The overall objective is to purify a novel tumor necrosis factor (tnf)-inhibiting peptide (tnfi) and analyze its potential therapeutic value. the phase i objective is to purify and determine the amino acid sequence of tnfi. culture supernatants harvested from a transformed cell line will be… More

The research is designed to test the feasibility and limits of a novel method developed for theselection of desired biological activities in vivo from random peptide libraries. the method will be adapted for the selection of peptide inhibitors of the hiv-1 protease. the utility of selected… More

Hiv infected macrophages release elevated quantities of il1 and a novel 7kd monokine with pleiotropic activities. on the one hand, it inhibits il1 and il6 induced t lymphocyte comitogenesis, but on the other hand, it stimulates b cell mitogenesis. this immunomodulatory monokine is called janusine… More

K31 is a promising murine anti-CD48 monoclonal antibody (MAB) which can deplete tissue grafts of antigen presenting accessory cells to reduce their immunogenicity. Because any in vivo use of this MAB will be limited by the human anti-mouse antibody (HAMA) response, the overall goal is to use PCR… More

Therapeutic options for hepatocellular carcinoma (HCC) are limited and the results of therapy are dismal. Previous work from this laboratory demonstrated that cationic liposomes can deliver indicator transgenes to liver and lymphoid cells in vivo. We will apply these techniques to HGG by delivering… More

Cancer chemotherapy is limited by toxicity sustained by normal tissues. To increase specificity of drug delivery, antineoplastic agents have been linked to monoclonal antibodies (MABs) that bind to antigens selectively expressed on tumor cells. However, this strategy suffers from several drawbacks.… More

Optimal therapy to prevent graft rejection should be based on the induction of specific tolerance to the donor tissue. Current concepts on immunological tolerance hold that anergy is the result of intercellular signalling after TCR/MHC-peptide interaction in the absence of a so- called Costimulatory… More

Therapeutic options for hepatocellular carcinoma (HCC) are limited, and the results of therapy are dismal. Previous work from this laboratory demonstrated that cationic liposomes can deliver indicator transgenes to liver and lymphoid cells in vivo. We will apply these techniques to HCC by delivering… More

Hepatokines are autocrine or paracrine growth factors for liver tissue. The hepatopoietin described is a novel hepatocyte-specific growth factor. In preliminary work, hepatopoietin was purified to homogeneity (based on SDS-PAGE, reverse phase HPLC and capillary electrophoresis) and found to have a… More

The overall goal of this project is to construct a single chain antibody (sc-ab) expression library. degenerate pcr primers will be used to amplify antibody heavy and light chain variable regions. heavy and light chains will be recombined in vitro using pcr and linked witha 42 bp spacer arm to make… More

Antigen specific selection of antibodies (or other proteins) expressed on the surface offilamentous phage has previously been performed by affinity enrichment on columns or by panning. Avaluable addition to this methodology would be to link receptor-ligand binding in a manner similar toclonal… More

Gram negative bacterial infections continue to account for significant mortality and morbiditydue the inability of new antibiotics to neutralize the deleterious effects of lipopolysaccharide (LPS)released from the bacterial cell surface. LPS initiates an immunoinflammatory cascade characterized… More

Currently there are a variety of in vitro screening assays used to test environmental compoundsand potential drugs for mutagenic and carcinogenic activity. However, these assays generally do notdetect tumor promoters, thus economical screens for these agents are urgently needed. This applicationwill… More

The expression of many inducible genes is regulated at the level of mRNA transcription. Thepromoter regions of these genes are comprised of regulatory sequences that bind a specific combinationof transcription factors. Our aim is to identify and clone novel transcription factors specific… More

The HER2 (c-erbB-2) proto-oncogene is over-expressed in approximately 30% of the>160,000/yr new cases of breast and ovarian cancer, and correlates inversely with prognosis. Whileanti-erbB-2 antibodies and immunoconjugates show much promise for breast cancer therapy, a fullyhuman high-affinity… More

Approximately 40% of patients suffering from the sepsis syndrome are infected with Gram negative bacteria. It is this subset of patients that stand to benefit from new therapies designed to neutralize endotoxin such as anti-lipid A monoclonal antibodies (e. g. E5 or HA-1A) and bacterial permeability… More

Published data suggests that reduced serum tyrosine and phenylalanine concentrations reduce the number of metastasis in various animal cancer models as well as human patients. the longterm goal of this work is to clone, express and evaluate therapeutic enzymes that catabolize one or both of these… More

Activation of both the complement and the contact systems of intrinsic coagulation are implicated ipathophysiology of sepsis. C1-inhibitor (C1-INH) is a member of the superfamily of serine protease ithe major inhibitor of both factor XIIa and kallikrein of the contact system and also the only… More

