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A Tumorigenic Index to Determine Live Cancer Initiation and Prognosis

The incidence and mortality of liver cancer, mainly hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (ICC), are increasing rapidly worldwide. Diverse risk factors for primary liver cancer have been identified, including infection of hepatitis B virus (HBV) and hepatitis C virus (HCV), alcohol abuse and non-alcoholic steatohepatitis (NASH) as well as intake of aflatoxin B1. Consistent with the complex and multifactorial etiologies, multi-omics analyses of human HCC and ICC samples have identified vast genomic heterogeneity, molecular and cellular defects, metabolic reprogramming, and subtypes of tumors as well as altered tumor microenvironment in the liver. However, it remains to be determined if any common molecular signatures in the transcriptomes exist for liver cancer, despite their considerable genomic heterogeneity. Furthermore, little is known about the kinetics and fashions, either gradual accumulation or dramatic transition, in generation of cell-intrinsic and -extrinsic signals that are intertwined to drive malignant transformation of hepatocytes and tumor initiation.

Anti-Obesity Target

The global epidemic of type 2 diabetes is increasing at an alarming rate in both Westernized and developing countries. In the United States alone, it is estimated that there are at least 30 million people with this disease. Metabolic syndrome is 2 to 3 times more prevalent than type 2 diabetes and is usually the precursor state for this disease, indicating that this type 2 diabetes epidemic will not abate in the near future. Insulin resistance is a key etiologic feature of the metabolic syndrome and type 2 diabetes, and obesity is far and away the most common cause of insulin resistance in humans. There is a well-known parallel global epidemic of obesity, and the great majority of type 2 diabetic patients are obese. Therefore, it seems logical to conclude that the obesity epidemic is the underlying driver of the type 2 diabetes epidemic. Unfortunately, at the present time there are a limited number of therapeutics available as way of preventing or treating obesity.

Polaris: Lifestyle Guide for Diabetes

Researchers at UCI have developed a comprehensive platform, Polaris, for personalized diabetes management. By combining standard blood glucose monitoring with activity tracking, Polaris provides users with real-time suggestions that encourage treatment adherence and promote healthy behaviors to better mitigate their symptoms.

A Method to Prevent the Myelin Abnormalities Associated with Arginase Deficiency

UCLA researchers in the Department of Surgery have developed a gene therapy to prevent dysmyelination (and other CNS abnormalities) as a result of arginase deficiency.

Treatment for Restoring Ureagenesis in Carbamoyl Phosphate Synthetase 1 Deficiency

UCLA researchers in the Department of Surgery have developed a gene therapy to treat carbamoyl phosphate synthetase 1 deficiency.

Drug Repurposing To Explore Novel Treatment For Cushing Disease

UCLA researchers in the Department of Medicine and the Department of Molecular and Medicinal Pharmacology have identified several small molecule reagents to treat Cushing disease.

Prevention Of The Late Complications Of Acute Pancreatitis

UCLA researchers in the Department of Medicine and Surgery have developed a novel therapeutic for the prevention of late inflammatory complications in severe acute pancreatitis patients.

Targeting Sterol Transporters In Metabolic Disease

UCLA researchers in the Department of Pathology have characterized a novel mechanism of cholesterol transport in mammalian cells between plasma membrane the ER.  It is nonvesicular, lysosome independent and critical for lipid homeostasis.

Methods of Discovering New Bile Acids and Use in Treating Inflammatory Diseases

A mosaic of cross-phyla chemical interactions occurs between all metazoans and their microbiomes. In humans, the gut harbors the heaviest microbial load, but many organs, particularly those with a mucosal surface, associate with highly adapted and evolved microbial consortia. The microbial residents within these organ systems are increasingly well characterized, yielding a good understanding of human microbiome composition. However, we have yet to elucidate the full chemical impact the microbiome exerts on an animal and the breadth of the chemical diversity it contributes. A number of molecular families are known to be shaped by the microbiome including short-chain fatty acids, indoles, aromatic amino acid metabolites, complex polysaccharides, and host sphingolipids and bile acids. These metabolites profoundly affect host physiology and are being explored for their roles in both health and disease. The synthesis of bile acids takes place in the liver and recent research has shown that bile acids can act as signaling molecules and activate a number of molecules. A primary focus has been on the Farnesoid X receptor (FXR) which plays an important role in bile acid synthesis and in regulation of glucose, lipid and energy metabolism.

