Oral & Craniofacial Sciences Graduate Group Faculty
Tamara Alliston Ph.D.
One in three American adults suffers from arthritis symptoms, yet the molecular basis of this degenerative skeletal disease remains unclear. Our research focuses on the molecular pathways controlling mesenchymal stem cell differentiation, how these pathways function in normal skeletal tissue, and how they can be harnessed to repair tissue damaged in degenerative skeletal disease. To answer these questions, we combine molecular, cellular, physiological, and materials science approaches. I believe this interdisciplinary strategy will lead to the identification of targets to prevent skeletal disease or to improve skeletal repair.
A current focus is to understand the mechanisms by which TGF-beta regulates osteoblast and chondrocyte differentiation. Cell-based studies are used to identify signaling pathways and transcription factors downstream of TGF-beta. In vivo studies allow examination of the role of these pathways in bone and cartilage. A key goal of this work is to understand the control of skeletal matrix formation and quality.
Gary Armitage D.D.S., M.S.
Dr. Armitage's current research interests include the development and testing of new methods for the diagnosis and treatment of periodontal diseases. Ongoing studies include evaluation of (1) microbial diversity in the subgingival flora, utilizing 16S ribosomal RNA gene detection techniques (in collaboration with Drs. David Relman and Paul Lepp of Stanford University); (2) salivary sialyl Lewis X in risk assessment for periodontal disease (in collaboration with Drs. Susan Fisher and Akraporn Prakobphol); (3) the effects of bisphosphonates and parathyroid hormone on mandibular bone density (in collaboration with Drs. Nancy Lane, Department of Medicine, School of Medicine, and Sharmila Majumdar, Department of Radiology, School of Medicine); (4) genetic tests for susceptibility to periodontal infections; and (5) drug-delivery systems for the treatment of periodontitis.
Research techniques routinely employed include (1) clinical research methods for the collection and analysis of periodontal examination findings; (2) gingival crevicular fluid analyses; (3) periodontal microbiology techniques such as the collection of subgingival plaque samples for microscopic, cultural, and molecular analyses; and (4) clinical trials and research study design.
Diane L. Barber Ph.D.
The Barber Lab uses genetic and biochemical approaches to study the signal transduction pathways used by hormone and growth factor receptors in regulating cell growth. Their recent focus is on receptor regulation of the GTPase family of proteins that control the organization of the actin cytoskeleton. Dynamic changes in the actin cytoskeleton play a critical role in cell growth and differentiation, and they have determined that these dynamic changes are regulated by a complex interplay between adhesion molecules of the integrin receptor family, members of the Rho family of GTPases, and plasma membrane ion exchangers. Most interesting is the novel observation that the link between adhesion receptors and cytoskeletal organization requires selective members of the family of plasma membrane Na-H ion exchangers. They found that Na-H exchangers are structurally linked to the actin cytoskeleton through their direct association with ERM proteins of the protein 4.1 superfamily of actin-binding proteins. Hence, plasma membrane ion exchangers can link the actin network to the plasma membrane and thereby convey input from adhesion molecules and GTPase signaling networks to the output of cytoskeletal reorganization. The functional significance of this interplay between integrin receptors, Rho family GTPases, and plasma membrane ion exchangers in cell contractility, migration, and proliferation is currently being investigated.
Pamela Den Besten D.D.S., M.S.
The focus of research in the Den Besten laboratory is in the biomineralization of tooth enamel and dentin. They currently have several active projects to study various aspects of enamel and dentin biomineralization. One of these projects aims to determine the mechanism by which fluoride affects enamel formation to result in enamel fluorosis. In this project they are investigating several possible mechanisms by which enamel fluorosis occurs, including altered protein/mineral interactions, and a direct of fluoride on the developing ameloblasts.
In order to determine factors that alter enamel formation, we need to better understand the proteins, proteinases and other molecules responsible for normal enamel formation. We are using immunopertrubation and antisense methods in tooth organ culture to alter the presence of certain proteins in enamel development. These studies have suggested that the enamel matrix protein, ameloblastin, has a key role in the regulation of enamel matrix synthesis.
Their studies on dentin formation have utilized various available transgenic mouse models with transgene expression driven by the osteocalcin promotor. In one of these mice models that over expresses TGF- , the dentin mineral apposition rate is increased while the physical properties of the dentin remain the same. Studies of dentin formation in these various transgenic mouse models will allow us to determine the key elements in dentin biomineralization and to use these elements to form dentin-like materials in vitro .
