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Tumor cell lines are important tools for the study of cancer. However, most tumor cell lines available today do not mimic physiological tumor development, progression, and host immune responses. Autochthonous tumors include spontaneously occurring tumors and chemical, viral, or physical carcinogen-induced tumors. They are considered to model human tumors more closely than transplanted tumors. Autochthonous tumors can be generated de novo in a model organism of interest and are thought to resemble physiological human tumor conditions.

Computer and imaging technologies led to the development of digital pathology and the capture and storage of pathological specimens as digitally formatted images. The use of artificial intelligence (AI) in digital pathology, such as in three-dimensional (3D) reconstruction, requires analyses of high volumes of data. This resulted in increased demands for processing and acquisition of digital images of pathology samples. Increased usage cannot be met by the time-consuming, manual, and laborious methods currently used.

Bioluminescence imaging with luciferin-luciferase pairs is a well-established technique for tracking cells and other biological features in animal models. Bioluminescent is a chemical process which does not require an external input for excitation. Bioluminescent imaging is often limited to monitoring single processes in vivo due to the lack of distinguishable probes. Additionally, existing probes typically operate with light in the visible range, which is highly scattered and exhibits poor tissue penetration. 

Pancreatic cancer is the fourth most common cause of cancer deaths in the U.S. The overall 5-year survival rate is 8.5%. Glypican-1 (GPC1) is a cell surface heparan sulfate proteoglycan protein overexpressed in pancreatic cancer. Due to preferential expression, GPC1 represents a potential candidate for targeted therapy for pancreatic cancer and other GPC1-expressing cancers, such as prostate.

Despite several partially effective prophylactic vaccines for SARS-CoV-2 exist, patients worldwide still succumb to COVID-19. New therapeutics to treat this disease are still needed.  Upon host invasion, a critical step in the pathogenesis of COVID-19 is intracellular replication of SARS-CoV-2 before viral particles invade nearby healthy cells. This triggers an extreme inflammatory response that may lead to acute respiratory distress syndrome (ARDS) or transmission to another host.

Immune checkpoint inhibitors (ICIs) vastly improved the outcome of various advanced cancers; however, many are less likely to respond to single-agent ICI. Tumors with low T-cell infiltration are "immunologically cold" and less likely to respond to single-agent ICI therapy. This diminished response is presumably due to the lack of neoantigens necessary to activate an adaptive immune response. On the other hand, an "immunologically hot" tumor with high T-cell infiltration has an active anti-tumor immune response following ICI treatment.

Nonalcoholic fatty liver disease is caused by several factors including 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), an environmental contaminant. TCDD causes lipid accumulation in humans by inducing the Solute Carrier Family 46 Member 3 (SLC46A3) gene expression. To effectively study TCDD-mediated lipid accumulation, research tools such as SLC46A3 knockout cells and animal models are required.

Programed Death-Ligand 1 (PD-L1, also known as B7-H1 or CD274) is a cell surface protein that binds to Programmed Cell Death Protein 1 (PD-1, also known as CD279). An imbalance in PD-1/PD-L1 activity contributes to cancer immune escape.  PD-1 is expressed on the surface of antigen-stimulated T cells. The interaction between PD-L1 and PD-1 negatively regulates T cell-mediated immune responses. It has been suggested that disrupting the PD-L1/PD-1 signaling pathway can be used to treat cancers. The aberrant expression of PD-L1 on multiple tumor types supports this suggestion.

This technology describes additional methods of using the griffithsin anti-viral polypeptides described in related NCI invention (reference number E-106-2003).  Specifically, this invention describes the use of GRFT to inhibit viral infection of hepatitis C viral infection, a severe acute respiratory syndrome (SARS) viral infection, an H5N1 viral infection, or an Ebola viral infection. 

Three-dimensional (3D) cell cultures systems are important for studying cell biology because they provide in vivo-like microenvironments more physiologically relevant than two-dimensional (2D) culture systems. In 3D culture systems, cells are grown in culture matrixes and turn into spheroids and organoids later processed for downstream analysis by microscopy and histology techniques. The processing of 3D cultures for analysis by microscopy or histology is laborious and time-consuming due to incompatibility of the 3D culture vessels and the microscopy and pathology blocks.