Deregulation of the bcl-2 oncogene underpins both the etiology and the chemoresistance of many signtumors. The Bcl-2 protein mediates these effects by blocking physiological (programmed) cell death (malignant cells. In vitro models indicate that inhibitors of bcl-2 gene expression block this… More

Our research is based on the report that certain monoclonal antibodies that recognize a 185kDa surfantigen present on the cariogenic bacterium, Streptococcus mutants, when applied to human teeth, aftprofessional cleaning and chlorhexidine treatment, prevent recolonization of the mouth by S.… More

Cryptosporidium parvum is a major cause of diarrhea disease among immunocompromised AIDS patients wlimited treatment options. The overall goal of the present proposal is to develop therapeutic plantiassociated diarrhea diseases. This approach will provide a novel and inexpensive means to prevent… More

Improved methods for the identification of physiologically important protein-protein interactions ademand. We Have devised a novel system which allows the selection of protein or peptide ligands of afrom complex mixtures by virtue of their ability to facilitate the replication of their own genes.… More

Not Available SY Technology, Inc. proposes to develop a smart camera to automatically identify regions of interest (ROI) in imagery. The camera has two target recognition applications. First, to process a correlation surface (obtained by correlating an image with a filter) to identify, enhance and… More

Not Available ISC will develop a miniaturized uncooled thermal imaging sighting system for handheld weapons, including the MP5, M-4, Sig-Sauer P226, and the Beretta 9mm semi-automatic pistol, that not affect the accuracy or the operation of the weapon. This system will include a totally passive… More

Not Available Polarization imaging holds promise for providing significant improvements in contrast in a number of target detection and discrimination applications. It has been demonstrated that manmade objects have a significantly stronger polarization signal than natural backgrounds. There is… More

Not Available There is an increasing desire in many organizations, including the Department of Defense, NASA, and commercial satellite operators, to use constellations or fleets of autonomous spacecraft working together to accomplish complex mission objectives. Multiple satellite systems are… More

Not Available The Kinetic Kill Vehicle Hardware In the Loop Simulation (KHILS) facility requires a Visible Wavelength Scene Projection system for HIL testing of visible sensors. The Visible Projector must meet stressing performance requirements in order to provide valid and credible test results on… More

Not Available This research will develop principles and plans for a user-focused architecture for embedded applications for war fighters. The concept of a user-focused architecture is based on new, sophisticated system services centered in the user interface. These services will allow the user to… More

DESCRIPTION (applicant's abstract): The Achilles heel of most current high-throughput screening (HTS) strategies is the inherent inefficiencies of the available screening assay platforms, leading to excessive rates of false positive and false negative selection. To… More

The emergence of antibiotic-resistant Staphylococcus aureus has created an urgent need for new therapeutic approaches to treat the variety of diseases caused by this common pathogen. S. aureus damages host tissues by the secretion of a variety of toxic exomolecules known as virulence factors. The… More

The common cold is generally not life threatening to most people, but does cause significant morbidity and loss of productivity. For some, particularly those with asthma or who are immunocompromised, it can be quite serious. Prospects are in hand for development of a new therapeutic that could have… More

The common cold is generally not life threatening to most people, but does cause significant morbidity and loss of productivity. For some, particularly those with asthma or who are immunocompromised, it can be quite serious. Prospects are in hand for development of a new therapeutic that could have… More

The emergence of antibiotic-resistant Staphylococcus aureus has created an urgent need for new therapeutic approaches to treat the variety of diseases caused by this common pathogen. S. aureus damages host tissues by the secretion of a variety of toxic exomolecules known as virulence factors. The… More

DESCRIPTION (provided by applicant): The present application is based on the remarkable finding that non-calorigenic thyroid hormones mediate tumor cell apoptosis. A selected lead compound has been identified and shown to interact with microtubules. This compound, DIME, is… More

DESCRIPTION: Eosinophils play a central role in the pathogenesis of allergic diseases. The present application is based on the remarkable finding that sulochrin, a metabolite of Aspergillus, can specifically inhibit eosinophil effector function. The overall goal of this… More

DESCRIPTION (provided by the applicant): The plaques characteristic of Alzheimer?s disease result in part from the abnormal deposition of the peptide beta-amyloid (Abeta). Recent work of Schenk et al. (1999) using a transgenic mouse model of Abeta deposition demonstrated the remarkable capacity… More

DESCRIPTION (Provided by applicant): The opportunistic human pathogen P. aeruginosa utilizes N-acylhomoserine lactones as quorum sensing "autoinducers" to specifically induce numerous virulence genes. AiiA is the first enzyme known to inactivate N-acylhomoserine lactones. Expression of AiiA in… More

