducts research on tooth development and inherited tooth defects. His research interest is to investigate the structures and functions of enamel extracellular matrix proteins in tooth formation, with particular emphasis on alternatively spliced amelogenins. Mutations in these enamel matrix proteins result in inherited enamel defects, called amelogenesis imperfect. He also is interested in investigate the outcome assessments of pediatric dentistry performed under conscious sedation.
Le completed his undergraduate B.S. degree (Chemistry) and dental training at the University of North Carolina at Chapel Hill, N.C., before coming to UCSF to obtain a certificate in pediatric dentistry and a Ph.D. in Oral and Craniofacial sciences.
Le is an associate professor of clinical orofacial sciences at UCSF, and director of the postgraduate pediatric dentistry residency program. He was awarded the 2013 Academic Senate Distinction in Teaching Award for faculty at UCSF five years or fewer, and was also a recipient of Eric B. Bystrom Pediatric Dentistry Memorial Award, for excellence in caring for special-need pediatric patients from UCSF Pediatric Dentistry, 2002.
Le is a member of the American Academy of Pediatric Dentistry and the California Society of Pediatric Dentistry, and is a diplomate of the American Board of Pediatric Dentistry.
Education
University of North Carolina at Chapel Hill 1995, BS Chemistry
University of North Carolina at Chapel Hill 1999, DDS (Dentistry)
University of California San Francisco 2002, Certificate in Pediatric Dentistry
University of California San Francisco 2007, PhD in Oral and Craniofacial Sciences.
Current research interest
1. A Retrospective Study of Chloral Hydrate Versus Midazolam Containing Triple-Cocktail Oral Sedation in Pediatric Dentistry.
The aim of the study is to evaluate retrospectively the safety and efficacy of two moderate oral conscious sedation drug regimens used at UCSF Pediatric Dentistry Clinic: chloral hydrate, meperidine, and hydroxyzine (CH/M/H) versus midazolam, meperidine, and hydroxyzine (Mid/M/H). The results concluded that the chloral hydrate regimen can be safely and effectively used in pediatric dental oral conscious sedation.
2. Pilot Study: Effect of Livionex on Plaque Accumulation and Oral Health in Children
The aim of this clinical trial study is to investigate the effectiveness of a commercially available Livionex toothpaste in reducing dental plaque accummulation and caries, improving gingival health and thus over all oral health for children. Livionex uses a proprietary formulation of the calcium chelator, EDTA, to break up the dental plaque biofilm. EDTA is deposited onto the tooth surface while brushing, which increases the negative charge on the tooth surface. This prevents the adhesion and accumulation of negatively charged biofilm, reducing caries and improving gingival health.
3. Functional Remineralization of Dentin Lesions Using PILP-releasing glass ionomer cement.
(In collaboration with Stefan Habelitz to mentor a summer research student’s project, Hoorsad Fathi-Kelly).
The goal of this research is to demonstrate osteopontin (OPN) enhances the functionality of glass-ionomer cement (GIC) formulations used in dental applications to achieve functional remineralization of dentin tissue. We hypothesize that these OPN-GICs will provide the chemical environment necessary to activate the polymer-induced liquid-precursor (PILP) process required to introduce apatite mineral into collagen fibrils (intrafibrillar mineral). The aims are to determine if
A successful demonstration will facilitate transitioning functional remineralization of dentin lesions in the laboratory to an applicable restorative dental treatment in the clinic.
4. Remineralization Potentials of Polyaspartic-acid Modified Glassionomer in Demineralized Dentin Matrix.
- The purpose of this study is to compare the ability of resin-modified glassionomer Biocem cement (NuSmile, Houston, TX) and Biocem cement modified with polyaspartic acid (Biocem+Polyaspartic acid) in their ability to remineralize and restore the mechanical properties of demineralized dentin matrix in artificial lesions in extracted human molars.
Selected Research and Publications
Le TQ, Zhang Y, Li W, Denbesten PK. The effect of LRAP on enamel organ epithelial cell differentiation. J Dent Res. 2007 Nov; 86(11):1095-9.
Le TQ, Gochin M, Featherstone JD, Li W, DenBesten PK. Comparative calcium binding of leucine-rich amelogenin peptide and full-length amelogenin. Eur J Oral Sci. 2006 May; 114 Suppl 1:320-6; discussion 327-9, 382.
Ye L, Le TQ, Zhu L, Butcher K, Schneider RA, Li W, DenBesten PK (2006). Amelogenins in human developing and mature dental pulp. J Dent Res 85(9):814-8.
Tanimoto K, Le TQ, Zhu L, Chen JL, Featherstone JDB, Li W, DenBesten PK (2008). Effects of fluoride on the interactions between amelogenin and apatite crystal. J. Dent Res 87(1):39-44.
