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Human-Centered Drug Discovery: A Methodology To Identify And Validate High-Value Therapeutic Targets For Human Diseases

Modeling diseases as networks has helped simplify an otherwise complex web of multi‐cellular processes; however, an exclusive reliance on symmetric relationships in these networks overlooks the existence of disease continuum states and loses information relevant to pathogenesis and for the development of therapeutics. Network‐based analyses severely influenced by symmetric analyses have helped formalize Network Medicine as a field and deliver many successes, but drugs that can predictably re‐set the network in complex multi‐component diseases are yet to emerge.

A Tumorigenic Index to Determine Liver 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.

Assay for Chronic Wound Biofilm Disruptors

Dr. Manuela Martins-Green’s UCR laboratory has developed a new assay to identify medicines that disrupt chronic wound biofilms in patients.  A patient’s wound biofilm is collected with a sterile swab and the bacteria collected from the swab are cultured and identified.  The bacteria are then used singly or in combination, to make a biofilm in 96 well plates to then be used for high throughput screening using a multitude of antibiotics, chemical and small molecules that may be tested alone or in combination for their ability to disperse the wound’s biofilm. Fig. 1 shows the biofilm cultures from chronic wound patient isolates. The biofilm is made more easily visible by staining with crystal violet. Fig. 2 Different concentrations of an antimicrobial drug ranging from 3 to 20 mg/ml were applied at 0, 6, 12, and 24 hours after the biofilm cultures were initiated. When applied at time zero the bacteria will not grow or form biofilm. This is akin to application after debridement. When applied after the biofilm has been formed it will dismantle the biofilm when used at the right concentrations. Akin to treating without debridement.  

A Microplatform For Performing High Throughput, Multiplexed Assays On Adherent Cells

Systems and methods are providing for performing high-throughput, programmable, multiplexed assays of biological, chemical or biochemical systems. Preferably, a micro-pallet includes a small flat surface designed for single adherent cells to plate, a cell plating region designed to protect the cells, and shaping designed to enable or improve flow-through operation. The micro-pallet is preferably patterned in a readily identifiable manner and sized to accommodate a single cell to which it is comparable in size. Each cell thus has its own mobile surface. The cell can be transported from place to place and be directed into a system similar to a flow cytometer. Since, since the surface itself may be tagged (e.g., a bar code), multiple cells of different origin and history may be placed into the same experiment allowing multiplexed experiments to be performed.

A Wearable Platform for In-Situ Analysis of Hormones

UCLA researchers in the Department of Electrical and Computer Engineering have developed a highly sensitive, wearable hormone monitoring platform.

Use of Machine Learning to Predict Non-Diagnostic Home Sleep Apnea Tests

Researchers led by Robert Stretch from the Division of Pulmonary, Critical Care & Sleep Medicine at UCLA have developed an algorithm that can predict whether a patient will have a non-diagnostic home sleep apnea test based upon data from the electronic health record and a brief questionnaire.

Identification Of Pan-Cancer Small Cell Neuroendocrine Phenotypes And Vulnerabilities

UCLA researchers in the Department of Molecular and Medical Pharmacology have developed a classifier for the identification and treatment of small cell neuroendocrine cancers and small-round-blue cell tumors not previously identified.

Noninvasive Method and Apparatus for Peripheral Assessment of Vascular Health

UCI researchers introduce a medical device which noninvasively and accurately monitors vascular health metrics such as endothelial function, arterial stiffness, and blood pressure.

Automatic Identification of Ophthalmic Medication for The Visually Impaired

Researchers at UCI are developing technology that allows visually impaired patients to use their smartphones to take pictures of their eye medication/eye drop bottles. The technology will recognize the eye medication and verbally communicate the medication and will audibly confirm the medication along with the instructions on use.

Continuous, Quantitative, Selective, Non-Enzymatic Glucose Monitoring Using Conductimetric Analysis

A new molecule that enables glucose monitoring using measurements of solution conductivity. 

Clinical Prognostication Test In Uveal Melanoma

Uveal melanoma commonly known as ocular or choroidal melanoma, is a rare cancer of the eye. It is an intraocular malignancy that arises from melanocytes of the choroid, ciliary body, and iris of the eye. Ocular melanoma is diagnosed in approximately 2,000-2,500 adults annually in the United States. In both the U.S. and Europe, this equates to about 5 - 7.5 cases per million people per year and, for people over 50 years old, the incidence rate increases to around 21 per million per year. While the primary tumor is highly treatable, about half of the patients will develop metastasis —typically to the liver. Metastatic disease is universally fatal. While traditional staging methods such as tumor size and location, still play a role in assessing metastatic risk, they are rarely used to individualize patient management plans. Newer methods include chromosomal gene expression analysis, yet these methods have their technical limitations. Clearly, what is needed is a better, cheaper and reproducible prognostic test.

Simple Imaging Tool for Oral Cancer Detection and Monitoring

UCI researchers have developed a miniature, flexible intra-oral probe with a camera that allows early detection of oral cancer lesions in difficult-to-see, high risk areas of the mouth and throat. The tool allows for a low cost, non-invasive procedure that can be easily adopted in non-specialist medical settings.

At Home Fetal Electrocardiogram/Heartrate Monitor for Congenital Heart Defect Diagnosis

Congenital heart defects affect >1% of babies born in the United States. These defects originate early on in fetal development. Inventors at UC Irvine have developed a flexible medical device that allows at home fetal electrocardiogram (ECG) monitoring to diagnosis congenital heart defects during development.

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.

