National Institute of Diabetes and Digestive and Kidney Diseases

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Building 12A, Room 3011
12 South Drive (MSC 5362)
Bethesda, MD 20892-5632
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Lab Profile
Tech Transfer Website: 
http://techdev.niddk.nih.gov/

Description

The National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) supports a wide range of medical research through grants to universities and other medical research institutions across the country. The Institute also supports government scientists who conduct basic, translational and clinical research across a broad spectrum of research topics and serious, chronic diseases and conditions related to the institute's mission. In addition, the NIDDK supports research training for students and scientists at various stages of their careers and a range of education and outreach programs to bring science-based information to patients and their families, health care professionals and the public.

Mission

The National Institute of Diabetes and Digestive and Kidney Diseases conducts and supports research on many of the most serious diseases affecting public health. The Institute supports much of the clinical research on the diseases of internal medicine and related subspecialty fields as well as many basic science disciplines. The Institute's Division of Intramural Research encompasses the broad spectrum of metabolic diseases such as diabetes, inborn errors of metabolism, endocrine disorders, mineral metabolism, digestive diseases, nutrition, urology and renal disease, and hematology. Basic research studies include biochemistry, nutrition, pathology, histochemistry, chemistry, physical, chemical, and molecular biology, pharmacology, and toxicology. NIDDK extramural research is organized into divisions of program areas:

  • The Division of Diabetes, Endocrinology, and Metabolic Diseases;
  • The Division of Digestive Diseases and Nutrition; and
  • The Division of Kidney, Urologic, and Hematologic Diseases.

The Division of Extramural Activities provides administrative support and overall coordination. A fifth division, the Division of Nutrition Research Coordination, coordinates government nutrition research efforts.

The Institute supports basic and clinical research through investigator-initiated grants, program project and center grants, and career development and training awards. The Institute also supports research and development projects and large-scale clinical trials through contracts.

