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Peptide Inhibitors of Human Voltage Gated Proton Channel hHv1 Activity to Reduce Inflammation

Human voltage-gated proton channels (hHv1) are implicated in a wide range of biological responses, including capacitation of sperm and stimulation of the innate immune response. Human sperm undergo a process called capacitation in the female reproductive tract, whereby intracellular pH rises and stimulates a progesterone-induced Ca2+ influx.  Researchers at the University of California, Irvine have discovered that this calcium influx is controlled by albumin activation of Hv1 voltage-gated proton channels.  Albumin activation of hHV1 in neutrophils also supports production and release of reactive oxygen species and protease during the immune respiratory burst.  These findings demonstrating a stimulatory role of albumin in both sperm and neutrophils has led to new therapeutic approaches to fertility and the treatment of inflammatory diseases.

Potent MMP-12 Inhibitors as a Therapy for COPD and Asthma

Prof. Maurizio Pellecchia and his colleagues at the University of California, Riverside (UCR) have developed novel MMP-12 inhibitors with single-digit nanomolar activity. These agents, are highly selective for MMP-12 with appreciable inhibition of only MMP-3.  When compared to a known MMP-12 inhibitor, MMP408, the UCR MMP-12 inhibitors are 5 times more potent than MMP408.To examine their efficacy, the UCR MMP-12 inhibitors were tested in a well-established murine model of elastase-induced emphysema. After treatment, it was determined that the mice treated with the MMP-12 inhibitors exhibited significantly less lung damage than the controls.   Fig. 1 Docked geometry of one of the UCR MMP-12 inhibitors in complex with MMP-12.    Fig. 2 Effects of MMP-12 inhibition on lung tissue destruction in a murine model of elastase-induced emphysema. Mice were challenged with a single intranasal instillation of porcine pancreatic elastase (PPE), then treated daily for 7 days with vehicle control or MMP-12 inhibitors MMP408, compound 25, or compound 26. After 21 days, the mice were examined and data gathered on how they responded. Mice exposed to PPE but treated with MMP-12 inhibitors (MMP-408, compound 25, or compound 26) exhibited a significant decrease in emphysema-like pathology compared to PPE + vehicle-treated mice, with measurements for mice treated with PPE + MMP-12 inhibitors exhibiting no significant differences compared to the control, saline treated mice.

Anti-microbial, Immune-modulating, Naturally-derived Adjunctive Therapies

Researchers at the University of California, Davis have developed adjunctive therapies applicable to multiple types of infectious conditions. These therapies – derived from compounds found in natural herbs - also have potential prophylactic efficacy.

Photoacoustic Spectroscopy Detection Of HFA, NO, And C02 From Exhaled Breath

UCI researchers introduced a medical device which simultaneously detects hydrofluoroalkane (HFA), carbon dioxide (CO2), and nitrogen monoxide (NO) in exhaled breath for monitoring and improving treatment of asthma and chronic obstructive pulmonary disease (COPD).

MicroRNA regulation of airway mucins for treatment of lung diseases

This invention describes a novel therapeutic microRNA target regulating mucus production for the management of symptoms caused by a range of lung diseases, including asthma, chronic obstructive pulmonary disease (COPD), cystic fibrosis, and the common cold. Recently, a specific miRNA, along with its highly homologous family members, has been shown to be dysregulated in asthmatic subjects. To modulate the effect of these miRNAs, antagomirs (which target specific endogenous miRNAs and dampen their effect) or miRNA mimics can be administered via an inhaler, allowing for the regulation of mucus production. This invention is at the preclinical stage, and in vivo testing in a mouse model of asthma has shown that treatment with a specific miRNA antagomir results in a significant reduction of airway mucus production. While there are currently no effective therapies targeting mucus production in the airways, miRNAs are a promising new avenue for therapeutic intervention as they are fast-acting and reversible. 