“Polyp-Print”: A Methodology To Identify Which Colon Polyps Are Likely To Proceed To Colorectal Cancers

Colorectal cancer (CRC) is the second leading cause of cancer deaths in men and women combined in the United States, according to the American Cancer Society. Every day, patients undergo routine screening colonoscopies around the world for assessment of their risk of CRC. CRCs always arise from precursor lesions, called polyps. Since most patients with polyps are asymptomatic, tracking these lesions through fecal occult blood, rectosigmoidoscopy and colonoscopy enables the suspicion, detection and removal of the lesion. Since 2000, colonoscopy has become the most important examination to track polyps and CRC. Nowadays, in the USA, one out of four colonoscopies aim to track polyps. Besides detecting polyps, their removal through endoscopic polypectomy has proved to be effective to reduce the incidence of this tumor. Anatomopathological analysis enables the histological classification of adenomas, and also allows checking for dysplasia or neoplasm, as well as vascular and/or lymphatic invasion. This assessment determines if polypectomy and/or mucosectomy were effective to heal the patient who presented with polyp or CRC, or if therapeutics will be necessary. Typically, screening colonoscopies begin at age 50, and are done every 10 years. If polyps are encountered, based on their size and number and location, the risk is determined to be high vs low (completely arbitrarily, with no molecular basis at all). Bottomline, right now, there is no way to tell which polyp will become a cancer and which will not. Hence, some patients may be receiving over Rx and some may be under Rx. Clearly, what is needed is an invention that can predict the timing and consequences of multiple host events during CRC initiation and progression.

Method for the detection of specific cells in bodily fluids with a small fluorescent probe

Using standard cellular biology techniques, researchers at UCI have developed a method for detecting the cellular components of blood easily, cheaply, and quickly with accurate quantification using fluorescence techniques.

Very-Small-Nuclear Circulating Tumor Cell (vsnCTC) as a Diagnostic Biomarker of Visceral Metastasis in Advanced Prostate Cancer

UCLA researchers in the Department of Molecular and Medical Pharmacology have identified a novel biomarker that can be used to diagnose prostate cancer patients for the presence of visceral metastasis with 54% sensitivity and 100% specificity.


The emergence of several cell based therapy candidates in the clinic is an encouraging sign for human diseases/disorders that currently have no effective small molecule or biologic based therapy. Stem cells – including adult and pluripotent subtypes – offer tremendous clinical promise for the treatment of a variety of degenerative diseases, as these cells have the capacity to self-renew indefinitely and to mature into functional cell types and thereby serve as a source of cell replacement therapies (CRTs) and pluripotent stem cells (hPSCs) are of increasing interest for the development of CRTs because of their capacity to differentiate into all cell types in an adult, for which adult tissue-specific stem cells may in some cases not even exist. One potential CRT enabled by hPSCs is oligodendrocyte progenitor cells (OPCs) for the treatment of spinal cord injury (SCI). Such hPSC-OPCs have recently advanced to a Phase II clinical trial and are even being considered for additional diseases in the central nervous system (CNS), such as multiple sclerosis (MS), or injury from radiation.   UC researchers have developed a microscale 3D culture screening and analysis methodology that is relevant to the production of several up and coming cell replacement therapy candidates for which derivation from a precursor cell type requires searching through a large in vitro design space of doses, durations, dynamics, and combinations of signaling cues over several weeks of culture, such as oligodendrocyte progenitor cells (OPCs) and midbrain dopaminergic neurons (mDA neurons) derived from human pluripotent stem cells. 

DARTS: Deep Learning Augmented RNA-seq Analysis of Transcript Splicing

Researchers led by Yi Xing have developed a novel deep learning algorithm to detect alternative splicing patterns in RNA-seq data

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.

A Method For Digital Pathology Using Augmented Reality

UCLA researchers in the Departments of Electrical Engineering and Computer Engineering have developed a novel method for automated image analysis of digital pathology slides.

A High Potency CYP3A4 Inhibitor for Pharmacoenhancement of Drugs

      CYP3A4 is the most clinically relevant drug metabolizing enzyme in the body, as it is responsible for the oxidation and breakdown of ~60% of current drugs on the market.  Researchers at UCI have developed novel CYP3A4 inhibitors, that are highly potent and more specific, exhibit fewer side effects, and are both cheaper, and easier to-synthesize than current commercially available CYP3A4 inhibitors. 

Prediction Tools for Vedolizumab Drug Exposure and Efficacy for Ulcerative Colitis and Crohn’s disease

Vedolizumab (VDZ) is an effective therapy for the management of patients with moderately to severely active ulcerative colitis (UC) or Crohn’s disease (CD) who have failed conventional therapy with aminosalicylates, corticosteroids, and thiopurines, as well as biologic therapy with tumor necrosis factor (TNF) antagonists. Several studies have identified potential predictors of treatment outcomes; however, the optimal approach to integrating predictors into routine practice is uncertain.No prior decision support tools exist to predict VDZ drug exposure in UC and CD and link this back to differences in effectiveness or response to VDZ dose escalation. By having a tool that can predict at baseline prior to start of therapy whether VDZ will be effective and what a patients drug exposure profile will be with VDZ, the provider can 1) determine if VDZ is an appropriate therapy to begin, 2) proactively monitor those patients deemed high risk for treatment failure with VDZ, and 3) proactively measure drug concentrations for VDZ to then increase the dose or the interval at which VDZ is administered to improve outcomes.

Novel Synthesis of Streptogramin A Antibiotics

A modular, scalable, chemical synthesis platform that produces new Streptogramin A class antibiotic candidates.

A New Human-Monitor Interface For Interpreting Clinical Images

UCLA researchers in the Department of Radiological Sciences have invented a novel interactive tool that can rapidly focus and zoom on a large number of images using eye tracking technology.

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