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.

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.

X-linked nephrogenic diabetes insipidus (XNDI) is a severe kidney disease caused by inactivating mutations in the V2 vasopressin receptor (V2R) gene that result in the loss of renal urine-concentrating ability. At present, no specific pharmacological therapy has been developed for XNDI, primarily due to the lack of suitable animal models. This technology provides a unique and viable animal model of XNDI. NIH investigators have generated mice in which the V2R gene could be conditionally deleted during adulthood by administration of 4-OH-tamoxifen.

This technology includes a system for automatic artifact-free measurement and visualization of tissue strain by MRI at native resolution. The investigation of regional soft tissue mechanical strain can serve as a unique indicator for different related disorders. For example, measurement of myocardial tissue during contraction can help calculate, track, and assess cardiac stress. Currently, methods such as tagging MRI (tMRI) are used for imaging soft tissue deformation. Despite being well validated, methods such as tMRI suffer from low spatial and temporal resolution.

This technology includes a precise measurement assay of cellular FMRP levels in patients, which can assist in the diagnosis and assess the severity of Fragile X syndrome (FXS). FXS is an X-linked disorder that produces intellectual disability, cognitive impairment, epilepsy, depression and anxiety. FXS is caused by mutations in the Fragile X Mental Retardation-1 (FMR1) gene that result in the absence or a loss of function of its protein product, FMRP.

This technology includes five microRNA mimics which were identified to improve the functional expression of hard-to-express membrane protein. These miRNAs are: hsa-miR-22-5p; hsa-miR-18a-5p, hsa-miR-22-3p, hsa-miR-429 and hsa-miR-2110. Improving expression level of recombinant mammalian proteins is vital, as the adequate supply of correctly folded proteins is the prerequisite for all structure and function studies.

This technology includes Cyclopentane-modified Peptide Nucleic Acids (cp-PNAs) which can be combined with (forced-intercalation) FIT-PNAs to create highly sensitive probes that detect the presence of complementary RNA sequences. We have studied the beneficial effects of incorporating cyclopentane groups into the backbone of PNAs, which leads to proper preorganization of the PNA backbone into the conformations needed to bind complementary RNA sequences. The cp-PNAs typically have improved thermodynamic stability for binding to complementary nucleic acids compared to unmodified PNAs.

This technology includes a therapy and companion diagnostic which can be used for the early diagnosis and treatment of sepsis and sepsis-induced acute kidney injury (AKI). Mitochondrial damage plays a key role in sepsis-induced acute kidney injury BAM15 [2-ftuorophenyl){6-[(2- fluorophenyl)am ino]{1 ,2,5-oxadiazolo[3,4-e]pyrazin-5-yl)}amine] is a mitochondrial uncoupler that protects mitochondria with more specificity and less cytotoxicity than other uncouplers. Mitochondrial DNA (mtDNA) is a damage associated molecular pattern that is increased in human sepsis.

This technology includes a semi-automatic and affordable protein purification system that produces purified proteins with yields and purities comparable to an automatic protein purification system for less than 10% of its cost, which can be used for studying protein structure and function, as well as antibody purifications and drug screenings. Additionally, the new system is flexible and customizable for use with both custom-made and commercial pre-made resin columns with either gravity flow or low-pressure configurations.