DESCRIPTION (provided by applicant): The overall goal of this project is to develop a novel therapy for neurological injury. The concept is to combine two mechanisms known to provide neuroprotection from ischemic damage. Thus, we will combine a nitrone, known to have potent free radical scavenging… More

DESCRIPTION (provided by applicant): The 18-kD cationic protein CAP18 is an antimicrobial protein first isolated from rabbit granulocytes that binds lipopolysaccharide and inhibits many of its biological activities (Larrick et al., 1995). The most active approximately 30 amino acid fragment of… More

DESCRIPTION (provided by applicant): Recently, tumor cells have been found to selectively accumulate certain n-3 fatty acids such as cis-4,7,10,13,16,19-docosahexenoic acid (DHA). DHA-paclitaxel, a conjugate of DHA and paclitaxel, has greatly increased therapeutic efficacy and reduced side effects… More

DESCRIPTION (provided by applicant): Des-asp angiotensin 1 (DAA-1) is a potent endogenous cardiovasculo-protective peptide generated from angiotensin 1 by a novel aminopeptidase. DAA-1 given both iv and po has sub-micromolar protective activity in a number of cardiac and renal pathophysiology. These… More

DESCRIPTION (provided by applicant): Hepatocyte growth factor (HGF) and its receptor, c-Met, are known to play an important role in tumor growth, metastasis and angiogenesis. Met is widely expressed on various types of tumor cells. Thus, an antagonist molecule that blocks the HGF-Met interaction is… More

DESCRIPTION (provided by applicant): The post-genomics era will demand high throughput technologies to generate and evolve proteins and protein-binding molecules. The overall goal of this work is to develop a novel ribo-display technology for in vitro molecular evolution. Preliminary work provides… More

DESCRIPTION (provided by the applicant): Intravenous gamma globulin (IVIG) is a remarkably safe and effective therapy for a number of autoimmune diseases. Recent studies indicate that the binding of Ig Fc to the neonatal Fc receptor determines the half-life of antibodies in vivo. In addition, the… More

DESCRIPTION (provided by applicant): Hepatokines are hepatocyte-derived autocrine or paracrine growth and survival factors. Preliminary data described below demonstrates the identification of a novel hepatokine (HK-1) originally isolated from fetal hepatocytes and patented by this laboratory. The… More

DESCRIPTION (provided by applicant): Recent clinical results with angiogenesis-inhibiting biopharmaceuticals have validated this class of therapeutics as important anti-cancer agents. The most promising therapeutic candidates to date interfere with proangiogenic stimulation by VEGF. Our… More

DESCRIPTION (provided by applicant): The opportunistic human pathogen, Pseudomonas aeruginosa, utilizes acyl-homoserine lactones (acyI-HSL) as quorum sensing autoinducers to activate the expression of numerous virulence genes. Some virulence factors are directly toxic to host tissues while others… More

DESCRIPTION (provided by applicant): Hepatocellular carcinoma (HCC) is one the most common forms of cancer worldwide, with approximately 1,000,000 new cases and 1,300,000 deaths reported annually. It is one of the most lethal forms of cancer, in part due to the fact that HCC cells are highly… More

DESCRIPTION (provided by applicant): The overall goal of this work is to develop a novel monoclonal antibody for cancer therapy. HGF is a paracrine angiogenic factor and an autocrine growth factor for many different types of cancer cells. Thus antagonistic monoclonal antibodies to HGF are expected… More

DESCRIPTION (provided by applicant): Recently, tumor cells have been found to selectively accumulate certain n-3 fatty acids such as cis-4,7,10,13,16,19-docosahexenoic acid (DHA). DHA-paclitaxel, a conjugate of DHA and paclitaxel, has a greatly increased therapeutic efficacy and reduced side… More

DESCRIPTION (provided by applicant): The ultimate goal of this technology development program is improve the detection and quantitation of specific microbes in biological fluids such as blood, cerebrospinal fluid and urine. This technology is based upon a novel enzymatic amplification system called… More

DESCRIPTION (provided by applicant): Published data indicates that bone marrow-derived stem cells injected directly into injured myocardium provides improvement in left ventricular function post-myocardial infarction. Our collaborator, Dr. Randy Lee at UCSF, has developed an alternative proprietary… More

DESCRIPTION (provided by applicant): CF is an autosomal recessive genetic disorder affecting approximately 30,000 patients in the United States and 60,000 patients worldwide, with an average life expectancy of about 30 years. Lung infection with Pseudomonas aeruginosa is a leading cause of… More