Tanimoto K, Le TQ, Zhu L, Witkowska HE, Robinson S, Hall S, Hwang P, DenBesten PK, Li W (2008). Reduced amelogenin-MMP20 interactions in amelogenesis imperfecta. J Dent Res 87(5):451-455
Dr. Wu Li, is a biochemist researcher working on the tooth enamel biomineralization, focusing on the roles of matrix proteins and proteinases in the development of tooth enamel and dental diseases.
Dr Li's research project involves the investigation of the functions of amelogenins, including their structure-function relationship with enamel matrix proteinases and apatite crystals, as well as their roles as signaling molecules in tooth enamel development. His research aims to determine how the amelogenin self-assembly affects their disassembly and degradation of amelogenin by proteinases. His work also includes studies of the mechanism of enamel and dentin diseases including dental fluorosis, amelogenesis imperfecta, pulp defects and dental caries. His research has been supported by NIH/NIDCR fundings. He is using biochemical and biophysical approaches to study enamel matrix proteins, enamel and dentin proteinases and their interactions and study how the gene mutations results in the changes of protein functions and protein-protein interactions in diseases and development.
Li graduated with a MD degree from Three Gorges University School of Medicine, and a PhD degree from Tongji Medical University in China. He finished his postdoctoral researcher training at the University of Rochester, NY and UCSF, San Francisco.
Li is a member of the International and American Associations for Dental Research.
University of Rochester, 1994-1995, Postdoctoral fellow in Biochemistry and Biomineralization.
University of California at San Francisco, 1995-1999, Postdoctoral fellow in Biochemistry and Biomineralization.
Huang Y, Goldberg M, Zhu L, Le T, Qiang R, Liu H, Witkowska HE, DenBesten P, Li W. Effects of Amelogenin Exons 8 and 9 on Postnatal DPCs. Cell Tissues Organs Cells Tissues Organs. 2012 Feb 1. PMCID: PMC3677967
Zhu L, Uskokovic V, Liu H, Tanimoto K, Witkowsk HE, Li W. Removal of amelogenin from hydroxyapatite crystals by MMP20 and KLK4. Frontier in Physiology, 2014, 5:1-8.
Zhu L, Uskoković V, Le T, Tanimoto K, DenBesten P, Huang YL, Habelitz S, Li W. Altered self-assembly and apatite binding of amelogenin induced by N-terminal proline mutation. Arch Oral Biol. 2011 Apr;56(4):331-6.
Tanimoto K, Le T, Zhu L, Chen J, Featherstone JD, Li W, DenBesten P. Effects of fluoride on the interactions between amelogenin and apatite crystals. J Dent Res. 2008 Jan;87(1):39-44. PMCID: PMC3435094
Dr. Yukiko Nakano is a dentist scientist studying the basic science of tooth and bone biology with particular focus on the field of children’s oral health.
Dr. Nakano’s research interests are the mechanisms that direct the development of bio-mineralized tissues. During tooth and bone formation, differentiation and activity of participant cells are systematically regulated by extracellular and intracellular signals, allowing cells to deposit the extracellular matrix (ECM) proteins. Particularly, she is interested in the mechanisms of how the cells that form bone and tooth, modulate matrix production, and the role of phosphatases in matrix biomineralization.
She is also interested in how to successfully integrate dental implants, orchestrate tooth movement during orthodontic treatment, and recover functionality of teeth and bone after oral surgery, which all require well-controlled bone modeling, augmentation and/or regeneration. Nakano’s research is elucidating the understanding of certain fundamental aspects of how bone volume, shape, density and its mineralization are regulated.
Unlike other mineralized tissues, in tooth enamel formation, extracellular matrix deposition and mineralization occurs in unique and sequential steps giving a great advantage in easier examining cellular activity regulating biomineralization. To understand the mechanisms how the enamel forming cells (ameloblasts) switch their function and thus execute the tooth enamel matrix formation and mineralization, Nakano’s research projects are currently focusing on three steps of ameloblast differentiation. 1) How ameloblast precursors (stem cell) becomes a pre-secretory ameloblast; 2) How pre-secretory ameloblasts differentiate in to a matrix secreting cells; 3) How maturation ameloblasts regulates enamel matrix mineralization.
Nakano received both a DDS and a Ph.D. degree from the Tokyo Medical and Dental University (TMDU). Following her training and research as a trainee and later as an assistant professor at TMDU, she completed her postdoctoral fellowship at McGill University, Montreal, Canada. Currently she is a Research Assistant Professor at UCSF.
Dr. Nakano is a member of the steering committee at COR.
Tokyo Medical and Dental University 2000, DDS
Graduate School of Tokyo Medical and Dental University 2005, PhD in Dental Science
McGill University 2005-2009, Postdoctoral Fellow in Dentistry and Biomineralization
Nakano Y, Beertsen W, VanDenbos T, Kawamoto T, Oda K, Takano Y 2004 Site-specific localization of two distinct phosphatases along the osteoblast plasma membrane: tissue non-specific alkaline phosphatase and plasma membrane calcium ATPase. Bone 35(5):1077-1085.
