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CRADA and Collaboration Opportunities

Opportunities listed below include current and past projects relevant to research conducted within the intramural program at NIDCR.  Prospective collaborators are evaluated based on their unique capabilities or resources, past history of agreements with NIDCR, including license, collaborative, confidentiality, and material transfer agreements, and other criteria that may be specific to a given opportunity. Respondents to specific CRADA and Collaborative Opportunities should state their unique capabilities enabling fulfilment of the research objectives. 

1701 AAV biology and vectors for gene therapy

Laboratory of Dr. John Chiorini, tel 301.496.4279
All inquiries, contact the Director, Office of Technology Transfer and Innovation Access: 
David W. Bradley, PhD, bradleyda@nidcr.nih.gov  

Keywords
Adeno-associated virus (AAV), Gene therapy

Description  
The overall research goal of the AAV Section is to define the interactions of adeno-associated virus (AAV) with its target cell. Our hypothesis is that by understanding these interactions as they apply to the biology of the virus, we can contribute to the use of AAV vectors for gene therapy. The Molecular Physiology and Therapeutics Branch’s program on gene transfer considers AAV vectors to be the most useful vector for long-term clinical studies with many tissues. Ongoing areas of investigation include the mechanism by which the viral regulatory proteins alter the cellular environment in order to make it permissive for the viral life cycle.  Other projects involve understanding and modifying the cellular tropism and cell-capsid interaction that define the biodistribution and transduction activity of vectors based on AAV. The laboratory is seeking collaborations to investigate the role of AAV expression, particle assembly, AAV/DNA, and AAV capsid/cell interaction.

Selection Criteria

Collaborator must have 

  • Expertise in large scale AAV vector production
  • Expertise in gene transfer technology
  • Expertise in AAV Biology
  • Resources and expertise for the manufacturing of clinical grade AAV vector

Announcement Date

  • January 4, 2017

 

1602 AAV biology and gene therapy for the treatment of Sjögren’s syndrome

Laboratory of Dr. John Chiorini, tel 301.496.4279
All inquiries, contact the Director, Office of Technology Transfer and Innovation Access: 
David W. Bradley, PhD, bradleyda@nidcr.nih.gov  

Keywords
Adeno-associated virus (AAV), Gene therapy, Sjögren’s syndrome

Description  
The overall research goal of the AAV Biology Section is to define the interactions of adeno-associated virus (AAV) with its target cell. Our hypothesis is that by understanding these interactions as they apply to the biology of the virus, we can contribute to the use of AAV vectors for gene therapy. The Molecular Physiology and Therapeutics Branch’s program on gene transfer to the salivary gland considers AAV vectors to be the most useful vector for long-term clinical studies with this tissue. One ongoing area of investigation addresses the mechanism by which the viral regulatory proteins alter the cellular environment in order to make it permissive for the viral life cycle. The laboratory is seeking collaborations to investigate the role of AAV regulatory protein expression and protein/DNA interactions as they relate to AAV biology.

Selection Criteria

C ollaborator must have:

  • Expertise in large scale baculovirus production as related to AAV vector production.
  • Expertise in AAV structural analysis
  • T-cell assays for analysis of local and systemic impact on immune function
  • Metabolomic expertise and sample analysis
  • Resources and expertise for the manufacturing of clinical grade AAV vector

Announcement Date

  • March 3, 2016


1502 AAV-based gene therapy methods applied to glandular diseases

Laboratory of John Chiorini, tel 301-496-4279
All inquiries, contact the Director, Office of Technology Transfer and Innovation Access, NIDCR
David William Bradley, PhD, bradleyda@nidcr.nih.gov 

Keywords
Bauhin's glands, anterior lingual glands, Ciaccio's glands, accessory lacrimal glands, Cobelli's glands, Ebner's glands, Esophageal glands, Fränkel's glands, Henle's glands, Krause's glands, Meibomian gland, Moll's glands, Olfactory glands, Bowman's glands, Gley's glands, Sandstroem's glands, parathyroid gland, Parotid gland, Sublingual gland, Rivini's gland, Submandibular gland, Sudoriparous glands, Boerhaave's glands, Suzanne's gland, Weber's glands, Glands of Zeis, Salivary glands.

Description
The laboratory directed by Dr. Jay Chiorini has developed an AAV-based gene therapy method to express candidate target genes locally within glandular tissues and validated the approach using several candidate targets genes (Lee et al., 2012, Roescher et al., 2012, Vosters et al., 2012, Yin et al., 2012, Roescher et al., 2014). The laboratory is seeking collaborations to establish proof-of-concept that AAV delivery to secretory organs in mouse models can support experimental assays that screen potential therapeutic deliverables and validate the experimental and therapeutic approach.  Glands in the head and neck are of particular interest.

Selection Criteria
Candidates will be selected on the basis of:

  • Identified disease models relevant to NIDCR’s mission
  • Establishment of a therapeutic candidate appropriate for AAV delivery
  • Expertise in selection of AAV serotypes, promotors and vector genomes
  • Expertise in verification of expression and analysis of mice at physiological, cellular and molecular levels.

 Announcement Date

  • September 11, 2015 

 

1501 Hyperphosphatemic familial tumoral calcinosis/hyperostosis-hyperphosphatemia syndrome

Laboratory of Dr. Michael Collins, tel 301.496.4913
All inquiries, contact the Technology Development Coordinator:
David Bradley, PhD, bradleyda@nidcr.nih.gov 
 
Keywords
fibroblast growth factor 23 (FGF23), N-acetylgalactosaminyltransferase-T3 (GALNT3), 1,25-dihydroxyvitamin D3, Hyperphosphatemic familial tumoral calcinosis/hyperostosis-hyperphosphatemia syndrome (FTC/HHS)

Description
Hyperphosphatemic familial tumoral calcinosis/hyperostosis-hyperphosphatemia syndrome (FTC/HHS) is an autosomal recessive disorder caused by mutations in either fibroblast growth factor 23 (FGF23), KLOTHO, or UDP-GalNAc:polypeptide N-acetylgalactosaminyltransferase-T3 (GALNT3).  Patients with FTC/HHS have a deficiency of, resistance to FGF23, resulting in high blood levels of phosphate due to increased renal tubular absorption of phosphate and elevated or inappropriately normal 1,25-dihydroxyvitamin D3.  The net effect is an increase in the calcium x phosphate product, which promotes the development of ectopic calcifications.  NIDCR is interested in developing collaborations to better understand the onset and progression of ectopic calcifications.

Selection Criteria
Candidates will be evaluated on their expertise in rare diseases, capability in GMP manufacturing of biologics, and interest in funding projects related to FTC/HHS.

