Isotopes of Alpha Ketoglutarate and Related Compounds for Hyperpolarized MRI Imaging

This technology includes 1-13C-ketoglutarate which can be used for imaging the conversion to hydroxyglutarate (HG) or Gln in cancer cells with an IDH1 mutations by hyperpolarized MRI. The ability to detect the status of IDH1 mutations is clinically prognostic for multiple cancers. These exciting observations are limited by two factors, the major one being that the natural abundance of 13C at position C5 overlaps with 1-13C-2-hydroxyglutarate peak, which limits the sensitivity of analysis and prevents simultaneous observations of HG and Gln formation.

Human Monoclonal Antibodies to Generate Chimeric Antigen Receptor (CAR) T-cells to Treat Patients with Advanced Clear Cell Renal Cell Carcinoma (ccRCC).

This technology includes six human monoclonal antibodies (mAbs) that target tumor antigens derived from the CT-RCC HERV-E (human endogenous retrovirus type E) to generate Chimeric Antigen Receptor (CAR) T cells to treat patients with advanced clear cell renal cell carcinoma (ccRCC). These mAbs were identified from Adagene Inc’s human antibody phage library, and data show that majority of these mAbs only bind to CT-RCC HERV-E+ ccRCC cells, which express TM but not CT-RCC HERV-E non-expressing ccRCC cells nor non-RCC cells.

High Relaxivity Mulitivalent Gadolinium on a Peptide Scaffold for Targeted MRI Applications in Disease Diagnosis

This technology includes a peptide containing alternating Alanine and Lys(DOTA-Gd) residues can be used to increase the MRI relaxivity of a peptide. The low molecular weight construct can be appended to proteins, antibodies and peptides to increase MRI signals. This approach offers advantages over previous dendrimeric constructs.

Single cell profiling of chromatin Occupancy and RNAs Sequencing (scPCOR-seq)

Cell-to-cell heterogeneity in gene expression is a widespread phenomenon, and may play important roles in cellular differentiation, function and disease development. Human Cell Atlas aims to profile gene expression in every single human cells. Recent studies have implicated a potential role of chromatin in the heterogeneity in gene expression. Understanding the mechanisms of cellular heterogeneity requires simultaneous measurement of RNA and occupancy of histone modifications and transcription factors on chromatin due to their critical roles in transcriptional regulation.

Intralipid as a Contrast Agent to Enhance Subsurface Blood Flow Imaging

This technology includes a blood flow imaging method that allows for a higher density of smaller particles to be detected. Current imaging methods that are based on Doppler measurements are limited by the discontinuity in the capillary flow in the space between red blood cells. The core technology is to use a scattering agent to enhance capillary flow or microcirculation. This technology has been tested for optical coherence Doppler tomography, but can be expended to any Doppler based flow imaging techniques such as laser speckle imaging.

Radiotherapy and Imaging Agent-based on Peptide Conjugated to Novel Evans Blue Derivatives with Long Half-life and High Accumulation in Target Tissue

This technology includes a newly designed, truncated Evans Blue (EB) form which allows labeling with metal isotopes for nuclear imaging and radiotherapy. Unlike previous designs, this new form of truncated EB confers site specific mono-labeling of desired molecules. The newly designed truncated EB form can be conjugated to various molecules including small molecules, peptides, proteins and aptamers to improve blood half-life and tumor uptake, and confer better imaging, therapy and radiotherapy.

A Novel Therapy/Companion Diagnostic (BAM15 And mtDNA) for Sepsis and Sepsis-induced Acute Kidney Injury

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.

Modulating Autophagy as a Treatment for Lysosomal Storage Diseases

Researchers at NIAMS have developed a technology for treatment of lysosomal storage diseases by inhibition of autophagy. Pompe disease is an example of a genetic lysosomal storage disease caused by a reduction or absence of acid alpha-glucosidase (GAA). Patients with Pompe disease have a lysosomal buildup of glycogen in cardiac and skeletal muscle cells and severe cardiomyopathy and skeletal muscle myopathy. Treatment of Pompe disease by GAA enzyme replacement therapy is quite ineffective for the skeletal muscle myopathy.

Identification of a Novel Parvovirus for Vaccine Development and Use as a Diagnostic Tool

This technology includes a procedure for novel virus identification in a variety of human specimens by solexa high-throughput sequencing, which allows for the screening a large number of clinical specimens for novel virus discovery in a highly efficient and relatively economical method. By using this technique, we have successfully identified a novel parvovirus from samples of seronegative hepatitis patients.

Engineered Human Induced Pluripotent Stell Cell (iPSC) Lines for Multiple Therapeutic and Diagnostic Uses

This technology includes ten engineered human induced pluripotent stem cell (iPSC) lines with reported genes inserted into safe harbor sites for use in therapy and diagnostic screening assay development as well as basic stem cell biology research. These cell lines have the potential to differentiate into all cells in the body, and theoretically can proliferate/self-renew indefinitely.

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