Nakano Y, Toyosawa S, Takano Y 2004 Eccentric localization of osteocytes expressing enzymatic activities, protein, and mRNA signals for type 5 tartrate-resistant acid phosphatase (TRAP). J Histochem Cytochemi 52(11):1475-1482.
Nakano Y, Addison WN, Kaartinen MT 2007 ATP-mediated mineralization of MC3T3-E1 osteoblast cultures. Bone 41(4):549-61.
Nakano Y, Forsprecher J and Kaartinen MT 2010 Regulation of ATPase activity of transglutaminase 2 by MT1-MMP: Implications for mineralization of MC3T3-E1 osteoblast cultures. J Cell Physiol 223(1):260-9.
Stahl J, Nakano Y, Horst J, Zhu L, Zhang Z, Liu H, Li W, DenBesten PK, 2015 Exon4 Transcribed Amelogenins Influence Enamel Biomineralization. J Dental Res (In Press)
Dr Rungnapa Yang is a pediatric dentist and a clinical researcher. Her research focuses on translational research study and the function of micro RNA during early enamel development. Her research has been honored and awarded from many organizations including the Nusmile Research Award from the American Academy of Pediatric Dentistry, the UCSF Research and Clinical Excellence Day, the University of Southern California Stevens Institute of Innovation as well as the University of Southern California School of Dentistry.
In addition to her research focus, Dr Yang also focuses her practice on clinical pediatric dental care as well as disease prevention at both UCSF Pediatric Dental Center and UCSF Benioff Children’s Hospital. She holds UCSF Medical Center Hospital Privilege and is a recipient of 2012 UCSF Pediatric Dentistry Excellence in Dental Care of Pediatric Disabled Patient Award.
She is a current member of the International and American Associations for Dental Research, the American Association for the Advancement of Science, the International Society for Stem Cell Research, the American Academy of Pediatric Dentistry, and the College of Diplomates of the American Board of Pediatric Dentistry.
Dr. Yang is currently a Health Science Assistant Clinical Professor and Assistant Researcher. She is also a board member for the UCSF Pediatric Alumni Board of Directors, serving as the Social Media Director.
Dr Yang received her dental degree from Chulalongkorn University in Thailand, her externship at the Tokyo Medical and Dental University and Keio University in Japan, her Pediatric Dentistry training from University of California, San Francisco, and her PhD from University of Southern California.
Chulalongkorn University 2000, DDS
University of Southern California 2008, PhD
University of California San Francisco 2012, Certificate in Pediatric Dentistry
Warotayanont R, Zhu D, Snead ML, Zhou Y. Leucine-rich amelogenin peptide induces osteogenesis in mouse embryonic stem cells. Biochem Biophys Res Commun. 2008 Feb 29;367(1):1-6.
Warotayanont R, Frenkel B, Snead ML, Zhou Y. Leucine-rich amelogenin peptide induces osteogenesis by activation of the Wnt pathway. Biochem Biophys Res Commun. 2009 Sep 25;387(3):558-63.
Yan Zhou, Christina.J. Newcomb, Rungnapa Warotayanont, Malcolm L. Snead, and S.I. Stupp. E-book title: Frontiers between Science and Clinic in Odontology. Volume 1: Amelogenins: Multifaceted Proteins for Dental and Bone Formation and Repair. Ch 16: Signaling Effect of Leucine-rich Amelogenin Peptide (LRAP) on Bone Regeneration. Bentham Science Publishers. 2010. 208-13.
Zheng L, Warotayanont R, Stahl J, Kunimatsu R, Klein O, Denbesten PK, Zhang Y. Inductive ability of human developing and differentiated dental mesenchyme. Cells Tissues Organs. 2013;198(2):99-110.
Le MH, Warotayanont R, Stahl J, Den Besten PK, Nakano Y. Amelogenin Exon4 Forms a Novel miRNA That Directs Ameloblast and Osteoblast Differentiation. J Den Res. 2015 Dec 29.
Dr. Zhan is a researcher and a pediatric dentist. She is interested in the microbiological aspects and translational research related to prevention of tooth decay in children, aiming to establish an individualized oral health care model for children, or precision pediatric dentistry. Her major research focus is to identify the virulent gene(s) in cavity-causing bacteria related to their transmission to children and initiation of tooth decay, using high-through-put genomic and meta-genomic assays to precisely identify and monitor children with high-virulent bacterial infection and targeted treatment regimens for children.