Technology Disciplines

Technologies
Displaying 1 - 10 of 51
 
A Mouse Model for Systemic Inflammation in Glucocerebrosidase-Deficient Mice with Minimal Glucosylceramide Storage
Description:
Gaucher disease, the most common lysosomal storage disease, is an inherited metabolic disorder in which harmful quantities of the lipid glucocerebroside accumulate in the spleen, liver, lungs, bone marrow and in rare cases in the brain, due to a deficiency of the enzyme glucocerebrosidase (Gba) that catalyses the first step in the biodegradation of glucocerebrosides. Type 1 Gaucher disease is the most common and is distinguished from the other forms of the disease, types 2 and 3, by the lack of neurologic involvement. The clinical features of Type 1 are heterogeneous, vary broadly in clinical severity and affect many organ systems. The major disease manifestations include enlarged spleen and liver, bone lesions, hematologic abnormalities and lung involvement. The disease has also been associated with a sustained inflammatory reaction. Gaucher disease is most prevalent in the Ashkenazi Jewish population with an incidence of approximately 1 in 450 persons while in the general public the incidence is 1 in 100,000. There are an estimated 30,000 Gaucher disease patients world-wide with approximately 3000 patients currently receiving enzyme replacement therapy which has been shown to be highly effective in treatment of the disease. The cost of therapy is approximately $100,000-$300,000 annually and is a life-long treatment, which makes the case for affordable new therapies urgent.
Details
Internal Lab Reference ID
E-256-2003/0
Inventors
Richard Proia
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A Mouse with a Targeted Mutation in the Uncoupling Protein-3 (upc3) Gene
Description:
The NIH announces the development of a transgenic mouse with a targeted mutation in the ucp3 gene. The ucp3 gene is implicated I the function of regulating energy metabolism. This regulatory function is thought to be accomplished by changing metabolic efficiency (causing energy expended as heat rather than used for ADP/ATP conversion) and/or by participating in fat metabolism. The mutation should inactivate the ucp3 function and the mouse provided a testing vehicle for the above hypotheses.
Patent Abstract
The NIH announces the development of a transgenic mouse with a targeted mutation in the ucp3 gene. The ucp3 gene is implicated I the function of regulating energy metabolism. This regulatory function is thought to be accomplished by changing metabolic efficiency (causing energy expended as heat rather than used for ADP/ATP conversion) and/or by participating in fat metabolism. The mutation should inactivate the ucp3 function and the mouse provided a testing vehicle for the above hypotheses. If in fact ucp3 is involved in energy efficiency and/or fat metabolism, then variation in its sequence or level of expression may explain some of human obesity. If ucp3 is involved in fever generation, it would be of interest in testing inactivating drugs. In summary, this mouse model provides a model for evaluating the role of ucp3 in obesity, energy efficiency, and selective use of energy sources (i.e. fat vs. carbohydrates), body temperature regulation, such as fever, or other forms of stimulated thermogenesis (e.g. by diet of dietary fat). For example, a drug candidate thought to act via ucp3 should have no effect in these mice. Marc Reitman (NIDDK)➽ more inventions... Research Tool -- patent protection is not being pursued for this technology Admin. Licensing Specialist (ALS), Email: Phone: E-031-1999/0 Updated:Jun 16, 2010
Details
Internal Lab Reference ID
E-031-1999/0
Inventors
Marc Reitman
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A Nurr1-Knockout Mouse Model for Parkinson's Disease and Stem Cell Differentiation
Description:
The researchers have generated Nurr1-knockout mice via genomic locus inactivation using homologous recombination.
Patent Abstract
The researchers have generated Nurr1-knockout mice via genomic locus inactivation using homologous recombination. Transcription factor Nurr1 is an obligatory factor for neurotransmitter dopamine biosynthesis in ventral midbrain. From a neurological and clinical perspective, it suggests an entirely new mechanism for dopamine depletion in a region where dopamine is known to be involved in Parkinson's disease. Activation of Nurr1 may be therapeutically useful for Parkinson's disease patients; therefore, the mice would be useful in Parkinson's disease research. Additionally, Nurr1 has been shown to be critical for development of midbrain dopaminergic neurons, and thus may contribute to stem cell-based therapies for neurological disorders. Nurr1 is also important for osteoblast differentiation, suggesting a general role in stem cell differentiation and growth.
Details
Internal Lab Reference ID
E-024-1999/0
Inventors
Vera Nikodem
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A3 Adenosine Receptor Agonists for Treating Chronic Neuropathic Pain
Description:
The current invention describes selective A3 Adenosine Receptor agonists and their in vivo activity reducing or preventing development of chronic neuropathic pain in an animal model. Chronic neuropathic pain (NP) is a widespread condition that is often associated with diabetes, cancer chemotherapy, injury as well as a variety of other diseases. Current therapies for NP are not always effective and patients suffer from serious side effects, such as liver toxicity and addiction. Opioids, while effective against acute pain, are not the first line of treatment for chronic NP because of their addictive qualities and low efficacy. Thus, there is an unmet need for chronic neuropathic pain treatment that operates on a different mechanism.
Patent Abstract
The current invention describes selective A3 Adenosine Receptor agonists and their in vivo activity reducing or preventing development of chronic neuropathic pain in an animal model. Chronic neuropathic pain (NP) is a widespread condition that is often associated with diabetes, cancer chemotherapy, injury as well as a variety of other diseases. Current therapies for NP are not always effective and patients suffer from serious side effects, such as liver toxicity and addiction. Opioids, while effective against acute pain, are not the first line of treatment for chronic NP because of their addictive qualities and low efficacy. Thus, there is an unmet need for chronic neuropathic pain treatment that operates on a different mechanism.