A Point Of Care Method To Detect Covid19 Infected And Immune Patients For Pennies

The emergence of a novel coronavirus disease (COVID-19) in late 2019 has caused a worldwide health and economic crisis. Determining which members of the population are infected is key to re-opening of schools, universities, and non-essential businesses. To address this, researchers at UCI and UIC have developed an inexpensive point of care test using RNA aptamer technology for detecting COVID19 infected and immune patients that can be taken at home like a pregnancy test.

Mapping Ciliary Activity Using Phase Resolved Spectrally Encoded Interferometric Microscopy

Researchers at UCI have developed an imaging technique that can monitor and measure small mobile structures called cilia in our airways and in the oviduct. This invention will serve as a stepping stone for study of respiratory diseases, oviduct ciliary colonoscopy and future clinical translations.

Polarization-Sensitive Optical Coherence Tomography Using a Polarization-Insensitive Detector

A polarization-sensitive optical coherence tomography (PS-OCT) is a common approach to non-invasively imaging in biomedical applications. The inventors have come up with a new way of creating a PS-OCT that is cheaper and simpler.

Use of inhibitors and cell based therapies to combat a fatal immune response in COVID-19

UC researchers sought to define the host immune response, the “cytokine storm” , that has been implicated in fatal COVID-19 using an AI-based approach. Over 45,000 publicly available transcriptomic datasets of viral pandemics were analyzed to extract a 166-gene signature. The signature was surprisingly conserved in all viral pandemics, including COVID-19, inspiring the nomenclature ViP-signature. A subset of 20-genes classified disease severity in respiratory pandemics. The ViP signatures pinpointed airway epithelial and myeloid cells as the major contributors of an IL-15 cytokine storm, and epithelial and NK cell destruction as determinants of severity/fatality. They also helped formulate precise therapeutic goals to reduce disease symptoms and severity. Thus, the ViP signatures provide a quantitative and qualitative framework for titrating the immune response in viral pandemics and may serve as a powerful unbiased tool in our armamentarium to rapidly assess disease severity and vet candidate drugs. 

Development of a Thermal Endoscope for ENT Clinical Diagnostics

There is a clinical need for improved visual inspection for ENT diagnosis and surgeries. Endoscopy is required to access locations of ENT conditions. However, the assessment and identification of ENT abnormalities and pathologies remain challenging due to the difficult-to- reach ENT locations and the complex nature of the related pathologies. An imaging technique that could provide additional information, high contrast, and quantitative data about the patient condition will be useful, especially to assist ENT clinicians in diagnosis and surgeries and to avoid the need to resort to more expensive imaging techniques (e.g., CT scans, ultrasound imaging,MRI).

Live Attenuated Vaccine Against Group A Streptococcus Infection

Streptococcus pyogenes (group A Streptococcus [GAS]) is a leading health and economic burden worldwide, with an estimated 700 million infections occurring annually. Among these are 18.1 million severe cases that result in over 500,000 deaths. Despite active research, a protective vaccine remains elusive, leaving antimicrobial agents as the sole pharmacological intervention against GAS. To date, penicillin remains a primary drug of choice for combating GAS infections. However, despite no apparent emergence of resistant isolates, the rate of treatment failures with penicillin has increased to nearly 40% in certain regions of the world. Due to the high prevalence of GAS infection and the decreasing efficacy of the available repertoire of countermeasures, it is critical to investigate alternative approaches against GAS infection. An emerging strategy for combating pathogenic bacteria involves targeting virulence. To avoid immune clearance, GAS expresses a wide variety of secreted and cell-associated virulence factors to facilitate survival during infection. Despite decades of inquiry into the role and regulation of GAS virulence factors, the function and potential importance of many proteins involved in pathogenicity remain unknown.

A Fully‐automated Deep Learning System (software code) for the Detection, Prognosis, and Visualization of Pulmonary Disease.