Dr Zhan's research interests include caries management by risk assessment protocols (CAMBRA), and development of regimens and guidelines for effective clinical practice. She is also interested in developing multi-disciplinary oral health programs in underdeveloped countries using the existing medical vaccination programs, the feasibility and efficacy of incorporating oral health education and fluoride varnish program through pediatric immunization clinics.
Zhan completed her dental training and PhD at the West China University of Medical Sciences. She obtained her pediatric dental residency program at UCSF Pediatric Dentistry.
Dr. Zhan is associate professor of clinical Orofacial Sciences, in Division of Pediatric Dentistry. She is a member of the International and American Associations for Dental Research, the American Academy of Pediatric Dentistry, and is a diplomate of the American Board of Pediatric Dentistry. She is the receipient of the Eric B. Bystrom Pediatric Dentistry Memorial Award, Division of UCSF Pediatric Dentistry.
College of Stomatology, West China University of Medical Sciences 1986-1992, DDS
College of Stomatology, West China University of Medical Sciences 1992-1997 , PhD
UCSF 2000-2003 Lee Hysan Scholar, visiting professor
UCSF 2003-2005 Postdoctoral fellow in Cariology
UCSF 2005-2008 Certificate in Pediatric Dentistry
Golinveaux J, Gerbert B, Cheng J, Duderstadt K, Alkon A, Mullen S, Lin B, Miller A, Zhan L. Oral health education for pediatric nurse practitioner students. J Dent Educ. 2013 May; 77(5):581-90.
Horst JA, Pieper U, Sali A, Zhan L, Chopra G, Samudrala R, Featherstone JD. Strategic protein target analysis for developing drugs to stop dental caries. Adv Dent Res. 2012 Sep; 24(2):86-93.
Zhan L, Featherstone JD, Lo J, Krupansky C, Hoang N, DenBesten P, Huynh T. Clinical efficacy and effects of xylitol wipes on bacterial virulence. Adv Dent Res. 2012 Sep; 24(2):117-22.
Zhan L, Cheng J, Chang P, Ngo M, Denbesten PK, Hoover CI, Featherstone JD. Effects of xylitol wipes on cariogenic bacteria and caries in young children. J Dent Res. 2012 Jul; 91(7 Suppl):85S-90S.
Zhan L, Tan S, Den Besten P, Featherstone JD, Hoover CI. Factors related to maternal transmission of mutans streptococci in high-risk children-pilot study. Pediatr Dent. 2012 Jul-Aug; 34(4):e86-91.
Dr. Yan Zhang is a cell biologist, whose research interests focus on ameloblast differentiation, and the roles of transcriptional regulator, specially AT-rich sequence-binding protein-1 (SABT1) in context of fluoride regulation.
More specifically, she is interested in the following questions:
What are the key signaling pathways from the dental mesenchyme, and intrinsic ameloblastic transcription factor networks that regulate ameloblast cell fate and differentiation?
How does fluoride affect the differentiation of ameloblasts and hippocampal dentate hilar cells to influence the amelogenesis and behavior of the rodents through altering the retention of chromosome organizer SATB1?
What are the biomarkers for the expansive and aggressive tumors of the jaw, known as ameloblastoma? The current surgical treatment causes disfiguring surgical removal of the mandibular (jaw) bone. By identifying biomarkers for ameloblastoma, new treatment approaches can be developed to specifically target ameloblastoma cells and reduce the need for surgical jaw resections.
Zhang is a member of the international and American Associations for Dental Research.
Zhang completed her PhD training in the Department of Pathology at Tongji Medical University in China. She received postdoctoral training at the Burnham Institute and the University of California at San Francisco.
Zhang Y, Lu H, Dazin P, Kapila YL. Squamous cell carcinoma cell aggregates escape suspension-induced, p53-mediated anoikis: fibronectin and integrin alphav mediate survival signals through focal adhesion kinase. Journal of Biological Chemistry. 2004, 279(46): 48342-48349.
Zhang Y, Yan QM, Li W, DenBesten PK. Fluoride down-regulates the expression of matrix metalloproteinase 20 in human fetal tooth ameloblast-lineage cells in vitro. European Journal of Oral Science. 2006 May; 114Suppl 1:105-110.
Zhang Y, Li W, Chi HS, Chen J, DenBesten PK. JNK/c-Jun signaling pathway mediates the fluoride-induced down-regulation of MMP-20 in vitro. Matrix Biology, 2007 Oct;26(8):633-41.
Zheng LW, Warotayanont R, Stahl J, Kunimatsu R, Klein O, Denbesten PK, Zhang Y. Inductive ability of human developing and differentiated Dental Mesenchyme. Cells Tissues Organs. 2013;198: 99-110
Zhang Y, Kim JY, Horst O, Nakano Y, Zhu L, Radlanski RJ, Ho S, Besten PK. Fluorosed Mouse Ameloblasts have increased SATB1 retention and Gαq activity. PLoS One. 2014 Aug 4; 9(8): 1-12