Announcement Date

  • February 23, 2015

 

1403 Cellular and Molecular Characterization of Primary Sjögren’s Syndrome Samples

Laboratory of Ilias Alevizos, tel 301.496.6207
MOLECULAR PHYSIOLOGY & THERAPEUTICS BRANCH, NIDCR
All inquires: contact the Technology Development Coordinator:
David Bradley, PhD, bradleyda@nidcr.nih.gov

Keywords
Sjogren’s Syndrome (SS), xerostomia, saliva, massspectrometric detection

Description
The scope of this collaborative opportunity is to correlatespecific lymphocyte populations, cytokine presence, autoantibodies and othersecreted molecules to clinical phenotypes typical of Primary Sjögren’s syndrome(pSS) to better understand the alterations of the immune system and itsinteractions with salivary gland epithelial cells. pSS is an autoimmune disease marked bydiversity in clinical phenotype: pSS primarily involves the salivary and lachrymal glands, for example, butcan also involve other organ systems. Similar to other autoimmune diseases, pSSprimarily affects women. Beforehypotheses can be tested regarding the underlying mechanisms, a bettercharacterization of pSS at the cellular and molecular level is required.
A variety of clinical phenotypes will be correlated withsalivary epithelial cell behavior lymphocyte subtypes, whole blood, salivarygland biopsies and saliva will be utilized to better understand the dynamicinteractions among the various cell types involved in the development andprogression of this disease. Additionally, search of novel autoantibodies willbe performed for biomarker and clinical trial endpoint development.
NIDCR will provide clinical samples, including blood,saliva, and tissues, as part of the collaboration.

Selection Criteria
Collaborator will be selected on a variety of criteria:

  • Ability to perform Flow Cytometric analysis, RNA extraction,Quantitative gene expression analysis, ELISAs, Multiplex panels and arrays.
  • Knowledge of Sjogren's Syndrome (SS) and autoimmune disease.

Announcement Date

  • Posted May 29, 2014

 

1402 Cdk5 Inhibitors for Analgesic Use

Laboratory of Ashok Kulkarni, tel 301.435.2887
All inquires, contact the Technology Development Coordinator:
David Bradley, PhD, bradleyda@nidcr.nih.gov

Keywords
Cdk5, serine/threonine protein kinase, cyclin-dependent kinases, dorsal root ganglia, vanilloid 1

Description
Cdk5 is a proline-directed serine/threonine protein kinase that belongs to the family of cyclin-dependent kinases. It is expressed in all tissues, but it is functionally active mainly in the neurons where its activators, p35 and p39, are predominantly expressed. Dr. Kulkarni’s laboratory and others have previously reported that expression of Cdk5 and p35, as well as Cdk5 kinase activity, was increased in the dorsal root ganglia (DRG) and the spinal cord (SC) after peripheral-inflammation. Elevated Cdk5 activity phosphorylates transient receptor potential vanilloid 1 (TRPV1), a key receptor that modulates agonist-induced calcium influx in the neurons. These findings suggest that Cdk5 plays an important role in the molecular mechanisms involved in pain signaling.

Dr. Kulkarni’s laboratory is seeking collaborators that can provide Cdk5 inhibitors to test this hypothesis. The collaboration is expected to provide valuable insights into the potential of these inhibitors as analgesics to treat painful conditions.

Selection Criteria
Candidates will be evaluated on their basis to provide Cdk5 inhibitors with characteristics amenable for use as analgesics. CDk5 inhibitors will be evaluated according to their:

  • Degree of characterization, in vitro and in vivo
  • Pre-clinical and clinical toxicology data, if available
  • Efficacy in inhibition of CDk5, or other protein kinases as appropriate
  • Knowledge of design strategies for small molecule inhibitors of protein kinases

Announcement Date

  • November 12, 2014

 

1401 Development of AAV Vectors for Salivary Gene Transfer

Laboratory of John Chiorini, tel 301-496-4279
All inquires, contact the Technology Development Coordinator:
David Bradley, PhD, bradleyda@nidcr.nih.gov

Keywords
xerostomia, head and neck cancer, radiation

Description
Each year approximately 35,000-40,000 patients develop head and neck cancers in the USA, with about 500,000 cases worldwide. In industrialized countries, the treatment of most such patients includes ionizing radiation (IR). A significant consequence of this IR treatment is the irreversible damage to salivary glands in the IR field. There is no adequate conventional treatment for this condition. The focus of this collaborative research opportunity will be to 1) test the safety of gene transfer of a specific water channel locally to the salivary glands of radiation induced xerostomia patients in a phase 1 clinical trial, 2) follow changes in salivary flow as a result of the addition of this channel to salivary gland cells of these patients 3) developed optimized vectors for gene transfer to the salivary gland.

Selection Criteria
Candidates will be evaluated on the basis of:

  • Experience with clinical trials.
  • Experience with vector production and development of gene therapy production.
  • Track record of success in regulatory affairs.
  • Proprietary technology related to gene therapy.
  • Experience with development of therapeutic proteins.

Announcement Date

  • Posted October 23, 2013

 

1307 Hepcidin Role in Injected MSC Benefit

Laboratory of Dr. Eva Mezey tel 301-435-5635
All inquires, contact the Technology Development Coordinator:
David Bradley, PhD, bradleyda@nidcr.nih.gov

Keywords
salivary glands, irradiation, gene therapy

Description
Mesenchymal Stem Cells (i.e. Bone marrow stromal cells), known as MSCs derived from mouse and human bone marrow have anti-inflammatory and anti-microbial properties. NIDCR found that they produce a protein called hepcidin, which has been isolated from fish and shown to have anti-microbial properties in addition to its well-known role in the homeostasis of red blood cells. NIDCR wants to study if this MSC derived hepcidin has a role in the beneficiary effect of injected MSCs in a variety of infectious conditions (such as peritonitis; hepatitis; colitis). NIDCR will perform in vitro studies to induce and measure the hepcidin production of MSCs in response to bacterial toxins and use them in vivo in mice to see if efficiency can be improved.. The laboratory of Dr. Eva Mezey, within the National Institute of Dental and Craniofacial Research (NIDCR) at the National Institutes of Health (NIH) is seeking collaborations in the field of MSC derived hepcidin effect on infectious disease.

