BAYLOR´S SCIENTIFIC TRAINING PROGRAM FOR DENTAL ACADEMIC RESEARCHERS: B-STARS
N Rena, Professor And Head
Texas A&m University Health Science Ctrcity: College Station country: United States (us)
Grant 5T32DE018380-04 from National Institute Of Dental & Craniofacial Research
Abstract: This is a new NRSA Institutional Research Training Grant (T32) application for Baylor´s Scientific Training Program for Dental Academic Research Scholars (B-STARS). The application is in direct response to the revised training initiatives of the NIDCR and requests (i) Continued support for a highly successful short-term program for the training of dental research scholars. The program has been intensified to increase the commitment of trainees toward academic research careers by early identification and continued engagement in research throughout dental school; (ii) New funding for an integrated dual-degree DDS/PhD program. This program was initiated through institutional funds and a successful series of NIDCR Individual Predoctoral Dentist Scientist Fellowships (F30 awards); and (iii) Support for a well-crafted series of short- and long-term postdoctoral training experiences for faculty and fellows. These programs will provide the skills needed to address new opportunities in craniofacial research. B-STARS draw from the expanding scientific, intellectual and physical resources at Baylor College of Dentistry (BCD). A full spectrum of research training opportunities is enhanced by new institutional initiatives and NIDCR R24/U24 awards for the enhancement of research infrastructure at BCD. Strategic alliances with UT Southwestern Medical Center (UTSW), Texas A&M´s Institute of Biosciences and Technology (IBT), Rice University, and the hiring of new BCD researchers have led to the selection of a team of 52 outstanding faculty mentors. This group offers interdisciplinary training in the following focus research areas Genes and Development; Matrix Biology and Tissue Engineering; Neurosciences and Molecular Pathology; and Clinical Research. BCD´s participation in an NIH Roadmap K12 and CTSA awards to UTSW offers multidisciplinary training to B-STARS Clinical Research Scholars. A highly innovative and integrative core and discipline-specific curriculum with journal clubs, seminars and research symposia will facilitate an exchange of information among students and faculty in various disciplines and allow each trainee to acquire extensive critical thinking skills. Graduate trainees of B-STARS will be able to (a) interpret new scientific information from an insightful perspective and teach with scholarly credibility; (b) engage in knowledgeable dialog with student and faculty clinicians; (c) lead cutting-edge craniofacial, dental and oral biology research in NIH and other extramural research programs; (d) publish reports in peer reviewed journals; and (e) sustain successful careers in academic dentistry. B-STARS benefits from unequivocal institutional support and dynamic leadership. A program evaluation plan will critically assess the success of the training program on the development of future dental academicians. The leadership team of B-STARS is committed to work with the NIDCR to improved performance and outcomes that will develop the best practices for the training, education and career development of dentist-scientists
Keywords: Dental; Research Personnel; Training Programs
Project start date: 2008-07-01
Project end date: 2012-06-30
Budget start date: 1-JUL-2011
Budget end date: 30-JUN-2012
PFA/PA: PAR-05-101
5T32DE018380-04 (2011): $423189
Sponsored Links Excellgen http://Excellgen.com
Grants awarded to N Rena
SELF-ASSEMBLING PEPTIDE NANOFIBER HYDROGELS FOR DELIVERY OF PROTEINS AND CELLS
N Rena
Rice Universitycity: Houston country: United States (us)
Grant 1R01DE021798-01A1 from National Institute Of Dental & Craniofacial Research
Abstract: This proposal develops a nanostructured mimic of extracellular matrix prepared from a self-assembling peptide we call "Multidomain Peptides" or MDPs. The MDPs self-assemble into nanofibers that can be triggered to form a hydrogel. Because the peptides are easy to prepare and have a well defined design criteria many variations on the MDP architecture can be prepared which allow us to tailor 1) the conditions under which the fibers self-assemble (including conditions compatible with cell culture and in vivo applications), 2) the mechanical properties critical for handling and injectability, 3) the presentation of chemical information for cells, and 4) controlled biodegradation. This exceptional combination of properties will be developed here to create biomimetic scaffolds for the entrapment and delivery of cells, proteins and small molecule drugs. Our work will culminate with an in vivo application which uses this nanostructured hydrogel for dental regeneration. It is expected that the nanofibers will prove to be suitable as an injectable, localized, simultaneous delivery method for cells, proteins and small molecule drugs which will actively assist in directing cellular activity. Finally, after the MDP matrix has played its role it will