DESCRIPTION (provided by applicant): Hepatocellular carcinoma (HCC) is among the world's most common and lethal malignancies with no effective therapy. Because of the normal function of the liver to detoxify xenobiotics, cancers of this tissue are notoriously resistant to chemotherapy. Furthermore,… More

DESCRIPTION (provided by applicant): Neuroblastoma is the most common extracranial solid tumor of childhood. Aggressive chemotherapy and surgery have improved remission rates for young patients, but not for adolescents or adults, in whom neuroblastoma is especially resistant to chemotherapy. Thus,… More

DESCRIPTION (provided by applicant): Obesity is a growing major medical problem worldwide. It is the second most important cause of preventable death in the US, exceeded only by cigarette smoking. Current treatments consist of diet, exercise, behavior modification, surgical intervention, and… More

DESCRIPTION (provided by applicant): The use of antibodies as therapeutic agents has gained increasing acceptance over the last several years, and there are currently 18 FDA-approved monoclonal antibody therapies. The main advantages of antibody-based therapy over traditional, small molecule… More

DESCRIPTION (provided by applicant): The overall objective of this application is to perform necessary studies in preparation for conducting clinical trials in cancer of an immunoadhesin that neutralizes hepatocyte growth factor (HGF). Previously, a Met-Fc immunoadhesion was developed that inhibits… More

DESCRIPTION (provided by applicant): Primary liver cancer, hepatocellular carcinoma (HCC) is one of the most common forms of cancer worldwide, causing an estimated 1.3M deaths annually (Venook, 1994). Because HCC is often detected only in late stages, it is one of the most lethal forms of cancer,… More

DESCRIPTION (provided by applicant): Recent investigations demonstrate the importance of receptor for advanced glycation end products (RAGE) mediated signal transduction in promoting pathogenic inflammation, renal failure and diabetic complications. Animal studies indicate that the extracellular… More

DESCRIPTION (provided by applicant): Congenital obstructive nephropathy is the most frequent cause of renal failure in infants and children, and if left untreated can cause severe renal failure and death. Challenges in the evaluation and management include the lack of clear indications if and when… More

DESCRIPTION (provided by applicant): Severe sepsis is the leading cause of death in intensive care units and accounts for 9.3% of overall deaths in the United States annually (Angus, 2001). This complex disorder is difficult to diagnose and treat, and ther e is a great need for a test that can… More

DESCRIPTION (provided by applicant): Enhanced engraftment of stem cells. There is an urgent need for methods to improve the engraftment efficiency of autologous and allogeneic hematopoietic stem cells (HSC) after myeloablative therapy. Although mobilized p eripheral blood and umbilical cord blood… More

DESCRIPTION (provided by applicant): Novel Bispecific Antibodies Bispecific antibodies (BiAb) are a promising class of protein pharmaceuticals utilized to target and/or redirect therapeutic cells. Numerous BiAbs are under development to direct activated T cells to tumors. Our laboratory (Lee, 2006)… More

DESCRIPTION (provided by applicant): Proteolytic antibodies ( Proteo-abzymes ) are a novel therapeutic modality that has the potential to revolutionize antibody-based therapeutics. The overall goal of this project is to develop potent proteolytic anti-amph iregulin (AR) human monoclonal antibodies… More

DESCRIPTION (provided by applicant): Ulcerative colitis (UC) is a chronic tissue-destructive disease in which cellular inflammation and inflammatory cytokines ultimately lead to damage of the colonic mucosa. There is no effective cure, and while standard t herapies can ameliorate symptoms in some… More

DESCRIPTION (provided by applicant): There is an urgent need for improved therapies for acute and chronic myocardial ischemia. Bone marrow-derived stem cells (SC) injected into acutely injured as well as chronically ischemic myocardium improve left ventric ular function. However, a major limitation… More

DESCRIPTION (provided by applicant): Kinetic Assembly of Bispecific Antibodies Bispecific antibodies (BiAb) are a promising class of protein pharmaceuticals utilized to target and/or redirect therapeutic cells as well as overcome regulatory hurdles for th erapies affecting two targets. Numerous… More

DESCRIPTION (provided by applicant): Recent investigations demonstrate the importance of receptor for advanced glycation end products (RAGE) mediated signal transduction in promoting pathogenic inflammation, renal failure and diabetic complications. Anima l studies indicate that the extracellular… More

DESCRIPTION (provided by applicant): ABSTRACT: A significant need exists to address complications associated with the growing pandemic of diabetes mellitus and metabolic syndrome now estimated to affect gt20 million people in the United States (~7% of the population ). Impaired wound repair, a… More