Circulating Lipidomic Signature To Identify Nonalcoholic Fatty Liver Disease

Fatty liver disease (or steatohepatis) is often associated with excessive alcohol intake or obesity, but also has other causes such as metabolic deficiencies including insulin resistance and diabetes. The causation of a fatty liver results from triglyceride fat accumulation in vacuoles of the liver cells resulting in decreased liver function, and possibly leading to cirrhosis or hepatic cancer. Non-alcoholic fatty liver disease (NAFLD) represents a spectrum of disease occurring in the absence of alcohol abuse. There is a clinical need for a simple test to identify individuals with nonalcoholic fatty liver disease (NAFLD) in the population. While circulating lipids have been used for this purpose, the large number of analytes within the human lipidome makes it cumbersome to utilize this approach for high throughput screening.

Mitochondrial Respirometry In Frozen Specimens

UCLA researchers from the Department of Medicine have developed a novel technique for performing mitochondrial respirometry in frozen specimens to accurately assess the cellular energy production capacity.

A Method and Device for the Estimation of Blood Glucose Concentration from Signals of Sensors Implanted in Tissues

Diabetes is a major disease affecting all populations and age groups, and society as a whole. All therapies for diabetes are based on achieving close glucose control. Close glucose control achieved by sufficient and timely administration of therapy has been shown to reduce the destructive “long-term complications” of diabetes, such as retinal damage, kidney failure, amputations, and cardiovascular damage, as well as debilitating and life-threatening short-term hypoglycemia. However, attainment of close control requires a means of glucose monitoring and means for correction of glucose imbalances such as administration of insulin, pharmaceuticals, diet adjustment, and exercise, based on the monitored glucose concentration.

Combination Immunotherapies for Treatment of Liver Cancer

Primary liver cancer, with the majority being hepatocellular carcinoma (HCC), is now the second leading cause of cancer mortality and the fifth most common cancer worldwide, claiming approximately 800,000 life every year. HCC is a chemotherapy resistant tumor with limited treatment options including surgical resection, liver transplantation and local ablation at the early stages. Sorafenib, a multi-kinase inhibitor, remains a first-line systemic drug for advanced HCC even with poor outcomes, and similar low therapeutic benefits were reported for regorafenib, lenvatinib, and cabozantinib. Over 100 clinical trials that tested other compounds or approaches have failed to show therapeutic benefit to HCC patients. Immunotherapy by blocking inhibitory pathways in T lymphocytes, such as the PD-L1/PD-1 axis, is being widely tested in various solid tumors. Notably, this emerging therapeutic approach is already in clinical trials for advanced HCC in multi-centers around the globe. Two latest reports on open-label, non-randomized, phase 1/2 trials with pembrolizumab or nivolumab indicated manageable safety in advanced HCC patients with or without prior sorafenib treatment, albeit with very limited therapeutic benefits observed so far. The outcome of immunotherapy for liver cancer can be compounded by the unique immunotolerant microenvironment in the liver. A variety of clinical trials are ongoing to evaluate combination of immune checkpoint inhibitors or with other drugs, without clear justification or support by preclinical data.

MiR-22 as a Potential Treatment Target for Steatohepatitis and Type 2 Diabetes Mellitus

Researchers at the University of California, Davis have developed miR-22 inhibitors as a potential treatment for metabolic syndrome.

Three-Step Method For Universal Enrichment, Expansion, And Maturation Of Skeletal Muscle Cells Derived From Human Pluripotent Stem Cells

UCLA researchers have developed a novel method for enriching, expanding, and maturing populations of skeletal muscle progenitor cells (SMPCs) from human pluripotent stem cells (hPSCs).

Methods And Devices for Continuous Analyte Sensing with Microporous Annealed Particle Gels

UCLA researchers in the Department of Bioengineering have developed novel microporous annealed particle gels for long-term continuous monitoring of blood metabolites.

The Use Of Parathyroid Gland Cells And Their Secreted Factors To Promote Islet Beta Cell Engraftments

This invention identifies a novel method to increases survival of transplanted islets in extra-hepatic sites (subcutaneous and intramuscular) through co-transplantation of pancreatic islet beta cells together with parathyroid glands (PTGs). This treatment can successfully be used for patients with type I diabetes.