Rik M. Derynck Ph.D.
Research in the Derynck lab focuses on the role of transforming growth factors- and , two structurally unrelated growth and differentiation factors, in mesenchymal and epithelial cells. We use molecular, genetic cell biological and biochemical approaches to address several cell physiological and developmental questions. The work has direct relevance to many questions in orofacial development and healing and is therefore of value to the proposed NRSA.
TGF- is a growth factor for many cell types of non-hematopoietic origin and exerts its functions in an autocrine/paracrine fashion mainly in normal epithelia and in solid tumor development. It is present as a transmembrane protein at the cell surface, from which the ecodomain can be proteolytically released as a secreted polypeptide. The transmembrane form of TGF- functions as a growth factor involved in cell-cell communication. Our major projects focus on the role of the cytoplasmic domain. We specifically study its ability to interact with cytoplasmic proteins that constitute an associated protein kinase complex and its potential role as a signaling entity, as well as its function in cell physiology and development.
TGF- is a growth and differentiation factor which induces growth arrest in epithelial cells, yet stimulates proliferation in mesenchymal cells, and furthermore, is a potent inducer of extracellular matrix deposition and integrin expression. TGF- is a prototype factor for the many related differentiation factors in the TGF- superfamily. Two major lines of research are followed. In one large project, we address the mechanism of signaling of the TGF- receptors, which are transmembrane serine/threonine kinases. In the other major project, we study the role of TGF- and vgr-1, a related factor, in mesenchymal differentiation, specifically in differentiation into the muscle, bone and cartilage lineages. These developmental questions are approached in cell culture andin vivo, including transgenic models.
John D. B. Featherstone M.Sc., Ph.D.
The Featherston lab is currently involved in research in the following fields:
1.Effects of Lasers on Dental Hard Tissues
The overall objective of this research is to provide fundamental information about the effects of laser light on dental hard tissues (enamel and dentin of the teeth) in order to develop means of using lasers to a) detect early decay, b) treat teeth and modify the mineral for the prevention of the progression of dental decay.
2.Management of Dental Decay by Risk Assessment
These studies involve the application of microbiological and chemical assays of saliva as part of a risk assessment scheme to enable the management of dental decay by prevention and conservative treatment rather than conventional physical removal of decay and placement of restorations (fillings).
3.Biological mineral and protein interactions
Biological mineral is a defective calcium phosphate crystalline material. Studies of protein/mineral interactions are in progress to understand the processes of biomineralization.
NRSA trainees can participate in scientific and laboratory aspects ofany of the above areas, dependent on their background and interests.
Susan J. Fisher Ph.D.
The Fisher lab's major area of investigation is understanding adherence mechanisms used by microbial pathogens. In one project we are testing the hypothesis that bacteria which colonize the oral cavity do so by interacting with the carbohydrate portions of salivary receptors. In general, we use whole-cell ligand blotting (overlaying blots of salivary glycoproteins with bacteria) to identify interactions between individual salivary molecules and particular bacterial species. This technique led to the identification of a highly glycosylated, proline-rich glycoprotein (PRG) as the major Fusobacterium nucleatum receptor in saliva. We then determined, using mass spectrometry and nuclear magnetic resonance spectroscopy, the complete structure of the subset of PRG oligosaccharides that carry the bacterial receptor activity. We used this same experimental strategy to study the interaction between streptococci and the low-molecular-weight salivary mucin. Very recently we showed that this glycoprotein carries sulfated sialyl Lex structures and is a ligand for L-selectin. This observation has interesting implications for leukocyte trafficking in the oral cavity.
Daniel Fried Ph.D.
Optical or photonics based methods are playing an increasingly important role in medicine and dentistry by providing a means of minimally invasive diagnostics and imaging without the use of ionizing radiation. Projects include: the use of optical diagnostic tools such as optical coherence tomographic imaging, Raman scattering, IR and fluorescence imaging, and time-resolved photothermal radiometry. In order to use lasers and optical diagnostic tools safely and effectively it is important to characterize the optical properties of the tissue at the wavelengths of interest. Therefore, a major emphasis of the research of the Fried lab has been on the accurate elucidation of those properties.