Selection Criteria
Collaborator(s) will be evaluated on the basis of:

  • Development of Antibodies to hepcidin, human and mouse specific
  • Characterization of hepcidin antibodies
  • Sensitivity and specificity of assays to measure hepcidin

Announcement Date

  • Posted August 26, 2013

 

1306 Exploration of Gene therapy to Protect Salivary Glands from Irradiation Damage

Laboratory of Matthew Hoffman, tel 301-496-1660
All inquires, contact the Technology Development Coordinator:
David Bradley, PhD, bradleyda@nidcr.nih.gov

Keywords
salivary glands, irradiation, gene therapy

Description
More than 500,000 patients worldwide/year are treated for head and neck cancer and treatment usually involves therapeutic irradiation. The salivary glands are often in the field of irradiation and suffer permanent loss of secretory function, which impairs the oral health and affects patient quality of life. The reason the hypofunction is permanent is presumed to be due to a defect in progenitor cell function. NIDCR showed that parasympathetic nerves are a crucial component of the progenitor cell niche during gland development as they maintain a pool of keratin 5+ progenitors for organogenesis (Knox et al, Science 2010). Injured adult organs do not regenerate after parasympathectomy, and there are few treatments to improve organ regeneration. The laboratory of Dr. Matthew Hoffman, within the National Institute of Dental and Craniofacial Research (NIDCR) at the National Institutes of Health (NIH) is seeking collaborations in the field of organ regeneration and post therapeutic irradiation recovery

Selection Criteria
Collaborator(s) will be evaluated on the basis of:

  • Advanced clinical experience with protective and regenerative genes
  • Delivery of genes to relevant organs in clinical and/or animal model experimental settings
  • Pre-clinical experience in the selection, operational maintenance, and experimental manipulation of selected animal models

Announcement Date

  • Posted July 29. 2013

 

1305 Substrate Specificities of Oral Microbial Glycoside Hydrolases

Laboratory of John Cisar, tel 301-496-1822
All inquires, contact the Technology Development Coordinator:
David Bradley, PhD, bradleyda@nidcr.nih.gov

Keywords
streptococci , salivary glycans, glycoside hydrolases

Description
Oral streptococci produce an array of different glycoside hydrolases that act on salivary glycans to liberate nutrients for biofilm growth and development. Putative glycoside hydrolases have been identified from whole genome sequences of Streptococcus oralis Uo5, S. gordonii Challis or S. sanguinis SK36. Enzymes will be overexpressed, purified as His-tagged proteins and tested for their abilities to degrade different fluorescently-labeled oligosaccharide substrates ranging in size from a linear trisaccharide to a complex biantennary oligosaccharide consisting of 9 sugar residues with fucose residues linked α1-2, α1-3 and α1-4 on the antennae. This approach will help determine oligosaccharide substrate specificities of glycoside hydrolases produced by oral microorganisms that grow and in saliva and form dental plaque.

Selection Criteria
Candidates will be evaluated on their basis of:

  • Access to or ownership of characterized oligosaccharide substrates
  • Expertise in fluorescently labeling oligosaccharide substrates
  • Expertise in examining substrate specificities of these proteins using a panel of fluorescently labeled oligosaccharide substrates
  • Manufacturing capability and ability to supply sufficient materials for the collaboration

Announcement Date

  • Posted July 17, 2013

 

1304 Biomarkers for Sjogren’s Syndrome

Laboratory of Dr. Ilias Alevizos, Tel 301-496-6207
MOLECULAR PHYSIOLOGY & THERAPEUTICS BRANCH, NIDCR

All inquires: contact the Technology Development Coordinator:
David Bradley, PhD, bradleyda@nidcr.nih.gov

Keywords
Sjogren’s Syndrome (SS), xerostomia, saliva, mass spectrometric detection

Description
Laboratory of Dr. Ilias Alevizos is seeking collaborators to provide expertise in identifying and characterizing small molecules in saliva. Saliva is an important and complex fluid that is produced by the human body. It is made up primarily of water, but also includes a variety of proteins, sugars and salts. It serves many purposes including defeating bacteria and viruses, keeping the mouth wet so that food can be tasted and swallowed, detoxifying some molecules found in plants, and breaking down starches to improve absorption of energy. There are also many components in saliva whose function is not well understood. The analysis may lead to the discovery of better methods to diagnose Sjogren’s Syndrome (SS) patients. Additionally, a more complete understanding of composition of saliva may also lead to development of a treatment for xerostomia.

References

  1. The majority of microRNAs detectable in serum and saliva is concentrated in exosomes. Gallo A, Tandon M, Alevizos I, Illei GG. PLoS One. 2012;7(3):e30679. Epub 2012 Mar 9.
  2. MicroRNA expression profiles as biomarkers of minor salivary gland inflammation and dysfunction in Sjögren's syndrome. Alevizos I, Alexander S, Turner RJ, Illei GG. Arthritis Rheum. 2011 Feb;63(2):535-44.
  3. MicroRNAs as biomarkers in rheumatic diseases. Alevizos I, Illei GG. Nat Rev Rheumatol. 2010 Jul;6(7):391-8. doi: 10.1038/nrrheum.2010.81. Epub 2010 Jun 1.

Selection Criteria
Collaborator must have:

  • demonstrated competence in providing analysis of saliva samples using liquid chromatography with mass spectrometric detection (LC-MS);
  • developed software useful to compare sample compositions with an aim of identifying markers within Saliva;
  • expertise in identifying the chemical nature of the ions;
  • the ability to (or through contract) synthesize appropriate amino acid sequences and perform controls confirming that the synthetic and salivary ions have identical properties

Announcement Date

  • May 6, 2013

 

1303 Light devices for Photobiomodulation

Laboratory of Dr. Praveen Arany, Tel: 301-496-3561
Cell Regulation and Control Unit, Oral and Pharyngeal Cancer Branch, NIDCR.

All inquires: contact the Technology Development Coordinator:
David Bradley, PhD, bradleyda@nidcr.nih.gov

Keywords
Photobiomodulation, Lasers, LED, Light devices, low level light therapy.

Description
The laboratory of Dr. Praveen Arany is seeking collaborations with companies able to provide devices to study Photobiomodulation (PBM). These include broad light sources, LEDs and lasers. Photobiomodulation is the biological response of low level light therapy, within specific dose regimens, to stimulate or inhibit a process with an therapeutic outcome. This is distinct from the other known phototherapy modalities such as photodynamic therapy or Psoralen UV therapy. The major purpose of PBM is to relieve pain and inflammation while inducing a healing-regenerative response. Dr. Arany’s research has uncovered one of the molecular mechanisms of PBM involving the activation of a latent growth factor, TGF-β that can promote oral wound healing and direct stem cell differentiation. His lab in NIDCR will explore the precise biophysical and biochemical events involved in this process as well as exploring other molecular pathways mediating PBM. Besides the basic science component, his lab will be focused on developing safety and efficacy protocols for PBM-LLLT for clinical translation via clinical trial protocols at the clinical center.

References
1. Arany PR. Photobiomodulation: Poised form the Fringes Photomed Laser Surg. 2012, 30; 9:507-509. PMID: 22779706
2. Arany PR, Nayak RS, Hallikerimath S, Limaye AM, Kale AD and Kondaiah P. Activation of Latent TGF-β1 by low power laser in vitro correlates with increased TGF-β1 levels in laser enhanced oral wound healing. Wound Repair and Regeneration 2007; 15; 6; 866-874.
PMID: 18028135
3. Chen AC*, Arany PR*, Tompkinson EM, Saleem T, Mooney DJ, Yull FE, Blackwell TS, Hamblin MR. Low level light therapy activates NF-kB via generation of reactive oxygen species in mouse embryonic fibroblasts. PLOS One 2011;6 (7):e22453 PMID: 21814580

Selection Criteria
Candidates will be evaluated on the following criteria(s):

  • Provide devices with well characterized parameters including wavelengths, fluence, irradiance, timing controls, pulsed versus continuous modes of operation;
  • Ability to actively contribute to design specification changes requested by investigators; 
  • Established expertise in pursuing FDA clearance for clinical translation.

