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A Transposon Vector From Aedes Aegypti For Use In Vertebrate And Invertebrate Gene Transfer

Background: Therapeutic delivery of genes is a rapidly evolving technique used to treat or prevent a disease at the root of the problem. Another widely used variation of this technique is to insert a transgene into animals and crops for production of desirable proteins. The global transgenic market is currently $24B with annual growth projections of 10%.  Brief Description: UCR Researchers have identified a novel transposon from Aedes aegypti mosquitoes. This mobile DNA sequence can insert itself into various functional genes to either cause or reverse mutations. They have successfully developed a transposon vector system that can be used in both unicellular & multicellular organisms, which can offer notable insight to enhance current transgenic technologies as well as methods of gene therapy.

Isolation of Hepatocytes with High Regenerative Capacity for Repair of Liver Injuries

Hepatocyte diversity has long been known, yet it remains difficult to analyze the distinct properties of the various hepatocyte populations under physiological conditions. A unique subpopulation of periportal hepatocytes were recently identified by UC San Diego researchers. These cells are located in the limiting plate and express Sox9 and HNF4alpha, a hepatocyte transcription factor. The cells were termed HypHP (hybrid hepatocytes) and are a hybrid between a hepatocyte and a duct cell. Transcriptomic and immunohistochemical analyses show expression of hepatocyte-specific genes as well as a small number of genes that are preferentially expressed in bile duct cells. In the unchallenged liver, HypHP are quiescent for at least 9 months after birth, but during chronic liver damage they proliferate and serve as a source of new hepatocytes that repopulate the liver. Chronic liver disease remains the leading cause of liver transplantation, an expensive procedure which is a cause of morbidity and mortality. Others have suggested cell transplantation, such as stem cells, as an alternative. However, suitable matches are difficult to find. Hepatocytes can be derived from induced Pluripotent Stem Cells (iPSCs), however, this procedure does not generate fully functioning hepatocytes. Other approaches for cell transplantation use ductal cells, which also does not generate fully functional cells.

A Method To Modulate The Pathologic Multireceptor Signaling Via The Giv-Gi Axis In Diverse Diseases / 2015-082

Most common diseases, e.g., cancer, inflammation, diabetes are driven by multiple cell surface receptors that trigger and sustain a pathologic signaling network. The largest fraction of therapeutic agents that target individual receptors/pathways often eventually fail due to the emergence of compensatory mechanisms. Recently, UCSD researchers identified GIV protein as a central platform for receptor cross-talk which integrates signals downstream of a myriad of upstream receptors, and modulates several key pathways within downstream signaling network, all via activation of trimeric G proteins. The researchers have conducted proof-of-concept studies demonstrating that non-genetic exogenous modulation of the GIV-Gi signaling interface using cell-penetrable synthetic GIV-derived peptides is an effective strategy to reset pathologic signaling networks downstream multiple receptors in a diverse array of pathophysiologic conditions.

Biomarkers For Assessment Of Subtypes Of Non-Alcoholic Fatty Liver Disease

Non-Alcoholic Fatty Liver Disease (NAFLD) is the most common form of chronic liver disease and comprises conditions ranging from steatosis, non-alcoholic steatohepatitis (NASH) and cirrhosis. About 30% of adults and 10% of children or adolescents in the US have hepatic steatosis, which is usually benign. However, about 3%-6% of the US population has NASH, which is a serious medical condition that may progress to hepatic fibrosis and cirrhosis leading to increased morbidity and mortality. A majority of patients diagnosed with NAFLD are asymptomatic. Liver biopsy is the current gold standard for the differential diagnosis of NAFLD and NASH; however, biopsy may be costly, invasive and subjective. A biomarker in blood may avoid a need for biopsy and provide early detection of NASH, which may improve patient treatment and outcome. While fatty liver disease may be diagnosed by MRI, currently there is no non-invasive determination that will differentiate between NAFLD and NASH.