Stuart Gansky DrPH
Stuart Gansky's research has concentrated on collaborative oral health research areas and its related methodological issues. Collaborative research projects have included a series of studies examining dentin, bonding, and tissue engineering; the Intergenerational Study of Adult Periodontitis (MultiPied); the Study of Chronic Pain/Temporomandibular Disorders (TMDs) in Young Women; caries risk assessment studies (one on early childhood caries and one on high risk adults); and tobacco cessation interventions.
He currently serves as Associate Director of the Biostatistics and Research Design Core of UCSF's Comprehensive Oral Health Research Center of Discovery as well as Director of the Measurement & Evaluation Core of UCSF's Center to Address Disparities in Children's Oral Health. He is PI of an NIDCR grant to develop risk assessment models for early childhood caries. Also, he is co-PI and biostatistician to study factors related to temporomandibular joint disorders and fibromylagia precursors in an established cohort of young women in which racial differences in pain reports have been found.
Barbara Gerbert Ph.D.
Dr. Gerbert has focused her research on the barriers to optimal preventive health care and the role of health care professionals. The research emphasizes the role of oral healthcare providers and primary care physicians in providing preventive care in the changing healthcare delivery system.
Deborah Greenspan B.D.S, D.Sc. (Med)
"My areas of interest include clinical, laboratory, and epidemiological studies relating to the oral manifestations of AIDS; the oral effects of cancer therapy; and the development of new therapeutic approaches for oral mucosal and salivary gland disease. I am part of a major epidemiological study of the oral lesions of HIV infection and direct a group of investigators identifying the oral lesions and providing treatment to people with these lesions.
John S. Greenspan B.D.S., Ph.D., FRCPath
My major scholarly and clinical interest for the last twenty-eight years has been the impact on the mouth and on the health sciences of HIV and AIDS. This has led to a focus on broader aspects of global health sciences, oral issues and AIDS being the most significant to me. My colleagues and I have been privileged to make contributions that have been of broad significance in the diagnosis and care of patients with HIV infection. Our contributions are indicated in my CV but I would mention that this work has brought me into contact with a wide array of people, problems and issues worldwide in academic and community health care, in basic, clinical and social/behavioral biomedical science as well as in industry. This has extended into the political arena statewide, nationally and internationally as we have sought and defended funding for research work in our field and for dental and medical research in general, for care for HIV-infected people and concerning broader issues of neglect, stigma, poverty and disparity in global health. My leadership roles in UCSF’s AIDS activities culminated in my becoming Director of the campus-wide AIDS Research Institute for the last eight years. My work has led to extensive media contact, including television, radio and the press and I have learned to respect their role in presenting our work to the public. Similarly, I have come to work with and develop mutually supportive relationships with community representatives and groups, including activists. I have been able to continue my research while assuming significant administrative responsibilities and have ventured into areas of global health beyond my original focus on oral health and on AIDS. I have been very active in the growing Global Health Sciences Program at UCSF and in the planning of the emerging UC Systemwide School of Global Health.
As Director of the UCSF AIDS Research Institute for the past eight years, indeed in most of my leadership roles, I offer a bridge between Dentistry and the other health sciences and ensure that our field both takes innovation and momentum from the mainstream while contributing to it in many ways. As Associate Dean for Global Oral Health I try to bring elements of that set of experiences and skills to bear on elevating the relevant programs of the School to their rightful place of preeminence, identify and nurture new investigators and clinician scholars in oral global health and foster new initiatives.
Richard Jordan D.D.S., Ph.D., FRCPath
Dr. Jordan is a pathologist with a research interest in oral and head and neck cancers. He is active in the Radiation Therapy Oncology (RTOG) group where he co-directs the RTOG Biospecimen Repository. The RTOG is one of 11 co-operative cancer groups that conduct large multi-institution clinical trials of cancer therapies and is responsible for several major advances in the management of head and neck, GU and brain cancers. In this capacity he serves as the pathology Chair for several clinical trials. In addition he has contributed to recent studies identifying the important role the human papilloma virus (HPV) plays in a subset of head and neck cancers. His own research is focused on understanding the molecular basis of oral cancer and its precancerous forms using novel molecular assays.
Thuan Le D.D.S., Ph.D.
Dr. Le’s 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 imperfecta. However, much is still unknown about the roles of these enamel proteins in amelogenesis.
His second clinical research project is to study the pulp revascularization of necrotic immature permanent teeth. The objective of this study is to evaluate a new clinical method for regenerating the functional development of incompletely developed permanent teeth with a diagnosis of pulpal necrosis, and to compare the clinical outcome measures to a current standard method of treatments such as calcium hydroxide or MTA apexification.