Announcement Date

  • Posted March 15, 2013

 

1302 Development of Chemopreventive Treatments for Head and Neck Squamous Cell Carcinoma


All inquires, contact the Technology Development Coordinator:
David Bradley, PhD, bradleyda@nidcr.nih.gov

Keywords
rapamycin, head and neck squamous cell carcinoma (HNSCC), mTOR

Background
This laboratory is seeking collaborations with pharmaceutical companies able to develop and commercialize a technology that describes a method of potentially preventing or treating HNSCC through the inhibition of mTOR activity. The proof of this principle was demonstrated by rapid regression of mouth tumors in mice afflicted with Cowden syndrome with the administration of rapamycin. Like HNSCC, development of this disease is linked to over activation of the Akt/mTOR pathway.

Description
The therapeutic potential of rapamycin was demonstrated using mice in experiments that model chronic exposure to tobacco, which promotes the development of HNSCC. Therefore, inhibitors of mTOR have considerable potential in the prevention and treatment of HNSCC. Using a local, sustained-release oral drug delivery system for early intervention to prevent potentially malignant or premalignant lesions developing into HNSCC, could deliver the inhibitors of mTOR with reduced systemic side effects and a lower required drug dose.

Selection Criteria
Candidates will be evaluated on based on the following characteristic(s):

  • Collaborator must submit an exclusive license application to the NIH Office of Technology Transfer
  • Collaborator must have an accepted exclusive license application with the NIH Office of Technology Transfer

Announcement Date

  • Posted November 2, 2012

 

1301 The Use of Specialized PNA (Peptide Nucleic Acid) Probes to Examine Bacterial Species in Plaque and Tissue Biopsies

Laboratory of Dr. Niki Moutsopoulos, tel 301-435-7182
All inquires, contact the Technology Development Coordinator:
David Bradley, PhD, bradleyda@nidcr.nih.gov

Keywords

PNA probes, immune dysfunction, bacteria

Background
The laboratory of Dr. Niki Moutsopoulos, within the National Institute of Dental and Craniofacial Research (NIDCR) at the National Institutes of Health (NIH) is seeking collaborations with pharmaceutical companies able to provide specialized PNA probes to be used examine the prevalence of bacterial species in plaque and tissue biopsies in patients with genetic immune deficiencies. PNA probes are similar to DNA probes, but their backbone is composed of peptide bonds. Due to the lack of charged phosphate groups and electrostatic repulsion PNA probes bind stronger to DNA. This allows for the design of shorter and very specific probes that is essential for accurate detection of individual species of bacteria.

Description
Studies have revealed that the microbial biofilms in patients with genetic immune deficiencies is quite complex. However, the special relationship between host and bacterial cells is not fully understood. The use of specialized PNA probes to indentify bacterial species associated/responsible for immune pathology in patients with immune dysfunction could provide vital information in the pathogenesis of these diseases. Past studies in in vitro systems have demonstrated the sensitivity and specificity of PNA probes for oral bacteria.

Application

  • Collect biopsy tissue in patients with genetic immune defects and healthy volunteers.
  • Transcriptomic/proteomic analysis will be performed on tissue.
  • FISH studies will be done to identify microbial colonization.
  • Specialized PNA probes will be used examine the prevalence of bacterial species in plaque and tissue biopsies in patients with genetic immune deficiencies.

Selection Criteria
Candidates will be evaluated on based on the following characteristic(s):

  • Company must have extensive knowledge in developing PNA probes.
  •  Company must be able to assist in FISH protocol development and implementation.

Announcement Date

  • Posted October 19, 2012 

 

1207 The Effectiveness of Various Ceramic Scaffolds in the Formation of High Quality Bone and Marrow Tissue

Laboratory of Dr. Pamela Robey, tel 301-496-4563
All inquires, contact the Technology Development Coordinator:
David Bradley, PhD, bradleyda@nidcr.nih.gov

Keywords
bone marrow stromal cells (BMSCs), ceramic scaffolds, bone, marrow

Background
The laboratory of Dr. Pamela Robey, within the National Institute of Dental and Craniofacial Research (NIDCR) at the National Institutes of Health (NIH) is seeking collaborations with pharmaceutical companies able to provide ceramic scaffolds to be used for the transplantation of human bone marrow stromal cells into immunocompromised mice. Standard histochemical techniques will be used to determine the formation of bone and support of marrow, and compared between ceramic scaffolds. The ceramic scaffolds should also be able to be resorbed in a reasonable amount of time.

Description
It has been shown that when human bone marrow stromal cells (BMSCs) are transplanted with an appropriate scaffold in vivo, they have the ability to form not only bone, but also stroma that supports blood formation and marrow adipocytes (bone marrow). Consequently, these cells show a great deal of promise for use in human patients who have lost large segments of bone due to trauma and disease. However, the scaffold that is used greatly influences the growth and differentiation of the cells. After extensive testing, it is apparent that human BMSCs have a preference for ceramic scaffolds that are composed of minerals similar to the naturally occurring mineral in bone (a carbonate-rich hydroxyapatite). However, not all ceramic scaffolds are supportive of even bone formation, and currently available ceramic scaffolds are only slowly resorbed, if at all.
 
Application

  • Human bone marrow stromal cells will be isolated from surgical waste and mixed with heat sterilized ceramic particles.
  • Mixture will then be transferred to subcutaneous pockets created in the back of immunocompromised mice.
  • Standard histochemical techniques will be used to determine the formation of bone and marrow in transplanted sections.

Selection Criteria
Candidates will be evaluated on based on the following characteristic(s):

  • Company must have extensive knowledge in developing ceramic scaffolds.
  • Ceramic scaffolds must support the formation of bone and stroma and perform better than proprietary material tested in house at NIDCR.
  • Ceramic scaffolds must be resorbed in a reasonable amount of time.