degrade leaving behind only regenerated tissue. Such a matrix will play a critical role in future tissue engineering strategies (including, but not limited to, dental regeneration) which require a smart scaffolding material to organize the constituent cells and drugs until the body´s own regenerative ability can take over. Our proposal is organized into four aims. Aim 1 will determine the design, flexibility and methods used to prepare MDP nanofibers. Aim 2 will optimize MDP nanofibers for three dimensional cell entrapment, cell delivery and cell mediated biodegradation. Aim 3 will develop a series of nanofibrous gels which will deliver growth factors and other small molecules localized in time and space. Aim 4 will test the above developed nanofibrous hydrogels ability to promote dental regeneration in vivo. This highly translational research will apply novel tissue engineering and nanotechnology concepts to the design of multidomain peptide hydrogels intended as an all-purpose scaffold for the regeneration tissue (tested here on the regeneration of the dentin-pulp complex). By combining expertise in chemistry, materials sciences, nanotechnology, cell biology and clinical dentistry we will generate data that will provide the framework for further studies testing these hydrogels in human clinical trials. One of the most exciting areas of medical research is tissue engineering which promises to supplement our own regenerative ability to allow us to replace or re-grow damaged or diseased tissues and organs. Researchers use appropriate cell lines, growth factors and drugs which are organized by a synthetic matrix. In this proposal we describe an interdisciplinary approach to the design and optimization of a nanostructured matrix made from synthetic proteins. This matrix will entrap cells, proteins and drugs and allow them to be delivered together by syringe to the site necessary
Keywords: Amino Acid Sequence; Amino Acid Substitution; Architecture; Area; base; Biodegradation; Biomimetics; Cell Adhesion; Cell Culture Techniques; Cell Line; Cell Proliferation; Cells; Cellular biology; Charge; Chemicals; Chemistry; Clinical; Clinical Trials; Complex; controlled release; crosslink; Cues; Data; Dental; Dental Pulp; Dentin; Dentistry; design; Encapsulated; Engineering; Environment; Extracellular Matrix; Fiber; flexibility; Future; Gel; Goals; Growth Factor; Height; Human; Hydrogels; in vivo; in vivo regeneration; Injectable; interdisciplinary approach; Ionic Strengths; Left; Length; Mechanics; Mediating; Medical Research; Methods; Mus; nano; nanofiber; nanostructured; Nanostructures; Nanotechnology; Natural regeneration; novel; Organ; Peptides; Pharmaceutical Preparations; Play; programs; Property; Proteins; Recovery; regenerative; Research Personnel; response; Role; scaffold; Science; self assembly; Series; Site; small molecule; Stem cells; success; Surface; synthetic protein; Syringes; Testing; Time; Tissue Engineering; tissue regeneration; Tissues; Tooth structure; Translational Research; Transplantation; Variant; Width; Work
Relevance: One of the most exciting areas of medical research is tissue engineering which promises to supplement our own regenerative ability to allow us to replace or re-grow damaged or diseased tissues and organs. Researchers use appropriate cell lines, growth factors and drugs which are organized by a synthetic matrix. In this proposal we describe an interdisciplinary approach to the design and optimization of a nanostructured matrix made from synthetic proteins. This matrix will entrap cells, proteins and drugs and allow them to be delivered together by syringe to the site necessary
Project start date: 2011-12-01
Project end date: 2016-11-30
Budget start date: 1-DEC-2011
Budget end date: 30-NOV-2012
1R01DE021798-01A1 (2012): $383170
REGULATION OF RUNX2 FUNCTION BY TWIST-1 IN TOOTH DEVELOPMENT
N Rena, Professor And Head
Texas A&m University Health Science Ctrcity: College Station country: United States (us)
Grant 5R01DE013368-08 from National Institute Of Dental & Craniofacial Research
Abstract: In this competing renewal, we propose to continue our research on the role of Runx2 in tooth development. Data from our work in the previous award period indicated key roles for Runx2 in directing the fate of Dental epithelium during morphogenesis and in controlling the onset of odontoblast differentiation. Our studies point to the critical need to learn how Runx2 activities are precisely regulated during tooth morphogenesis and cell differentiation and whether its role in these processes is modulated through interactions with other molecules. The nuclear protein Twist-1 is of particular interest as a regulatory protein partner for Runx2. Our rationale for studying if Runx2, a cell differentiation factor, interacts with Twist-1, a cell survival factor, is derived from studies in our and other laboratories that suggest that these interactions between Runx2 and Twist-1 occur at the protein level. Our experiments will directly test the hypothesis that Runx2´s key functions in odontoblast differentiation are regulated by Twist-1 at the level of