Ralph Marcucio Ph.D.
Dr. Marcucio's research program focuses on two basic science areas. First, using cutting-edge genomic technology, Dr. Marcucio is examining how the entire genome responds to orthopaedic trauma. This genome-mining approach is aimed at determining the global genome response during fracture repair and allows the possibility to generate improved, highly innovative therapies for people undergoing fracture repair. Second, Ralph is examining the role that the brain plays during normal development of the facial skeleton. Many facial birth defects have an underlying brain malformation, and the goal of the research is to generate novel therapeutic approaches that will allow correcting facial malformations prior to birth.
Rich Schneider Ph.D.
Dr. Schneider's current research program focuses on molecular and cellular mechanisms underlying development of the musculoskeletal system. He and his lab have been employing an avian chimeric transplantation system to exploit the divergent maturation rates and distinct species-specific anatomies of quail and duck. Specifically, his lab has been exchanging mesenchymal stem cells between quail and duck embryos, which challenges resultant chimeras to assimilate donor versus host-specific differences in growth and morphology. Using this approach, his lab has been identifying genes and signaling interactions that regulate the timing of musculoskeletal tissue differentiation, control size and shape, and which ultimately enable cartilage, bone, and muscle to achieve structural and functional integration. A goal of Dr. Schneider's research is to devise molecular-based therapies for inducing repair and regeneration of musculoskeletal tissues affected by congenital defects, disease, and trauma.
Caroline Shiboski D.D.S., M.P.H., Ph.D.
Dr. Shiboski is the principal investigator of the Oral HIV/AIDS Research Alliance (OHARA) UCSF site, which is the Epidemiology Unit of this multicenter grant and is part of the AIDS Clinical Trial Group Network (ACTG). She is currently involved with several OHARA research protocols that are being implemented in ACTG sites in the US, Africa, India, and Peru. Dr. Shiboski is also the lead Epidemiologist in the Sjögren’s Syndrome International Collaborative Clinical Alliance (SICCA), a project aimed both at establishing new classification criteria for Sjögren’s Syndrome and at developing a data and biospecimen repository for this disease.
Osamu Tetsu MD
Dr Tetsu has benefited from extensive training in cancer and molecular biology after a residency in general and abdominal surgery. Dr Tetsu receives his MD and his PhD in Japan and moved to the United States in 1997 for postdoctoral training with Dr Frank McCormick. Since then, Dr Tetsu has discovered that cyclin D1 is a b-catenin target gene (Nature 398, 1999) and that CDK2 kinase activity is dispensable in cancer cells (Cancer Cell 3, 2003). In addition, Dr Tetsu collaborated with his colleagues and identified causative genes in the MAPK signaling pathway in cardiofaciocutaneous syndrome (Science 311, 2006; Hum Mol Genet 17, 2008). Moreover, Dr Tetsu found that cyclin D1 degradation is mediated by phosphorylation at Thr286 through the MAPK signaling cascade and the FBXW8, which is an E3 ligase (PLoS One 1, 2007). Recently, Dr Tetsu is focusing his research interests in adenoid cystic carcinoma (ACC) of the salivary glands, and identified cross-contamination and misidentification of ACC cell lines (PLos One 4, 2009), and has discovered inactivation of c-Kit signaling in ACC tumors in collaboration with Dr Richard Jordan (Neoplasia 12, 2010).
Torsten Wittmann Ph.D.
Dr. Wittmann's laboratory focuses on the function and spatiotemporal regulation of the microtubule cytoskeleton during complex cell behaviors. Microtubules are polymers that frequently switch between polymerization and depolymerization. These non-equilibrium dynamics may allow microtubule ends to explore the cytoplasm to interact with specific intracellular targets. We are interested in a fascinating group of proteins that are defined by their dynamic localization to growing microtubule ends in cells. The functions of these +TIPs are not well understood. In addition, it is quite mysterious how +TIPs recognize growing microtubule ends, and microtubule association of certain +TIPs is spatiotemporally regulated in cells. We use biochemical and cell biological techniques in combination with live cell confocal microscopy to examine how these and other cytoskeletal proteins determine cell behavior in different experimental model systems. This includes planar polarized keratinocytes that directionally migrate at the edge of epithelial cell sheets, apical-basal polarized epithelial cells in a three-dimensional extracellular matrix, and endothelial cells that establish planar polarity in response to fluid shear stress.