Announcement Date

  • Posted September 24, 2012

 

1206 Monitoring the Pharmacodynamic Effects of Immunomodulatory Agents after Treatment with Immunotherapeutic Drugs in Patients with Sjogren’s Syndrome (SS)

Laboratory of Gabor Illei, tel 301-496-4072
All inquires, contact the Technology Development Coordinator:
David Bradley, PhD, bradleyda@nidcr.nih.gov 

Keywords
Sjogren’s Syndrome, immunomodulatory agents, Th cells

Description
The laboratory of Gabor Illei, within the National Institute of Dental and Craniofacial Research (NIDCR) at the National Institutes of Health (NIH) is seeking collaborations with pharmaceutical companies who are able to provide a biologic that modulates the immune system. This biologic needs to have a direct effect on T cell subsets (e.g., TReg, TH1, TFH, TH17) in order for the cause of inflammation in SS patients to be targeted and assessed. The pharmaceutical company must also be able to provide in situ hybridization (ISH) data on the T cell subsets.
Sjogren’s Syndrome (SS) is an autoimmune disease characterized by extensive lymphocytic infiltration into the salivary and lacrimal glands of patients. A majority of the infiltrates are CD4+ T helper (Th) cells, and are believed to play a crucial role in the pathogenesis of SS. The CD4+ Th cell population is comprised of functionally distinct cellular subsets characterized by specific patterns of cytokines and transcription factors. In order better understand the immunological basis of SS at the tissue level, in situ hybridization (ISH) techniques can be used. The ISH technology has been shown to be a highly sensitive and specific means of detecting T cell subsets along with cell specific cytokines, chemokines and transcription factors. Previous IHC studies were performed on SS patients who were treated with Efalizumab, a humanized anti-CD11a mAb. Results indicated that there is significant decrease in CD4+FoxP3+ cells within the salivary gland compared to placebo controlled samples. More detailed analysis of CD4+ Th cell subsets and the cytokine profile within the tissue specimens were not performed on these samples at that time.

Application

  • Detect T cells subsets using in situ hybridization (ISH) technology before and after treatment of the biologic in minor salivary gland lip biopsies taken from patients with SS.
  • Detect pharmacodynamic changes within the salivary glands of SS patients following treatment of the biologic

Selection Criteria
Candidates will be evaluated on the basis of:

  • Ability to provide a biologic that has a direct effect on T cell subsets and proven ability to restore immune tolerance
  • Extent of pre-clinical data set supporting the MOA.
  • Overseeing development and completion of ISH studies on T cell subsets.
  • Capability of developing a technique for quantitative analysis of the cells such that pharmacodynamic effects of the biologic can be determined.
  • synthesis of novel probes to the various targets

Announcement Date

  • Posted July 27, 2012

 

1205 Restoration of Parathyroid and Renal Calcium Response with a Calcilytic Drug

Laboratory of Dr. Michael Collins, tel 301-496-4913
All inquiries, contact the Technology Development Coordinator:
David Bradley, PhD, bradleyda@nidcr.nih.gov

Keywords
hypoparathyroidism, calcilytic

Description
The laboratory of Dr. Michael Collins is seeking collaborations with companies able to provide to provide a calcilytic drug for use in clinical studies of hypoparathyroidism. One of the forms of hypoparathyroidism is autosomal dominant hypoparathyroidism (ADH), caused by activating mutations of the calcium-sensing receptor (CaR). The CaR is a G-protein-coupled receptor that when activated by binding to its ligand, elemental calcium, and through Gqα/phospholipase C signaling inhibits parathyroid gland PTH release. Calcilytics are a class of molecules that are antagonists of the CaR, and which have been shown in vitro to reverse the effects of mutations in the CaR that are responsible for ADH. In theory calcilytics represent a class of drugs that may be dramatically effective in the treatment of ADH, the form of hypoparathyroidism which is associated with the most morbidity and is the most difficult to treat.

Selection Criteria
Candidates will be evaluated on their basis of their ability to provide a calcilytic drug with the following characteristic(s):

  • Sufficient quantities of pharmaceutical grade drug and placebo, or GMP manufacturing capability, for using drug in clinical trials
  • Prior phase I safety and/or efficacy experience with the drug
  • CRO support for the clinical trial, including, for example, protocol development, monitoring, and patient travel

Announcement Date(s) 

  • Posted July 12, 2012
  • Modified on July 16, 2012
  • Closed March 15, 2013

 

1204 Identifying and Characterizing Salivary Gland Stem/Progenitor Cells

Laboratory of Matthew Hoffman, tel 301-496-1660
All inquires, contact the Technology Development Coordinator:
David Bradley, PhD, bradleyda@nidcr.nih.gov

Keywords
salivary glands, Fgf10, mice

Description
The laboratory of Dr. Matthew Hoffman, within the National Institute of Dental and Craniofacial Research (NIDCR) at the National Institutes of Health (NIH) is seeking collaborations with pharmaceutical companies able to provide the Fgf10 null allele, found within the mouse model, in order to identify and characterize the stem/ progenitor cell populations that are involved in forming the salivary glands during development and maintain adult salivary function. Mice lacking the Fgf10 allele will be used for standard breeding and timed mating to determine the effect of Fgf10 gene dosage on Fgf signaling. 

Publications:
1) Min et al, Genes Dev. 12: 3156-3161, 1998.
2) Metzger et al, Nature, 453(7196): 745-750, 2008.

Selection Criteria
Candidates will be evaluated on the basis of:

  • Ability to provide Fgf10 allele within cross bred mice containing other altered genes, such as Spry1/2 and Fgf7.

Announcement Date

  • Posted May 10, 2012

 

1203 Ability of Tempol to protect salivary glands function in patients undergoing radio/chemotherapy

Translational Research Core, Dr. Indu Ambudkar, tel 301-496-5298
All inquires, contact the Technology Development Coordinator:
David Bradley, PhD, bradleyda@nidcr.nih.gov

Keywords
Tempol, radiotherapy, chemotherpay, dry mouth, oral cancer.

Description
Over the last ten years Dr. Ana Cotrim has demonstrated that the stable nitroxide Tempol (4-hydroxy-2,2,6,6-tetramethylpiperidine-1-oxyl), is able to selectively protect normal tissues from the insults of radiation and chemotherapy. Different routes of administration, including: intraperitoneal, intramuscular, subcutaneous and topical, were able to prevent the onset of salivary dysfunction in mice treated with head and neck irradiation mimicking the radiotherapy scheme patients receive. Topical application of Tempol was also able to protect the mucosa of mice treated with radiation in addition to cisplatin, a chemotherapy drug.

The Translational Research Core is seeking collaborations with a company that has been able to develop a tempol formulation for mouth rinse use, masking its flavor and color. Also, the company should have the interest in developing a clinical trial to evaluate tempol and its ability to protect normal tissue from the radiation and chemotherapy treatments.

Selection Criteria
Candidates will be evaluated on their basis of:

  • Ability to formulate tempol mouth rinse
  • Ability to conduct a clinical trial using tempol for protection of normal tissue during radio/chemotherapy
  • Familiarity of writing and submitting FDA clinical trial proposals

Announcement Date

  • Posted December 27, 2011

 

1202 Development of small molecule inhibitors for the treatment of Sjogren’s syndrome. 

Laboratory of John Chiorini, tel 301-496-4279
All inquires, contact the Technology Development Coordinator:
David Bradley, PhD, bradleyda@nidcr.nih.gov

Keywords
Sjogren’s syndrome, BAFF inhibitors

Description
The laboratory of Dr. John Chiorini is seeking collaborations with a company with expertise in the development of novel small molecule inhibitors targeting B cell activating factor (BAFF).