protein- protein interactions that are functionally antagonistic in nature. The selective and transient blocking of Runx2 function by Twist-1 provides a means to restrain odontoblast differentiation until morphogenesis is complete. We further propose that interactions between Runx2 and Twist-1 are not mutually antagonistic as Twist-1 can mediate cell proliferation during morphogenesis via FGF-mediated epithelial mesenchymal signaling. Hence, the presence of supernumerary teeth in human CCD and accessory buds in Runx2(-/-) mice likely reflect increased activity of Twist-1 rather than a direct effect of decreased levels of Runx2. Aim 1 will determine if the patterns of Runx2 and Twist-1 (mRNA and protein) expression are compatible with their proposed partnership during tooth development and will correlate these patterns with the expression of molecular markers of tooth morphogenesis and odontoblast differentiation. Aim 2 will assess with mouse genetic loss-of-function and gain-of-function approaches whether alterations in Twist-1 expression affects tooth morphogenesis and odontoblast differentiation. Aim 3 will study the molecular basis of Runx2 - Twist-1 protein interactions in Dental mesenchyme and the functional consequences of this interaction on Runx2 functions in odontoblast differentiation, and Aim 4 will test whether the bHLH domain of Twist-1 can mediate tooth morphogenesis via FGF-signaling that is independent of its interactions with Runx2. These studies will increase our understanding of how Runx2 achieves its selective functions in tooth development through its partnership with Twist-1. Importantly, they will explain how supernumerary teeth form and if odontoblast differentiation is determined by the release of an inhibition. Such data will also provide a framework for understanding the pathogenesis of Cleidocranial Dysplasia and Saethre-Chotzen Syndrome, 2 human genetic disorders that threaten dentition
Keywords: 2-cyclopentyl-5-(5-isoquinolylsulfonyl)-6-nitro-1H-benzo(D)imidazole; acrocephalosyndactly type III; acrocephalosyndactyly III; acrocephalosyndactyly III (ACS III); Address; Affect; Apoptosis; Apoptosis Pathway; Assay; Autoregulation; Award; base; bHLH Domain; Bioassay; Biochemical; Biologic Assays; Biological Assay; biological signal transduction; Boxing; calcification; Cell Communication and Signaling; Cell Death, Programmed; Cell Differentiation; Cell Differentiation process; Cell Growth in Number; Cell Line; Cell Lines, Strains; Cell Multiplication; Cell Proliferation; Cell Signaling; Cell Survival; Cell Viability; CellLine; Cellular Proliferation; Chotzen syndrome; Classification; cleidocranial digital dysostosis; cleidocranial dysostosis; Cleidocranial Dysplasia; cleidocranial dysplasia (CCD, CLCD); compound-1; craniocleidodysostosis; Craniosynostosis; cultured cell line; Data; Defect; Dental; Dental Papilla; Dental Pulp; Dental Pulp Calcification; Dentin; Dentition; Development; DNA Binding Domain; dysostosis cleidocranialis; dysostosis cleidocraniodigitalis; dysostosis cleidocraniopelvina; dysostosis craniofacialis with hypertelorism; dysostosis generalisata; Dysostosis, Cleidocranial; dysplasia cleidocranialis; dysplasia cleidofacialis; Epithelial; Epithelium; experiment; experimental research; experimental study; Fontanelle; gain of function; gene product; Genes; Genetic; Genetic Alteration; Genetic Change; Genetic Condition; Genetic defect; Genetic Diseases; genetic disorder; genetic regulatory protein; genome mutation; Goals; Hereditary Disease; hereditary disorder; Heterozygote; Homeostasis; Human; Human Genetics; Human, General; Incisor; incisor (dental); interest; Intracellular Communication and Signaling; Investigators; Laboratories; Learning; loss of function; Mammals, Mice; Man (Taxonomy); Man, Modern; Marie-Sainton syndrome; Mediating; Mesenchymal; Mesenchymas; Mesenchyme; Messenger RNA; Mice; Molecular; Molecular Disease; Molecular Genetic; Molecular Genetics; molecular marker; Morphogenesis; mRNA; Murine; Mus; Mutation; mutational dysostosis; Nature; Nuclear Extract; Nuclear Protein; Nuclear Proteins; Odontoblasts; Organ; osteoblast differentiation; osteodental dysplasia; osteodental dysplasia (ODD); Pathogenesis; pathway; Pathway interactions; Pattern; pelvicocleidocranial dysostosis; Phenotype; Physiological Homeostasis; Process; programs; Programs (PT); Programs [Publication Type]; protein expression; Protein Motifs, DNA-Binding; protein protein interaction; Proteins; pulp; pulp calcification; Regulation; regulatory gene product; Regulatory Protein; Research; Research Personnel; research study; Researchers; RNA, Messenger; Role; Saethre-Chotzen syndrome; Saethre-Chotzen syndrome (SCS); Scheuthauer-Marie-Sainton syndrome; Signal Transduction; Signal Transduction Systems; Signaling; social role; Staging; Structure of fontanel of skull; Supernumerary Tooth; Syndrome, Saethre-Chotzen; synostosis (cranial); Systematics; teeth; Testing; Tooth; Tooth structure; Work
Project start date: 1999-08-01
Project end date: 2011-05-31
Budget start date: 1-JUN-2009
Budget end date: 31-MAY-2011
5R01DE013368-08 (2009): $257097