The majority of state‐of‐the‐art lung segmentation algorithms in the literature do not simultaneously segment lungs, lung lobes, and airway in a single algorithm. Additionally, automated algorithms typically perform the segmentation task on a series of 2D slices, which can reduce segmentation accuracy of anatomical structures (i.e. lung lobes) that may require contextual information across all three spatial dimensions. Many existing algorithms also have not been validated on chest CTs across a wide variety of conditions to evaluate algorithm generalizability. Currently, quantification of respiratory measurements requires a radiologist, trained analyst, or technician to recognize, identify, and manually annotate anatomical landmarks such as the lung lobes or airway in the chest. A fully‐automated deep learning system may eliminate the need for manual analysis, thereby improving efficiency and expanding applicability to a large number of CTs.

TRM: HIF-1 alpha KO Mice (CRE)

Hypoxia-inducible factor 1-alpha is a transcriptional regulator of the adaptive response to hypoxia. When activated under hypoxic conditions, it can turn on over 40 genes involved in a variety of physiological activities. The dysregulation or alteration by mutation can lead to pathophysiology in areas of energy metabolism, cancer, cell survival and tumor invasion.

Techniques for Improving Positron Emission Tomography Image Quality and Tracking Real-Time Biological Processes

Researchers at the University of California, Davis have developed methodologies that perform dynamic PET imaging and provide opportunities for tracing blood flow and other biological systems in real-time.

Engineered Biomaterial to Prevent Endothelial Inflammation

Researchers at the University of California, Davis have developed a biocompatible material to mimic the glycocalyx, the natural layer of molecules that coats the outside of endothelial cells. This technology can be used to treat inflammation in diseases characterized by dysfunction in leukocyte-endothelial cell interactions.

Small Molecule Pendrin Inhibitors for Treatment of Inflammatory Airway Diseases and Diuretic Resistance

Small molecule pendrin inhibitors for treating inflammatory lung diseases.

A Simple Integrated Device For Assessing Lung Health

Chronic lung diseases, like asthma, impose critical challenges on both the patients and the physicians due to the complexity of the diseases. Not only are these diseases tough to accurately assess, many of the diseases can be impacted by other physical and sociological factors. Perhaps a greater difficulty lies in measuring the effectiveness and compliance of the medications including inhaled medications. The invention discovered at the University of California, Irvine, is an “all-in-one,” portable device that offers complete assessment of lung health. It also incorporates a novel technology for monitoring the effectiveness and compliance of a medication, thereby, providing a personalized treatment and care plan for adults and children with asthma.

Endoscopic Optical Coherence Tomography As A Minimally Invasive Lung Cancer Screening Tool To Guide Diagnosis And Therapy

Current diagnostic procedures for lung cancer are invasive, time-consuming, and subjective. UCI researchers have developed a quick, non-invasive lung cancer diagnostic device which uses optical coherence tomography (OCT) and can improve lung cancer diagnosis and outcomes.

“CT Mucus Score” - A New Scoring System that Quantifies Airway Mucus Impaction Using CT Scans

A novel method to measure airway mucus plugging using CT images from patients with asthma or chronic obstructive pulmonary disease (COPD) patients.

Potent TMEM16A Small Molecule Treatment for Inflammatory and Reactive Airway Diseases, Asthma, Hypertension, Pain and Cancer

A novel class of 2-acylamino-cycloalkylthiophene-3-carboxylic acid arylamides (AACTs) as potent TMEM16A inhibitors

Novel Use of Chitinases for Treatment of Lung Inflammatory and Fibrotic Diseases

A novel approach for the treatment of lung inflammatory and fibrotic diseases by increased or repaired chitinase function in lung tissues

Technique for Respiratory Gated Radiotherapy using Low Frame Rate MRI and a Breathing Motion Model

UCLA researchers in the Department of Radiation Oncology have developed a novel method to gate radiotherapy using low frame rate MRI sequences to reduce damage to adjacent tissues during radiotherapy.

Respiratory Monitor For Asthma And Other Pulmonary Conditions

A patch sensor that is able to continuously monitor breathing rate and volume to diagnose pulmonary function and possibly predict and possibly prevent fatal asthma attacks.

METHOD FOR DETECTING AND TREATING NASAL AND LUNG DYSBIOSIS PATIENTS WITH MICROORGANISMS

This invention uses sequencing of microbiota community for diagnosis and treatment of lung and nasal dysbiosis.

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.

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