Miniature Health-Care Ultrasonic Imaging System

The increasing market of mobile health indicates the growing consumer interest in low-cost and easy-to-use solutions for monitoring personal health. Weight, body-fat percentage and blood pressure are several critical indexes relating to a variety of chronic disease. Weight scale integrated with impedance measuring devices give a coarse full-body measurement on both weight and body-fat percentage but is susceptible to multiple error sources such as humidity. For fitness use, there is also lack of a device to monitor the effectiveness of local muscle building. On the other hand, current blood pressure gauge (sphygmomanometer) is hard to use without calibration and proficiency training. Both the devices are obviously too bulky to be portable and hence not a good solution for personal-health monitoring. Alternatively, ultrasonic imaging, now widely used in medical field, provides accurate and local body-index measuring such as local body-fat assessment by measuring real thickness of body-fat and blood-pressure measuring by Doppler imaging on blood flow speed. The accuracy and local-body part measuring solve the problems of traditional devices but the size, complexity and huge amount of power remains issues to be solved. To meet these challenges, investigators at the University of California, Davis and U.C. Berkeley have jointly developed a novel miniature, ultrasonic imaging system using a combination of microelectronic devices that measures the fat and muscle thickness at a particular human body part for health-care purposes and muscle-training monitoring. The system also has the capability of measuring blood flow and blood pressure. Due to the small size and single, low-voltage power supply of the system, this technology can also be integrated into portable devices for mobile health care.


Therapeutic inhibitors of Urea Transporter A (UT-A) as highly effective diuretics with reduced risk of cardiac and neurological side effects for treatment of cardiovascular and renal disorders

CYP3A4 Epoxygenase Inhibitors for ER+ Breast Cancer Treatment

Small molecule CYP34A inhibitor oncology therapeutics are being developed in collaboration between scientists at UC Irvine and U of Minnesota. These molecules have been shown effective against ER+ xenograft models of breast cancer. Due to their mechanism of action, these molecules may enhance treatment with tamoxifen and paclitaxel to decrease risk of recurrence.

Novel Mechanism Of Action For Diabetic Kidney Disease And For Novel Therapeutic

The search for biomarkers for kidney disease is considered a top priority by the NIH, FDA, and industry.  The current markers for kidney disease are blood creatinine and urine protein.  The blood creatinine is thought to reflect the filtration rate of the nephron possibly in the normal range, despite significant disease; in other instances the blood creatinine level may not indicate progression or improvement.  The urine protein may indicate leakage of blood protein into the urine and may indicate kidney disease in some but not all patients; in other instances the urine protein level may also not indicate whether the disease is improving or deteriorating.  Presently studies to evaluate therapies for kidney disease rely on the blood creatinine values and the urine protein.  However, both these measures do not reliably assess underlying kidney function and changes are not necessarily predictive of clinical outcomes.  Measurement of metabolites that are directly related to the pathogenesis of the disease process will likely be much more predictive and useful as a way to monitor kidney disease and therapies that are targeted at specific pathways.

High Resolution Depth of Interaction Gamma Radiation Detector

Researchers at UCLA have developed a method for improving the spatial resolution and sensitivity of gamma radiation detection for positron emission tomography (PET).

A Rapid, Reproducible, Non-Invasive Predictor of Cadaveric Donor Liver Graft Utilization

Dr. Zarrinpar in UCLA Department of Surgery has demonstrated the applicability of a rapid, non-invasive liver function test for quantitative assessment of cadaveric organ donor graft quality.

Mouse Model for Human Non-Alcoholic Steatohepatitis and Steatolic Hepatocellular Carcinoma

Currently, there are no good mouse models to study the development of non-alcoholic steatohepatitis (NASH) and its progression to steatolic hepatocellular carcinoma (HCC) in less than one year. While there are other models of NASH in mice, none of the currently available models closely mimics the human disease and most are models of toxic liver damage associated with weight loss rather than obesity. 

A Novel Peptide Therapy to Counteract Insulin Resistance and Type 2 Diabetes

To date, metformin and thiazolidinediones (TZDs) have been the only frontline drugs to treat insulin resistant and type 2 diabetic patients. However, with certain TZDs already withdrawn from the European markets and under intense FDA scrutiny in the US, it is crucial to explore new therapeutic agents for this disease. More recently, pioglitazone, another TZD, has been reported to increase the incidence of bladder cancer. Therefore there is an urgent need to develop new drugs to treat insulin resistance. One possible strategy focuses on the chromogranin A (CgA)-derived peptide pancreastatin (PST: hCgA250-301), which acts as an antagonist to insulin action. The lack of PST peptide in Chga knockout (Chga-KO) mice resulted in increased hepatic sensitivity to insulin; this hepatic sensitivity was shown to be abolished by PST supplementation.

Anti-Diabetic and Anti-Obesity Therapeutic

Obesity and its associated metabolic diseases, including type 2 diabetes, are components of a global epidemic.  However, the pharmacological approaches against obesity and metabolic diseases are limited. Research is growing on a secreted protein, Angiopoietin-like 4 (ANGPTL4), that inhibits lipoprotein lipase (LPL) activity and promotes lipolysis in adipocytes.  A UC Berkeley researcher is currently examining the role of ANGPTL4 and variants thereof, particularly the C-terminal fibrinogen-like domain (FLD) of ANGPTL4. Using animal models, the UC researcher found that increasing plasma FLD levels protected the animal from diet-induced obesity without affecting plasma triglyceride levels and improve glucose homeostasis. The discovery targets both white and brown adipose tissue, thus it provides a different approach to reduce obesity, complementing current pharmacological therapies.  In addition, the discovery provides compositions and methods to improve insulin sensitivity in type 2 diabetes patients.  

