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Generation Of Human Beta Cell Equivalents From Pluripotent Stem Cells In Vitro

This invention describes a robust method to generate functional human beta cell equivalents from pluripotent stem cells in vitro for wide applications in basic research, drug and toxicology screens and as a diabetes cell therapy.

Predicting Weight Loss And Fat Metabolism Using Optical Signal Changes In Fat

Researchers at UCI have developed a novel use of an emerging functional imaging technology, Diffuse Optical Spectroscopic Imaging (DOSI), for monitoring changes in subcutaneous adipose tissue (“AT” also known as “fat” tissue), structure and metabolism during weight loss. Changes in subcutaneous adipose tissue structure and metabolism have been shown to correlate with the development of obesity and related metabolic disorders. The invention is a diagnostic tool that assesses the structure and function of fat tissue in vivo.

A Thin Film Cell Encapsulation Device

This invention is a macroencapsulation device for cell transplantation that addresses the challenges of micro- and macroencapsulation devices. The device’s thin film design allows for diffusion and flexibility like a microencapsulation device, while its macro-size allows for precise pore control and device retrievably.

Novel Compounds Targeting LRH-1for Treatment of Inflammatory Bowel Disease, Type II Diabetes, Triple Negative Breast Cancer & Pancreatic Cancer

This technology contains a method for modulating the activity of the nuclear receptor LRH-1 with identified small molecule compounds that may be developed to treat inflammatory bowel disease, Type II diabetes, triple negative breast cancer and pancreatic cancer.

Methods and Compositions of Treating Diabetic Nephropathy and Insulin Resistance

Researchers at the University of California, Davis have developed novel methods and compositions for the treatment of diabetic nephropathy and insulin resistance.

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.

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.

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. 

Strategy To Eliminate Extracellular Lactate Using Small Molecules That Directly Bind Lactate and Affect its Metabolism

Enhanced extracellular lactate levels play a central role in the pathophysiology of obesity, cancer, lactic acidosis, and lactate associated genetic disorders. During liver and kidney dysfunction, lactate builds up and leads to lactic acidosis, which could be fatal. Traditionally, dichloroacetate and phenylbutyrate have been used to decrease extracellular lactate levels, which do not change the pH levels or mortality. In some cases, intravenous injection of bicarbonate is also used, which increases the pH and pCO2 levels, but does not clear lactate from the blood. The extracellular lactate levels are a hallmark of several diseases, but have not been targeted because of difficulty in designing small molecules that can bind and eliminate it. It is difficult to eliminate because monocarboxylate transporters (MCTs) require a proton as the counter ion, leading to intracellular acidification, and kidney actively transporting lactate back into the blood.  Scientist at UC Berkeley have invented a strategy of passively eliminating extracellular lactate via forced intracellular transport of sodium lactate and enhancement of its metabolism into pyruvate by directly binding lactate to a small molecule. They successfully demonstrated that binding of this molecule converts the lactate log P to 0.6 from -0.6, and makes lactate available for intracellular metabolism. They have utilized the effectiveness of enhanced lactate metabolism in vivo by using a small molecule to normalize the blood pH of metformin treated mice to 7.18±0.13 from 6.67±0.09 and decrease the blood lactate level by 2 to 4 fold. This first generation class of molecule can be utilized to modify lactate metabolism by specifically binding to lactate, and therefore have a large impact in several diseases needing modification of lactate metabolism.

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.

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