BAFF belongs to the TNF family [also known as BLyS (B lymphocyte stimulator)], and is a vital homeostatic cytokine for B cells that helps regulate both innate and adaptive immune responses. BAFF is a crucial survival factor for transitional and mature B cells, and is a promising therapeutic target for autoimmune disorders. BAFF is associated with systematic lupus erythematosus (SLE)-like autoimmune disorders and induces rheumatic arthritis in a transgenic mouse model. BAFF levels are also high in human serum from patients with autoimmune diseases such as rheumatic arthritis, autoimmune diabetes, Sjogren's syndrome and multiple sclerosis. Inhibitors of BAFF are currently being evaluated for treatment of Sjogren’s syndrome.

Selection Criteria

Candidates will be evaluated on the basis of:

  • Experience with development of small molecule inhibitors.
  • Experience in development of second and third generation molecules.
  • Experience with molecular modeling and computational approaches for drug design
  • Access to manufacturing of select compounds in sufficient quantities for in vivo testing

Announcement Date

  • Posted November 2, 2011

 

1201 RANK and RANKL in the Pathogenesis of Fibrous Dysplasia of Bone

Laboratory of Dr. Michael Collins, tel 301-496-4913
All inquires, contact the Technology Development Coordinator:
David Bradley, PhD, bradleyda@nidcr.nih.gov

Keywords
Fibrous dysplasia, bone marrow stromal cells, osteoprotegerin, osteoclastogenesis

Description
The laboratory of Dr. Michael Collins is seeking collaborations with companies able to provide antibodies or other inhibitors against RANK and RANKL. Fibrous dysplasia of bone (FD) is a benign fibroosseous lesion that results from activating mutations in Gsα that lead to increased intracellular levels of cAMP with resultant proliferation of bone marrow stromal cells (BMSCs). Elevated markers of bone metabolism is one of the hallmarks of the disease (1,2), and sections of FD tissue have shown that osteoclasts are prominent, suggesting that FD BMSC-mediated osteoclastogenesis may be important in the disease (3). Given the importance of the osteoprotegerin - receptor activator of nuclear factor kappa-β - receptor activator of nuclear factor kappa-β ligand pathway (OPG/RANK/RANKL) in osteoclastogenesis (4-6), and the role of cAMP in this pathway (7), there is reason to suspect that activation of this pathway may be important in either the development, establishment and/or expansion of FD lesions. In support of this concept, is the fact that in in vitro studies FD BMSCs show higher level of RANKL expression (8). NIDCR plans to investigate the levels of these proteins in archival FD tissue sections and related materials to see if there is support for the hypothesis that this pathway is activated and potentially involved in the pathogenesis of FD.

To better assess the role of this pathway in FD, NIDCR plans to look for the presence of members of the pathway (RANK, and RANKL) in FD tissues, as well as ex vivo and in vitro models of FD and related tissues and controls.

1. Collins MT, Chebli C, Jones J, Kushner H, Consugar M, Rinaldo P, Wientroub S, Bianco P, Robey PG 2001 Renal phosphate wasting in fibrous dysplasia of bone is part of a generalized renal tubular dysfunction similar to that seen in tumor-induced osteomalacia. J Bone Miner Res 16(5):806-13. 2. Collins MT, Kushner H, Reynolds JC, Chebli C, Kelly MH, Gupta A, Brillante B, Leet AI, Riminucci M, Robey PG, Bianco P, Wientroub S, Chen CC 2005 An instrument to measure skeletal burden and predict functional outcome in fibrous dysplasia of bone. J Bone Miner Res 20(2):219-26. 3. Riminucci M, Kuznetsov SA, Cherman N, Corsi A, Bianco P, Gehron Robey P 2003 Osteoclastogenesis in fibrous dysplasia of bone: in situ and in vitro analysis of IL-6 expression. Bone 33(3):434-42. 4. Simonet WS, Lacey DL, Dunstan CR, Kelley M, Chang MS, Luthy R, Nguyen HQ, Wooden S, Bennett L, Boone T, Shimamoto G, DeRose M, Elliott R, Colombero A, Tan HL, Trail G, Sullivan J, Davy E, Bucay N, Renshaw-Gegg L, Hughes TM, Hill D, Pattison W, Campbell P, Sander S, Van G, Tarpley J, Derby P, Lee R, Boyle WJ 1997 Osteoprotegerin: a novel secreted protein involved in the regulation of bone density. Cell 89(2):309-19. 5. Dougall WC, Glaccum M, Charrier K, Rohrbach K, Brasel K, De Smedt T, Daro E, Smith J, Tometsko ME, Maliszewski CR, Armstrong A, Shen V, Bain S, Cosman D, Anderson D, Morrissey PJ, Peschon JJ, Schuh J 1999 RANK is essential for osteoclast and lymph node development. Genes Dev 13(18):2412-24. 6. Lacey DL, Timms E, Tan HL, Kelley MJ, Dunstan CR, Burgess T, Elliott R, Colombero A, Elliott G, Scully S, Hsu H, Sullivan J, Hawkins N, Davy E, Capparelli C, Eli A, Qian YX, Kaufman S, Sarosi I, Shalhoub V, Senaldi G, Guo J, Delaney J, Boyle WJ 1998 Osteoprotegerin ligand is a cytokine that regulates osteoclast differentiation and activation. Cell 93(2):165-76. 7. Kondo H, Guo J, Bringhurst FR 2002 Cyclic adenosine monophosphate/protein kinase A mediates parathyroid hormone/parathyroid hormone-related protein receptor regulation of osteoclastogenesis and expression of RANKL and osteoprotegerin mRNAs by marrow stromal cells. J Bone Miner Res 17(9):1667-79. 8. Piersanti S, Remoli C, Saggio I, Funari A, Michienzi S, Sacchetti B, Robey PG, Riminucci M, Bianco P 2010 Transfer, analysis, and reversion of the fibrous dysplasia cellular phenotype in human skeletal progenitors. J Bone Miner Res 25(5):1103-16.

Selection Criteria
Candidates will be evaluated on their basis of their ability to provide antibodies with the following characteristic(s):

  • Antibodies must be against RANK or RANKL
  • Antibodies must have demonstrated sensitivity in immunohistochemical staining, Western blotting, and flow cytometry

Announcement Date

  • Posted November 1, 2011
  • Modified August 21, 2017

 

1106 Development of Anti-BMP6 therapeutics for the treatment of Sjogren’s Syndrome.

Laboratory of John Chiorini, tel 301-496-4279
All inquires, contact the Technology Development Coordinator:
David Bradley, PhD, bradleyda@nidcr.nih.gov

Keywords
Sjogren’s syndrome, bone morphogenic protein 6 (BMP6), RNAi inhibitors

Description
The laboratory of Dr. Chiorini is seeking collaborations with a company with expertise in the development of RNAi or protein based inhibitors. The molecules will be used to test the affect of BMP6 on the development of Sjogren’s syndrome in preclinical studies at the National Institutes of Health.