Benefits
The compounds are consistently highly selective and have smaller molecular weight, thus greater oral bioavailability is possible.
Details
Internal Lab Reference ID
E-742-2013/0
Patent Number
PCT/US2014/066609 US Application No. 15/039,778 US
Inventors
Kenneth Jacobson
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A3 Adenosine Receptor Agonists to Treat Chemotherapy-induced Peripheral Neuropathy
Description:
This invention claims species-independent agonists of A3AR, specifically (N)-methanocarba adenine nucleosides and related pharmaceutical compositions. The A3adenosine receptor (A3AR) subtype has been linked with helping protect the heart from ischemia, controlling inflammation, and regulating cell proliferation. Agonists of the human A3AR subtype have been developed that are also selective for the mouse A3AR while retaining selectivity for the human receptor. This solves a problem for clinical development because animal model testing is important for pre-clinical validation of drug function. Novel agonists have been made that exhibit as much as 6000x selectivity for A3versus A1in humans while retaining at least 400x selectivity for A3versus A1in mice. In addition, the molecules of the invention exhibit very low nanomolar affinity. This innovation will not only facilitate moving A3agonists into the clinical phase of drug development by being more amenable to animal studies, but also provide much greater selectivity in humans, and thereby potentially fewer side effects than drugs currently undergoing clinical trials.
Patent Abstract
This invention claims species-independent agonists of A3AR, specifically (N)-methanocarba adenine nucleosides and related pharmaceutical compositions. The A3adenosine receptor (A3AR) subtype has been linked with helping protect the heart from ischemia, controlling inflammation, and regulating cell proliferation. Agonists of the human A3AR subtype have been developed that are also selective for the mouse A3AR while retaining selectivity for the human receptor. This solves a problem for clinical development because animal model testing is important for pre-clinical validation of drug function. Novel agonists have been made that exhibit as much as 6000x selectivity for A3versus A1in humans while retaining at least 400x selectivity for A3versus A1in mice. In addition, the molecules of the invention exhibit very low nanomolar affinity. This innovation will not only facilitate moving A3agonists into the clinical phase of drug development by being more amenable to animal studies, but also provide much greater selectivity in humans, and thereby potentially fewer side effects than drugs currently undergoing clinical trials.
Benefits
Oral dosing as these A3AR agonists are selective and not associated with cardiac or hemodynamic effects that may result from stimulation of A1or A2A receptors.
Details
Internal Lab Reference ID
E-140-2008/1
Inventors
Kenneth Jacobson
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A3 Adenosine Receptor Agonists to Treat Chemotherapy-induced Peripheral Neuropathy
Description:
This invention claims species-independent agonists of A3AR, specifically (N)-methanocarba adenine nucleosides and related pharmaceutical compositions. The A3adenosine receptor (A3AR) subtype has been linked with helping protect the heart from ischemia, controlling inflammation, and regulating cell proliferation. Agonists of the human A3AR subtype have been developed that are also selective for the mouse A3AR while retaining selectivity for the human receptor. This solves a problem for clinical development because animal model testing is important for pre-clinical validation of drug function. Novel agonists have been made that exhibit as much as 6000x selectivity for A3versus A1in humans while retaining at least 400x selectivity for A3versus A1in mice. In addition, the molecules of the invention exhibit very low nanomolar affinity. This innovation will not only facilitate moving A3agonists into the clinical phase of drug development by being more amenable to animal studies, but also provide much greater selectivity in humans, and thereby potentially fewer side effects than drugs currently undergoing clinical trials.
Patent Abstract
This invention claims species-independent agonists of A3AR, specifically (N)-methanocarba adenine nucleosides and related pharmaceutical compositions. The A3adenosine receptor (A3AR) subtype has been linked with helping protect the heart from ischemia, controlling inflammation, and regulating cell proliferation. Agonists of the human A3AR subtype have been developed that are also selective for the mouse A3AR while retaining selectivity for the human receptor. This solves a problem for clinical development because animal model testing is important for pre-clinical validation of drug function. Novel agonists have been made that exhibit as much as 6000x selectivity for A3versus A1in humans while retaining at least 400x selectivity for A3versus A1in mice. In addition, the molecules of the invention exhibit very low nanomolar affinity. This innovation will not only facilitate moving A3agonists into the clinical phase of drug development by being more amenable to animal studies, but also provide much greater selectivity in humans, and thereby potentially fewer side effects than drugs currently undergoing clinical trials.
Benefits
Oral dosing as these A3AR agonists are selective and not associated with cardiac or hemodynamic effects that may result from stimulation of A1or A2A receptors.
Details
Internal Lab Reference ID
E-140-2008/1
Inventors
Kenneth Jacobson
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Alb-tTA (Tg(Alb1-tTA)3123Lng) Mouse Model for Liver Function Studies
Description:
Tetracycline-responsive transcriptional activator driven by the liver-specific mouse albumin promoter (Alb-tTA). The E. Coli tetracycline operon regulatory system was used to generate a liver-specific transcription activation system that was inhibited by tetracycline. The transcription activator was a fused protein consisting of a tetracycline repressor gene (tetR) that was only active in the presence of tetracycline and a herpes simplex virus protein (VP-16) transcription activating domain. Transcription was induced only in the absence of tetracycline (Tet-Off). A liver-specific promoter such as mouse albumin determined that the tetracycline-regulated transcriptional activator (tTA) would be expressed specifically in liver. To study the effect of the transcription activator on a target gene (for example, Simian Virus 40 (SV4) large tumor (T) antigen (TAg)) specifically in liver, Alb-tTA mice were mated with transgenic mice in which the Target gene (TAg) was controlled by the E.Coli Tetracycline Operator (Tet-O). In this example, TAg was expressed in hepatocytes in the absence of Tetracycline, leading to hepatoma formation. When the mice were treated with tetracycline, TAg was not expressed and hepatomas did not form.
Patent Abstract
Tetracycline-responsive transcriptional activator driven by the liver-specific mouse albumin promoter (Alb-tTA). The E. Coli tetracycline operon regulatory system was used to generate a liver-specific transcription activation system that was inhibited by tetracycline. The transcription activator was a fused protein consisting of a tetracycline repressor gene (tetR) that was only active in the presence of tetracycline and a herpes simplex virus protein (VP-16) transcription activating domain. Transcription was induced only in the absence of tetracycline (Tet-Off). A liver-specific promoter such as mouse albumin determined that the tetracycline-regulated transcriptional activator (tTA) would be expressed specifically in liver. To study the effect of the transcription activator on a target gene (for example, Simian Virus 40 (SV4) large tumor (T) antigen (TAg)) specifically in liver, Alb-tTA mice were mated with transgenic mice in which the Target gene (TAg) was controlled by the E.Coli Tetracycline Operator (Tet-O). In this example, TAg was expressed in hepatocytes in the absence of Tetracycline, leading to hepatoma formation. When the mice were treated with tetracycline, TAg was not expressed and hepatomas did not form.
Details
Internal Lab Reference ID
E-125-2012/0
Inventors
Tsanyang (Jake) Liang
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Antagonist of A3 Adenosine Receptor Fluorescent Probes for the Study of Diseases that Involve A3 Signaling
Description:
This molecular probe may serve as a companion tool to identify and stratify patient populations based on the prevalence of the target A3adenosine receptors.
Patent Abstract
This molecular probe may serve as a companion tool to identify and stratify patient populations based on the prevalence of the target A3adenosine receptors. Small molecule drugs, A3AR-selective agonists, are currently in advanced clinical trials for the treatment of hepatocellular carcinoma, autoimmune inflammatory diseases, such as rheumatoid arthritis, psoriasis, and dry eye disease, and other conditions.
Benefits
Avoids the use of radioisotopes in this part of the R&D process.
Details
Internal Lab Reference ID
E-073-2012/0
Patent Number
13/748,826 (Note: a separate license may be requir
Inventors
Kenneth Jacobson
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Bcl-x LoxP (Bcl2l1 tm1.1Mam) Mouse Model for Developmental Biology Studies
Description:
Floxed Bcl-x: Conditional knockout of pro-survival Bcl-x in primordial germ cells was used to study the balance between pro-apoptotic Bax during embryogenesis.
Patent Abstract
Floxed Bcl-x: Conditional knockout of pro-survival Bcl-x in primordial germ cells was used to study the balance between pro-apoptotic Bax during embryogenesis. Bcl-x is a pro-survival protein that opposes the pro-apoptotic action of Bax which interacts with mitochondria to activate the caspase 9 pathway. Mice in which the Bcl-x gene is inactivated die at E12.5. To be able to study lineage-specific activities of Bcl-x at different stages of development, the Cre-LoxP recombination system was used. Homologous recombination was used to flank the promoter, exon1, and major coding exon2 of the Bcl-x gene with loxP sites. The targeted allele contained a loxP flanked (or floxed) neomycin cassette in the Bcl-x promoter, and an additional loxP site in intron 2. Floxed Bcl-x has been used to study the balance between Bcl-x and Bax in primordial germ cells that undergo controlled levels of cell reduction due to apoptosis, the induction of hemolytic anemia and splenomegaly following conditional deletion of the Bcl-x gene from erythroid cells, the protection of hepatocytes from apoptosis and ensuing fibrotic response by Bcl-x, and the demonstration that Bcl-x is critical for the survival of dendritic cells, important regulators of immune function.
Details
Internal Lab Reference ID
E-115-2012/0
Inventors
Lothar Hennighausen
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Broadly Neutralizing Anti-HIV Monoclonal Antibody That Targets a New Epitope on gp41
Description:
Blocking entry of HIV into cells and vaccine development against HIV are the prime targets of HIV therapy and prevention, respectively. Current invention describes a monoclonal Fab anti-HIV antibody isolated through panning against the chimeric construct NCCG-gp41 by Antibodies-by-Design (Morphosys). One of the antibodies has broadly neutralization ability against several HIV subtypes in an envelope-pseudotyped-virus neutralization assay. This antibody was also shown to have synergistic effect with a gp41-derived peptide discovered in this laboratory in inhibiting HIV-1 fusion.
Patent Abstract
Blocking entry of HIV into cells and vaccine development against HIV are the prime targets of HIV therapy and prevention, respectively. Current invention describes a monoclonal Fab anti-HIV antibody isolated through panning against the chimeric construct NCCG-gp41 by Antibodies-by-Design (Morphosys). One of the antibodies has broadly neutralization ability against several HIV subtypes in an envelope-pseudotyped-virus neutralization assay. This antibody was also shown to have synergistic effect with a gp41-derived peptide discovered in this laboratory in inhibiting HIV-1 fusion.
Benefits
Can be potentially used as a therapeutic agent to block HIV-1 entry into cells.
Details
Internal Lab Reference ID
E-229-2008/0
Inventors
G. Marius Clore