Liquid Biopsy Diagnostic for Precursor Lesions of Pancreatic Cancer

These highly specific biomarkers distinguish potentially malignant mucinous cysts from benign nonmucinous cysts in the pancreas to help diagnose precursor lesions of pancreatic ductal adenocarcinoma. The biomarkers can be detected through enzymatic assays with exceptional accuracy and sensitivity.

Identification Of OLMAINC as a Biomarker for NAFLD, NASH, Metabolic Syndrome, Hepatic Fibrosis

UCLA researchers in the Departments of Medicine and Human Genetics have identified a sequence of long, non-coding RNA that plays a role in the regulation of intracellular lipogenesis and holds potential for diagnosing and treating metabolic diseases, including NAFLD and NASH.

AGPAT5 as a Molecular Mediator of Insulin Resistance

UCLA researchers in the Departments of Medicine and Cardiology have identified a novel gene and pathway in the regulation of insulin sensitivity and discovered an inhibitor of this gene useful for treating AGPAT5-related diseases.

Novel Targets And Use Of Small Molecule BT-2 To Treat Heart Failure, Obesity And Diabetes

UCLA researchers from the Cardiovascular Theme in the Departments of Anesthesiology, Physiology and Medicine have discovered new pathways and potential treatment options for heart failure, obesity, and diabetes

High Frequency Digital Frequency Domain Fluorescence Lifetime Imaging System For Applications On Tissues

The technology is a software/hardware combination designed to enhance sampling rate for frequency domain fluorescence lifetime imaging. Fluorescence lifetime imaging microscopy (FLIM) is a technique that uses signals emitted from fluorescent samples to construct images of those samples in near real time. An advantage to FLIM is its ability to image large fields of view, which makes it an attractive option for dynamical measurements of live biological tissues. The higher sampling rate available using this technology will allow for more information to be gleaned from biological samples, which may have a fluorescence band up to 1 GHz, advancing tissue imaging.

TREATING TYPE-1 DIABETES BY PRESERVING BETA CELL FUNCTION

This invention proposes the first pharmacological treatment to prevent the onset of Type I diabetes by preventing beta cell destruction. 

Novel Anti-Bacterial, Anti-Fungal Nanopillared Surface

Medical devices are susceptible to contamination by harmful microbes, such as bacteria and fungi, which form biofilms on device surfaces. These biofilms are often resistant to antibiotics and other current treatments, resulting in over 2 million people per year suffering from diseases related to these contaminating microbes. Death rates for many of these diseases are high, often exceeding 50%. Researchers at UCI have developed a novel anti-bacterial and anti-fungal biocomposite that incorporates a nanopillared surface structure that can be applied as a coating to medical devices.

A Method for Inhibition of de novo Lipogenesis

The obesity epidemic currently afflicting the US and other developed countries has resulted in a marked increase in the incidence of the metabolic syndrome and its associated pathologies, including nonalcoholic fatty liver disease (NAFLD), estimated to affect 30% of Americans. Although NAFLD is characterized by lipid droplet buildup in hepatocytes, it is not accompanied by liver damage, inflammation, and fibrosis unless combined with other risk factors, such as endoplasmic reticulum (ER) stress or mitochondrial dysfunction. In the context of simple, nonsymptomatic liver steatosis, ER stress or mitochondrial dysfunction trigger nonalcoholic steatohepatits (NASH), a serious disease that can progress to liver cirrhosis, resulting in loss of liver function, and hepatocellular carcinoma (HCC), one of the most deadly cancers. The obesity epidemic currently afflicting the US and other developed countries has resulted in a marked increase in the incidence of the metabolic syndrome and its associated pathologies, including nonalcoholic fatty liver disease (NAFLD), estimated to affect 30% of Americans. Although NAFLD is characterized by lipid droplet buildup in hepatocytes, it is not accompanied by liver damage, inflammation, and fibrosis unless combined with other risk factors, such as endoplasmic reticulum (ER) stress or mitochondrial dysfunction. In the context of simple, nonsymptomatic liver steatosis, ER stress or mitochondrial dysfunction trigger nonalcoholic steatohepatits (NASH), a serious disease that can progress to liver cirrhosis, resulting in loss of liver function, and hepatocellular carcinoma (HCC), one of the most deadly cancers.

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