The invention is a cell line (Human embryonic kidney 293) stably expressing a recombinant human cardiac voltage-gated sodium channel (hHl). The cells enable high throughput screening of compounds that modulate sodium channel activity.
This invention relates to methods for identifying peptides and other compounds which block or enhance G protein coupled receptor mediated signaling with high affinity and specificity and/or which stabilize a particular conformer of a G protein coupled receptor. Assays, methods of treatment and other methods developed in conjunction with these methods also are disclosed.
An electrophoresis chamber having the separation capability of a thicker chamber by the addition of a number of ports along the length of the chamber that can act as inlets or outlets. The device introduces cross flow by either a plurality of input and output ports along opposite walls of the chamber or by a tapered chamber having a plurality of output ports. Since the mobility of the particles is lateral to the direction of flow and the cross flow velocity is opposite in direction and greater than the maximum electrophoretic velocity of the particles being separated such particles are carried to the wall of a narrow linear chamber and will pass through ports provided in the wall spaced at strategic distances along the wall separation is achieved. In addition, because the sample and the outlet electrode surface are of like sign there is no deposition of the sample on the electrode surface.
The technology described here permits the delivery of therapeutic or diagnostic (tumor imaging) molecules to a variety of tumor types in a targeted fashion. Current methods for targeting therapeutic agents to tumors have limited utility because they (i) produce toxic effects through reactions with normal tissues; (ii) lack the ability to bind to multiple tumor types and/or (iii) lack tumor specificity. This technology is based upon the fact that certain proteins are upregulated in blood vessels in response to irradiation. These upregulated proteins can act as targets for binding molecules such as antibodies, peptides, or other chemicals. Attaching an anti-tumor therapeutic unit, such as a radioisotope, to one of these binding molecules (e.g. an antibody) provides a way to treat or detect a variety of tumor types and stages while avoiding damage to normal tissue. Licensing Opportunity: A suite of patents and patent applications available for licensing includes compositions of radiation-inducible tumor proteins, and molecules that bind these proteins such as peptides and antibodies; along with methods of using these ligands for treatment and for identification of radiation inducible ligands in tumors. State of development/future plans: Screening a phage display library (murine) has resulted in production of 13 recombinant antibodies that bind to an identified radiation-inducible antigen. Only 2 (designated Lead and Control ScFv) of the 13 recombinant antibodies bound radiation-induced antigen in mice and are depicted in the accompanying figure. Of these two, the LEAD ScFv specifically bound tumor (see figure). Research is moving towards humanizing the lead antibody and identifying the specific epitope bound by the antibody.
Dr. Liang has identified a new protein (termed "Killin") that represents a novel protein for cancer diagnosis, treatment and drug screening. Killin is a small (178 amino acids) nuclear DNA binding protein shown to play a role in cell cycle control.
The present invention is directed to particular human monoclonal antibodies and fragments thereof that find use in the detection, prevention and treatment of respiratory syncytial virus infections. In particular, these antibodies may neutralize RSV. Also disclosed are improved methods for producing monoclonal antibodies.
Scientists at Vanderbilt have developed an entirely plasmid-based system to better utilize reoviruses as a research tool. The system allows for generating a reovirus entirely from cloned cDNAs comprising three steps involving fairly well-known techniques.
This invention provides bioluminescence resonance energy transfer (BRET) system that comprises four parts: 1) a bioluminescent protein that has luciferase activity; 2) an acceptor fluorophore that can accept the energy from the bioluminescent protein when they are associated, in the presence of the appropriate substrate; 3) a modulator that influences the proximity or the orientation of the bioluminescent protein and the fluorophore, and 4) an appropriate substrate to activate the luciferase activity of the bioluminescent protein. The components of this system interact to influence the spatial relationship between the bioluminescent protein and the fluorophore, that is demonstrated by the light emission from the system. The modulator can be a single entity, covalently attached to both the bioluminescent protein and the fluorophore, it can be two separate entities, each linked covalently to either the bioluminescent protein or the fluorophore, or an alternative configuration that falls within the scope of the invention. Thissystem can be used in both in vivo or in vitro assays to detect molecular changes in a wide variety of applications, and is amenable to automation. In particular, it is useful for assaying protein interactions, enzyme activities and the concentration of analytes or signaling molecules in cells or in solution.
Vanderbilt researchers have discovered specific morphogens that can promote differentiation of embryonic stem cells to cardiomyocytes. In addition when these morphogens are added to stem cells during differentiation a 10 to 20 fold increase is seen in cardiomyocyte formation. Thus addition of such morphogens may prove to be a valid therapy for cardiac repair and regeneration.
This is a genetically engineered mouse ES stem cell line marking cardiomyocytes with red fluorescent protein (RFP). These cells have been used in high-throughput screens by Vanderbilt researchers for pro-cardiogenic factors. In addition the construct used in this cell line could be used to mark the cardiac progeny of transplanted stem cells, generate stable human ES cell lines, or engineer iPS for cardiac lineage studies.
Dr. Piston's group has generated a variant of the enhanced cyan fluorescent protein (ECFP) that has improved brightness, more resistance to photo-bleaching and a fluorescence lifetime that is best fit by a single exponential.
Dr. Hawiger and colleagues developed a novel form of cell-penetrating fetal hemoglobin. This technology is useful for the treatment of hemoglobinopathies or to increase oxygen delivery in any condition. The preparation is stable and sterile. Upon reconstitution, the treatment can be delivered I.V. or through transfusion.
The mouse embryonic stem cell line, CGR8, has been genetically modified to express luciferase under the control of either the wnt or the BMP promoter system. This technology allows rapid visualization or genetic modification of wnt and BMP pathways in development.