In its primary form, Sjogren syndrome is defined as the presence of disorders in the above organs without additional connective tissue diseases. The prevalence of SS is second only to that of rheumatoid arthritis. The mechanism(s) driving this disorder are poorly understood and may involve a combination of environmental and genetic factors. In addition to a loss of secretory activity in several epithelial cell types, autoantibodies, mononuclear infiltrates in the secretory epithelia, increased apoptosis, and elevated proinflammatory cytokines have been reported in SS patients.

In order to better understand changes in the secretory epithelia associated with the loss of gland activity, we performed microarray analysis on RNA isolated from the minor salivary glands of SS patients and observed a significant increase in expression of the bone morphogenic protein 6 (BMP6). Over expression of BMP6 locally in the salivary glands of normal mice resulted in the loss of salivary gland activity in these mice as well as fluid movement in either isolated primary acinar cells or cells cultured in the presence of BMP6. In addition changes in the connective tissue of the gland and distribution of the tight junction proteins were observed.

Application

  • RNAi based inhibitors will be used to treat patients suffering from Sjogren’s syndrome.
  • Said inhibitors will be administered in a dose-dependent manner and patients’ salivary gland activity response to the inhibitors will be assessed using microarray analysis

Selection Criteria
Candidates will be evaluated on the basis of:

  • The ability to develop, in silico models, and screen compounds that, based on silico modeling, will have modulating properties against the modeled targets.

Announcement Date

  • Posted October 5, 2011

 

1105 Regulation of B7 family as potential intervention strategy in Sjögren’s syndrome

Laboratory of Dr. Sharon Wahl, tel 301-496-4178
All inquires, contact the Technology Development Coordinator:
David Bradley, PhD, bradleyda@nidcr.nih.gov

Keywords
Chitinase, Sjögren’s, B7 family, macrophage, exocrine gland

Description
Dr. Sharon Wahl’s laboratory recently demonstrated that expression of Chitinase in Sjögren’s patients’ minor salivary glands correlates with severity of the disease and immunopathology. Increased Chitinases were shown during an in vitro human monocyte/macrophage differentiation assay and in response to IFN (Wild, T. et al., 2011)

B7-H4 (also referred to as B7x or B7S1), a member of the B7 family (Prasad 2003; Sica 2003; Zang 2003), is a checkpoint molecule that functions to suppress T-cell activation/proliferation and differentiation. The receptor for B7-H4 (B7-H4-R) has not yet been identified. B7-H4 does not bind to known CD28 family members such as CD28, CTLA-4, ICOS, and PD-1 (Sica 2003). A recombinant Fc fusion protein, B7-H4Ig, composed of the extracellular domain (ECD) of human B7-H4 fused to the hinge and Fc region of human IgG1, would be useful for the treatment of autoimmune diseases including Sjögren’s syndrome.

Under this collaboration, the effect of the recombinant Fc fusion protein on human monocytes/macrophages will be studied; the goal being to provide proof-of-concept data to translate B7-H4Ig into an intervention strategy for Sjögren’s patients.

References
Greenwell-Wild T, Moutsopoulos NM, Gliozzi M, Kapsogeorgou E, Rangel Z, Munson PJ, Moutsopoulos HM, Wahl SM. Chitinases in the salivary glands and circulation of patients with Sjögren's syndrome: Macrophage harbingers of disease severity. Arthritis Rheum. 2011 Oct;63(10):3103-15. doi: 10.1002/art.30465.
 
Selection Criteria
Candidates will be evaluated on their basis of:

  • Ability to make and provide a recombinant Fc fusion protein, B7-H4Ig, composed of the extracellular domain (ECD) of human B7-H4 fused to the hinge and Fc region of human IgG1
  • Expertise and knowledge regarding how the recombinant Fc fusion protein binds human monocytes/macrophages

Announcement Date(s)

  • Posted October 5, 2011
  • Closed March 15, 2013

 

1104  A Novel Use of a Calcimimetic Drug: Treating Fibroblast Growth Factor 23 (FGF23)-mediated Hypophosphatemia

Laboratory of Dr. Michael Collins, tel 301-496-4913
All inquires, contact the Technology Development Coordinator:
David Bradley, PhD, bradleyda@nidcr.nih.gov
 
Keywords
Fibroblast growth factor, drugs, hypophosphatemia
 
Description
The laboratory of Drs. Michael Collins and Rachel Gafni is seeking collaborations with pharmaceutical companies able to provide analytical reference standards for FDA-approved calcimimetic drugs. Reference standards will be used to test the purity and potency of calcimimetic capsules formulated by the National Institutes for use in clinical research studies.

Chronic hypophosphatemia due to renal phosphate wasting leads to rickets and osteomalacia. While hypophosphatemia may be due to a variety of acquired conditions, there are several genetic phosphate-wasting conditions caused by pathological elevations in the phosphaturic hormone, fibroblast growth factor 23 (FGF23)(1). Affected individuals may suffer from skeletal deformity, pain, decreased activity tolerance, short stature, and dental disease, even with aggressive treatment from birth. The mainstay of therapy is high-dose oral phosphate in multiple doses per day and vitamin D analogues. Unfortunately, this regimen is associated with several potential complications including diarrhea, hyperparathyroidism with exacerbation of renal phosphate losses, and medullary nephrocalcinosis. Additionally, treatment with phosphate and biologically active vitamin D analogues has been shown to increase circulating FGF23 levels, further intensifying phosphate wasting and thus limiting treatment effect.

The calcium-sensing receptor (CaSR) is a cell-surface receptor found primarily on parathyroid and renal cells. Its function is to detect the ambient calcium level and act accordingly to maintain serum calcium within the relatively narrow normal range. Activation of the CaSR decreases parathyroid hormone (PTH) secretion, with a subsequent decrease in serum calcium(2). Studies have suggested that the phosphaturic effect of FGF23 is dependent upon the presence of PTH(3, 4). Therefore, suppression of PTH secretion in patients with FGF23-mediated hypophosphatemia may increase tubular reabsorption of phosphate (TRP) and serum phosphate(5-7).

Application

  • Treat patients suffering from FGF23-mediated phosphate wasting disorders with a calcimimetic drug.
  •  Said calcimimetic drug will not result in the complications associated with current treatment and be administered in a dose-dependent manner.