Noninvasive Screening for Gestational Diabetes

Dr. Brian Koos in the Department of Obstetrics and Gynecology at UCLA has developed a noninvasive and accurate screening technology to identify gestational diabetes during early pregnancy. 

Method for Comprehensive Profiling of Steroid Metabolome (Steroidome)

A researcher at the University of California, Davis has developed a method that allows for global profiling of the steroid metabolome (steroidome) in a single run lasting about 15 minutes, without the need for prior derivatization.

Novel Therapeutic Targets in Liver Fibrosis

Liver fibrosis often results from chronic liver pathologies, increasing the risk of cancer and even death by liver failure. Except for transplantation of the liver in advanced cases, current treatment for liver fibrosis is very limited although studies are underway to determine the mechanisms of fibrogenesis. New therapies will depend on learning the cellular events of fibrosis and finding druggable targets in those signaling pathways.

Anti-Diabetic Therapeutic Modulating Gpr43 Activity

Research is growing on how free fatty acids regulate metabolism by binding and signaling through G-protein-coupled receptors (GPCR). One such GPCR is GPR43 (also known as free fatty acid receptor 2 or FFAR2) which plays a broad role in numerous pathologies including inflammation, metabolic disease, and cancer. Consequently, the search for new GPR43 agonists has become the focus of numerous studies and drug discovery efforts.

Novel Gene Therapy Solution for Abnormal Fuel Metabolism and Diminished Contractile Function of the Diabetic Heart

Heart disease is a major factor in the mortality and morbidity associated with diabetes. Disturbances in key signaling pathways in cardiac myocytes alters fuel flux, increasing the diabetic heart’s reliance on fatty acids as fuel. This impaired substrate metabolism contributes to contractile dysfunction of the cardiac muscle ultimately leading to heart failure.

Shrink-Induced, Self-Driven Microfluidic Devices

The addition of novel surface modifications and use of shrink-wrap film to create devices will yield self-driven, shrink-induced microfluidic detection for samples such as bodily fluids. Novel fabrications and surfaces will have a profound impact on the creation of point of care diagnostics.

Anti-Obesity Compounds Derived from Neuromedin U

Researchers at UCLA have developed a highly stable neuromedin U (NMU) analog for the treatment of obesity and type 2 diabetes. 

Disialyl Glycans (As Immunoregulators, Prebiotics, And Antimicrobials) As Potential Therapeutics

Up to 20% of preterm infant deaths are caused by necrotizing enterocolitis (NEC). The American Academy of Pediatrics have shown that breast milk lowers rates of NEC in preterm infants, and while Disialyllacto-N-tetraose, a glycan in breast milk, has been identified to prevent necrotizing enterocolitis in newly born children, the cost of producing this glycan is too high. Researchers at the University of California, Davis have engineered a novel homolog to Disialyllacto-N-tetraose which has been shown to prevent necrotizing enterocolitis and can be produced quickly and cost-effectively.

Improved Treatment of Acute Metabolic Acidosis

Professors Thomas Mason and Jeffrey Kraut in UCLA’s Department of Chemistry and School of Medicine, respectively, have developed improved materials and methods of treating acute metabolic acidosis.

Single Chain Antibody to Oxidized Phospholipids as Treatment and Prevention for Inflammation

Oxidized phospholipids (oxPL) have been shown to be associated with many inflammatory diseases, and preventing oxPL from accumulating in the macrophages is believed to be a crucial step in reducing downstream inflammation events. Previously it has been shown that the innate natural antibody E06 blocks the uptake of OxLDL by macrophages by binding to the phosphocholine headgroup in OxPL molecules. It will be of interest to investigate if any therapeutic value can be derived from this finding.

Treating Type 2 Diabetes by Targeting CAP Protein in the Macrophage

CAP (Cbl associated protein) is an adapter protein that is ubiquitously expressed. CAP acts in concert with Cbl to stimulate glucose uptake in skeletal muscle and adipose tissue as well as to induce the proliferation and migration of macrophages. Whole body CAP gene deletion in mice results in a protection from insulin resistance induced by high fat diet. However, exercise capacity is severely blunted in these mice.

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