A Mouse Model for Systemic Inflammation in Glucocerebrosidase-Deficient Mice with Minimal Glucosylceramide Storage

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.

A Mouse Model for Type 2 Diabetes

Diabetes affects over 120 million people worldwide (16 million in the US) and is a major health problem with associated health costs estimated at almost $100 billion dollars. Type 2 diabetes affects as many as 10% of the population of the Western World (with 15 million patients in the US alone) and arises from a heterogeneous etiology, with secondary effects from environmental influences. Risk factors for type 2 diabetes include obesity, high blood pressure, high triglycerides and age.

Regulation of RNA Stability

This invention relates to the discovery that tristetraprolin (TTP) can promote the poly(A)RNase (PARN) mediated deadenylation of polyadenylated substrates containing AU-rich elements (AREs). As one aspect of the invention, the inventors have developed a cell free system that may be used for the purposes of assessing the effects of the various system components or their derivatives (i.e. AREs, PARN, or TTP) on the deadenylation process or the effects of various test agents on the deadenylation process.

Interleukin 24 (IL-24) to treat inflammatory diseases

Proinflammatory T-helper 17 cells (Th17) play important roles in host immune defense against infection, but uncontrolled activation of these cells, known as the Th17 response, may cause autoimmune and autoinflammatory diseases (uveitis, multiple sclerosis, rheumatoid arthritis, and Crohn’s disease) through the effects of Th17 lineage cytokines (such as, IL-17F, IL-22 and GM-CSF). Importantly, IL-17A (a proinflammatory cytokine) represses other Th17 lineage cytokines by upregulating the regulatory cytokine IL-24.

Efficacious Fluorinated Cytidine Analog Cancer Therapeutic With Low Toxicity In Animal Studies

Cytidine analogs remain an area of active drug discovery and development, with five FDA approved drugs for the treatment of acute myeloid leukemia (AML). Two of these drugs, azacitidine (Vidaza®) and decitabine (Dacogen®), which were approved for myelodysplastic syndromes in 2004 and 2006, respectively, inhibit the DNA maintenance methyltransferase DNMT1. Because of the general toxicity of azacitidines, other nucleoside analogs are favored as therapeutics.

T Cell Receptors Targeting p53 Mutations for Cancer Immunotherapy and Adoptive Cell Therapy

The tumor protein p53 is a cell cycle regulator. It responds to DNA damage by triggering the DNA repair pathway and allowing cell division to occur or inducing cell growth arrest, cellular senescence, and/or apoptosis. p53 therefore acts as a tumor suppressor by preventing uncontrolled cell division. However, mutations in p53 that impair its cell cycle regulatory functions can induce uncontrolled cell division leading to cancer.

Methods of Producing Thymic Emigrants from Induced Pluripotent Stem Cells

Hematopoietic and pluripotent stem cells can be differentiated into T cells with potential clinical utility. Current approaches for in vitro T cell production rely on Notch signaling and artificial mimicry of thymic selection. However, these approaches result in unconventional or phenotypically aberrant T cells; which may lead to unpredictable behavior in clinical use. Thus, there exists a need for improved methods of generating conventional T cells in vitro from stem cells.
 

Self-Assembling Nanoparticles Composed of Transmembrane Peptides and Their Application for Specific Intra-Tumor Delivery of Anti-Cancer Drugs

Peptides corresponding to transmembrane domains of a number of integral proteins were discovered to spontaneously self-assemble in aqueous solutions into stable and remarkably uniform nanoparticles.  Researchers at the NCI’s Cancer and Inflammation Program have developed fully synthetic, peptide-based, virus-like nanoparticles capable of delivering cytotoxic, radioactive, and imaging agents. 

Structure and function of tumor-target self-assembling particles:

An Anti-Viral Polypeptide: Griffithsin

Virus entry into a susceptible host cell is the first step in the formation of all viral diseases. Controlling viral infections by disrupting viral entry is advantageous for antibody-mediated neutralization by the host’s immune system and as a preventive and therapeutic antiviral strategy. Plant-derived carbohydrate-binding proteins (lectins) have emerged as a new class of antiviral biologics by taking advantage of a unique glycosylation pattern only found on the surface of viruses.

Therapeutic Management of Menkes Disease and Related Copper Transport Disorders

The only currently available treatment for Menkes disease, subcutaneous copper histidinate injections, is successful only in patients with ATP7A gene mutations that do not completely corrupt ATP7A copper transport function (estimated 20-25% of affected patients) and when started at a very early age (first month of life). The combination of viral gene therapy with copper injections provides working copies of the ATP7A copper transporter into the brain, together with a source of the substrate (copper)  needed for proper brain growth and clinical neurodevelopment.

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