References

1. Bastepe M, Juppner H 2008 Inherited hypophosphatemic disorders in children and the evolving mechanisms of phosphate regulation. Rev Endocr Metab Disord 9:171-180
2. Trivedi R, Mithal A, Chattopadhyay N 2008 Recent updates on the calcium-sensing receptor as a drug target. Curr Med Chem 15:178-186
3. Collins MT, Lindsay JR, Jain A, Kelly MH, Cutler CM, Weinstein LS, Liu J, Fedarko NS, Winer KK 2005 Fibroblast growth factor-23 is regulated by 1alpha,25-dihydroxyvitamin D. J Bone Miner Res 20:1944-1950
4. Gupta A, Winer K, Econs MJ, Marx SJ, Collins MT 2004 FGF-23 is elevated by chronic hyperphosphatemia. J Clin Endocrinol Metab 89:4489-4492
5. Geller JL, Khosravi A, Kelly MH, Riminucci M, Adams JS, Collins MT 2007 Cinacalcet in the management of tumor-induced osteomalacia. J Bone Miner Res 22:931-937
6. Alon US, Levy-Olomucki R, Moore WV, Stubbs J, Liu S, Quarles LD 2008 Calcimimetics as an adjuvant treatment for familial hypophosphatemic rickets. Clin J Am Soc Nephrol 3:658-664
7. Yavropoulou MP, Kotsa K, Gotzamani Psarrakou A, Papazisi A, Tranga T, Ventis S, Yovos JG 2010 Cinacalcet in hyperparathyroidism secondary to X-linked hypophosphatemic rickets: case report and brief literature review. Hormones (Athens) 9:274-278

Selection Criteria
Candidates will be evaluated on their basis of:

  • Ability to provide calcimimetic drug reference standards
  • FDA Approval Status of calcimimetic drugs

Announcement Date

  • Posted September 13, 2011

 

1103 The Role of the ECM Components Biglycan (bgn) and Fibromodulin (fmod) in Osteoclast Formation and Function

Laboratory of Marian Young, tel 301-496-8860
All inquires, contact the Technology Development Coordinator:
David Bradley, PhD, bradleyda@nidcr.nih.gov

Keywords
biglycan, fibromodulin, osteopenia, osteoporosis 

Description
The laboratory of Dr. Marian Young is seeking collaborations with pharmaceutical companies able to provide a drug that is known to have an effect on the regulation of post-natal bone mass . Mice with specific mutations in extracellular matrix genes that have low bone mass will be given this drug and monitored for the ability to rescue and repair the low bone mass (osteopenia). The drug should be effective to specifically control the activity of bone resorbing cells, the osteoclasts.

Biglycan (bgn) and fibromodulin (fmod) are members of the small leucine-rich proteoglycan family and previously shown to control bone mass (1) osteoarthritis (2) and ectopic ossification of tendon (3). They are prominent components of the extra-cellular matrix (ECM) and are made by bone marrow stromal cells, maturing osteoblasts and osteocytes. In data unpublished so far we found the bones from the bgn/fmod KO mice develop severe osteopenia by 2 months of age. The effect on bone mass can even be seen by 1 month of age however no obvious effects of bgn/fmod depletion were found during development. Tetracycline-calcein double labeling showed the bgn/fmod depleted mice did not have less bone formation and in fact there was a slight trend towards increased MAR. Static histomorphometry confirmed that the trabecular bone was severely diminished in the bgn/fmod KO femurs. The number of TRAP positive cells was increased 3 fold in bgn/fmod KO bones indicating that an increase in osteoclastogenesis likely causes the decreased bone mass observed in this model.

Application 

  • Administer reagent to mice suffering from osteopenia (low bone mass).
  •  Monitor the formation and steady state mass of the bones of X-ray, microCT and histology.

Publications
1) Xu, T, et al, Nature Genetics 20:78-82, 1998.
2) Embree et al, Am J Pathol. 176(2): 812-26, 2010
3) Bi et al Nature Medicine, 13:1219-27, 2007.

Selection Criteria
Candidates will be evaluated on the basis of:

  • Ability to provide Fc fragments of (osteoprotogerin) OPG effective in the regulation of osteoclastogenesis
  • Fc fragments of OPG must be provided in sufficient quantities for multiple assays in vivo
  • OPG Fc reagent must be effective for use on genetically altered mice

Announcement Dates

  • Posted September 2, 2011
  • Closed November 16, 2011

 

1102 Functional Significance of eIF5A isoforms in cell proliferation, apoptosis and cancer

Laboratory of Myung Hee Park, tel 301-496-5056
All inquires, contact the Technology Development Coordinator:
David Bradley, PhD, bradleyda@nidcr.nih.gov
 
Keywords
eIF5A, hypusine , deoxyhypusine synthase (DHS), deoxyhypusine hydroxylase (DOHH).

Description
eIF5A is the only protein containing hypusine which is formed posttranslationally by two enzymes, deoxyhypusine synthase (DHS) and deoxyhypusine hydroxylase (DOHH). Hypusine modification is essential for the activity of eIF5A in cell proliferation. In mammals, two isoforms of eIF5A exist. Enhanced expression levels of either eIF5A-1 and/or eIF5A-2 (hypusinated forms) was reported in various human cancer tissues or cancer cells, suggesting an important role for hypusinated eIF5A in cell proliferation and transformation. NIDCR will use various adenoviral vectors encoding eIF5A-1, eIF5A-2 wild type or mutant forms (truncated or point mutation) prepared in Collaborator’s laboratory and transduce them alone or together with vectors encoding DHS and DOHH to overexpress unhypusinated eIF5A precursor or hypusinated eIF5A isoforms in HeLa and head and neck cancer cell lines, to determine the effects of them on cell growth and tumorigenicity. NIDCR will also use single or combination of adenoviral vectors in animal tumor model of head and neck cancer.

Selection Criteria
Candidates will be evaluated on their basis of:

  • Ability to make adenoviral vectors expressing eIF5A isoforms and their mutant forms
  • Specialized expertise in the application of the adenoviral vectors in cultured cells and animals.
  • Knowledge of functional importance of overexpression of eIF5A isoforms in cancer

Announcement Date

  • Posted  September 1, 2011

 

1101 How does chewing gum effect initial supragingival biofilm?

Laboratory of John Cisar, tel 301-496-1822
All inquires, contact the Technology Development Coordinator:
David Bradley, PhD, bradleyda@nidcr.nih.gov

Keywords
Chewing gum, oral composition formulations, dental plaque

Description
Dental caries and periodontal disease are closely associated with the oral biofilm known as dental plaque.  Much is known about the bacterial species composition of this biofilm, especially at its early stage (up to 12 hrs following tooth cleaning).  The primary initial colonizers are streptococci, actinomyces, and veillonellae.  Many representatives of these genera participate in specific cell-cell binding interactions: a protein adhesin on the surface of one binding partner recognizes cell-surface receptor polysaccharides (RPS) on strepococci; various RPS exist that are chemically similar but functionally distinct.  The binding interaction, termed coaggregation, relies on an in vitro assay; coaggregation profiles are known for a wide range of oral bacterial isolates. Despite the potential significance of coaggregation in formation of plaque, little is known about cell-cell recognition within oral biofilms in situ.  The objective is to determine the influence of the increased salivary flow that occurs when an individual chews gum on the spatial organization of bacteria within undisturbed dental plaque.

Selection Criteria
Candidates will be evaluated on their basis of:

  • Specialized expertise in formulation of oral consumer products
  • Manufacturing capability and ability to supply sufficient materials for the collaboration
  • Familiarity with FDA regulations governing food products

Announcement Date(s)

  • Posted March 25, 2011
  • Updated August 26, 2011
  • Closed September 29, 2011
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This page last updated: October 31, 2017