DESCRIPTION (provided by applicant): Breast cancer is the most frequently diagnosed cancer in the US with an estimated 211,240 new cases of invasive breast cancer and 58,490 new cases of in situ breast cancer in 2005. The mortality rate of 2.3% per year tr anslates into more than 40,000 deaths of… More

DESCRIPTION (provided by applicant): Prostate cancer is the most common malignancy and second-leading cause of cancer deaths among males in the United States, accounting for 1/3 of all new cancers in males with an estimated 232,090 new cases yearly (Jemal, 2005). The mainstay of prostate cancer… More

DESCRIPTION (provided by applicant): Pemphigus vulgaris (PV) is a chronic autoimmune disease targeting skin and mucous membranes, characterized by intraepithelial aphlegmasic flaccid blisters and erosions. It is caused by pathogenic autoantibodies that in duce the separation of keratinocytes (KC)… More

DESCRIPTION (provided by applicant): Alzheimer's disease (AD), the most common form of dementia, is a complex disorder that is difficult to diagnose and treat. Currently, there is no readily available biomarker test panel to aid diagnosis or monitor disea se progression. Although analysis of… More

DESCRIPTION (provided by applicant): An urgent need exists to develop novel therapies for cardiac failure. The Na+/K+ ATPase (NKA) catalyzes active transport of Na+ and K+ ions across the cardiomyocyte plasma membrane. Cardiac glycosides are thought to ha ve a positive inotropic effect by… More

DESCRIPTION (provided by applicant): Tissue Repair During Acute Phase of Myocardial Infarction Cardiovascular disease is the leading cause of mortality and morbidity in developed countries. Each year, over 19 million incidents of sudden cardiac events occu r worldwide, with approximately 1 million… More

DESCRIPTION (provided by applicant): Hepatocyte growth factor (HGF) is a pleiotropic cytokine that promotes cell proliferation, motility, survival, and morphogenesis. HGF binds to its receptor c-Met tyrosine kinase and triggers signal transduction that pro tects cells against apoptosis and enhances… More

DESCRIPTION (provided by applicant): Ulcerative colitis (UC) is a chronic tissue-destructive disease in which cellular inflammation and inflammatory cytokines ultimately lead to damage of the colonic mucosa. There is no effective cure, and while standard therapies can ameliorate symptoms in some… More

DESCRIPTION (provided by applicant): Improved therapy for AMD Age-related macular degeneration (AMD) is a leading cause of visual loss (http://www.nei.nih.gov/eyedata/pbd4.asp) affecting more than 1.75 million people in the USA. Vascular endothelial growt h factor (VEGF) is a major driver of… More

DESCRIPTION (provided by applicant): A Novel Regenerative Therapy for Myocardial Infarction Myocardial infarction (MI) is an acute public health problem killing one third of the 1.5 million Americans afflicted annually. Almost all MIs are caused by ruptureof coronary atherosclerotic plaques with… More

DESCRIPTION (provided by applicant): Monobody for Renal Inflammation End stage renal disease (ESRD) affects gt485,000 Americans, including over 341,000 hemodialysis patients with an estimated 90,000 new cases per year. The annual cost of treating Americanssuffering from some form of kidney failure… More

Cellulose is the most abundant biopolymer on earth. Photosynthesis produces biomass containing over a trillion tons of cellulose annually. This almost inexhaustible source of building blocks for biofuels, bioplastics, and other biochemicals, is key to a renewable, non-petroleum-based chemicals… More

DESCRIPTION (provided by applicant): The goal of this proposal is to develop a novel hybrid bifunctional cytokine ( fusokine ) to promote immune reconstitution and inhibit graft-versus-host disease (GVHD) in cancer patients undergoing hematopoietic stemcell transplantation. The fusokine, termed… More

DESCRIPTION (provided by applicant): The targets of most therapeutic antibodies are found on healthy cells which limits the development of truly tumor-specific therapies and results in a narrow therapeutic index. Using state-of-the-art proteomic and geneprofiling methods, our collaborators have… More

DESCRIPTION (provided by applicant): Disialoganglioside GD2+ tumors account for ~10% of cancer deaths. Anti-GD2 antibody therapies have shown promise in advanced clinical trials in melanoma, neuroblastoma, and other tumors. However, current antibody approaches suffer from significant neurotoxicity… More

DESCRIPTION (provided by applicant): Preeclampsia (PE) is a serious complication of pregnancy manifested by high blood pressure, proteinuria, and edema, sometimes with encephalopathy, seizures, and hepatic failure. PE complicates from 5 to 10% of pregnancies, and is a major cause of maternal and… More