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Facilities
Displaying 1 - 9 of 9
Laboratory of Biochemistry and Genetics
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The Laboratory of Biochemistry and Genetics uses molecular genetics, biochemical techniques, and physical chemical approaches, to study a diverse range of topics related to disease and health. These include: prions (infectious proteins) in yeast; the roles of chaperones and other components in yeast prions; centrosome replication and function; gamete development, meiosis, and fertilization; molecular crowding; biosynthesis of polyamines and their roles in translation and other functions; and bacterial pathogenesis and antibiotic r​esistance in ulcer disease.​​​
Expertise
Our goal is to discover new knowledge useful in understanding basic biology and disease processes. Understanding the mechanisms of yeast infectious diseases, including prions, mechanisms of early development and of centrosome duplication, chaperone action on pathologic aggregates, polyamine action...
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Laboratory of Biological Modeling
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The Laboratory of Biological Modeling is defined by both its methodologies and its areas of application. We use mathematical modeling in many forms and apply it to a diverse array of problems, mostly related to diabetes, obesity, and metabolism.​
Expertise
The laboratory's principal investigators are theorists who are trained in mathematics and physics who apply mathematical modeling to a variety of biological problems. We develop models in concert with experiments carried out either by our fellows or experimental collaborators and validate the...
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Laboratory of Bioorganic Chemistry
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The Laboratory of Bioorganic Chemistry explores problems at the interface of chemistry and biology.
Expertise
Scientists in the lab study diverse topics in bioorganic chemistry. These include: the development of conjugate vaccines from synthetic carbohydrate antigens; the pharmacology of receptors and the discovery of drugs that act as agonists or antagonists of G protein-coupled receptors (GPCRs);...
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Laboratory of Cell and Molecular Biology
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The Laboratory of Cell and Molecular Biology investigates the organization, compartmentalization, and biochemistry of eukaryotic cells and the pathology associated with human disease.
Expertise
The Laboratory uses molecular genetics and biochemical approaches to understand the mechanisms underlying intracellular trafficking of lipids, nuclear proteins, and other factors regulating transcription, replication, and signal transduction. Researchers in the Laboratory also explore the...
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Laboratory of Cellular and Developmental Biology
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The Laboratory of Cellular and Developmental Biology investigates molecular mechanisms that control differentiation and development in a wide range of model organisms to better understand normal biology and provide insight into human disease.​
Expertise
The Laboratory investigates developmentally programmed gene expression, functional genomics, chromatin and epigenetic modifications, particularly as they relate to cellular differentiation and organismal development. These processes regulate gene expression, signal transduction in multi-cellular...
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Laboratory of Chemical Physics
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Current research in the Laboratory of Chemical Physics is primarily concerned with experimental, theoretical, and computational problems in the structure, dynamics, and function of biological macromolecules.​
Expertise
Scientists in the lab study diverse topics in chemical physics. These include: fundamental aspects of the mechanism of protein folding; new techniques and approaches for determining the structure and dynamics of bioactive molecules; the structure and dynamics of proteins, protein-protein complexes...
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Laboratory of Endocrinology and Receptor Biology
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LERB investigates the molecular mechanisms underlying receptor and hormone actions.
Expertise
Research areas include the biology and regulation of seven transmembrane-spanning (G protein-coupled) and nuclear receptors. Scientists in the lab study receptors and hormones related to thyroid function, sensory tissue development, and adipocyte biology at the molecular level. The purpose of our...
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Laboratory of Genetics and Physiology
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The Laboratory of Genetics and Physiology (LGP) explores the biology of cytokines. In particular we investigate genetic and epigenetic mechanisms used to control development of the mammary gland and liver metabolism and cancer.​
Expertise
The emphasis of our research is on theoretical and medical problems related to the role of transcription factors (STAT5) that mediate cytokine action and histone methyltransferases (EZH1 and EZH2). Using traditional and cell-specific gene knock-out mice, researchers in LGP have discovered that...
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Laboratory of Molecular Biology
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The Laboratory of Molecular Biology brings together scientists with a broad range of expertise in biological structure and function. In this environment, geneticists, biochemists, and developmental biologists interact with physical chemists and structural biologists to address problems of mutual interest.
Expertise
Scientists in the lab study diverse topics in biology. These include: structural biology and its relationship to biochemical mechanisms; mechanisms of recombination related to antibody diversity; transposable elements and retroviral integrations; protein stability and quality control; single...
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