University of California Center for Accelerated Innovation

Funded Technologies

Spring 2016 NHLBI Awardees

Title Type Disease Area Description Indication PI

Protein Tyrosine Phosphatase Inhibitors for Hematopoietic Regeneration

Therapeutic Blood

We have discovered a receptor protein on blood stem cells that regulates the growth and survival of the blood stem cell.  We have subsequently developed a therapeutic that binds to this receptor and causes blood stem cells to grow and regenerate following exposure to medically relevant toxins such as chemotherapy and radiation therapy. We are developing this novel therapeutic for a first generation treatment for patients receiving chemotherapy, radiation therapy or stem cell transplantation as a means to accelerate blood and immune system recovery and to improve survival.

Self-renewal or regeneration of hematopoietic stem cells (HSC)


John Chute
UCLA

Pro-resolving Micro-/nano-particles to Improve Vascular Patency

Therapeutic Multiple Diseases

Recurrent narrowing of blood vessels following interventions such as angioplasty, stenting, and bypass surgery remains a common and costly problem in cardiovascular disease management. Inflammation is recognized as having a central role in the vascular injury response. We have demonstrated that DHA-derived SPM (D-series resolvins) have potent biologic effects on vascular tissues that collectively reduce inflammation, promote vessel healing and reduce unwanted scarring. We now seek to further the development of this strategy by developing novel nano-particle formulations encapsulating a recently described synthetic SPM analogue, with enhanced bioavailability. These products will represent a new class of anti-restenosis therapies with an enhanced safety profile and wide applicability, addressing a major unmet need in cardiovascular surgery and intervention.

Artherosclerotic cardiovascular disease and peripheral arterial disease


Michael Conte 
UCSF

Data Fusion and Analytics to Predict In-hospital Cardiopulmonary Arrests and Reduce Alarm Fatigue

Device Cardiovascular

In-hospital cardiopulmonary arrest is a major public health issue with more than 200,000 victims per year. SuperAlarm is a predictive analytics software solution that aims to identify at-risk patients prior to a catastrophic cardiopulmonary arrest using a machine learning approach. SuperAlarm is able to predict patient deterioration through monitoring alarm patterns, primary waveform analysis, and laboratory results. Current algorithm performance suggests that SuperAlarm can identify 90% of cardiopulmonary arrest victims with at least a 2-hour warning, which would allow further actions and interventions to change the outcomes of critically ill patients.

Prediction of cardiopulmonary arrest and cardiopulmonary instability


Richard Fidler
UCSF

Improving Outcomes of Cardiac Resynchronization Therapy

Device Cardiovascular

This research project will test a new method for predicting and optimizing outcomes of CRT in patients with dyssynchronous heart failure by using machine learning algorithms trained with patient-derived computational models. This project will validate the ability of our patient-specific technology to predict and optimize CRT outcomes in dyssynchronous heart failure patients, using sample sizes large enough to assess the statistical utility of these technologies.

Dyssynchronous heart failure


Andrew McCulloch
UCSD

HEAL – High Efficiency Artificial Lung

Device Respiratory

Extracorporeal membrane oxygenation (ECMO) is the last line of therapy for patients who have acute respiratory failure. It remains a high-risk device with high rates of complications, many of which are related to the high levels of systemic anticoagulation that is needed to prevent membrane fouling and clot development. By re-designing the membrane oxygenator using flat plates of micron-thin films of a gas permeable polymer supported by silicon micropore membranes, this project aims to improve the hemocompatibility of ECMO systems.

Acute respiratory failure


Shuvo Roy
UCSF

Inhibition of Abnormal Airway Smooth Muscle Contraction by Inhibitors of the α5β1 Integrin

Therapeutic Respiratory

Exaggerated airway narrowing, caused by contraction of airway smooth muscle, is a central feature in all patients with asthma, so better therapies targeting smooth muscle contraction are a large unmet medical need. We recently identified a pathway that is required for maximal force generation – tethering of airway smooth muscle cells to extracellular matrix proteins, which is mediated by one or more integrins. We are developing potent and specific small molecule inhibitors of the identified integrin(s) and evaluating their activities in vitro and in vivo. Such compounds hold great promise to meet the unmet medical need of treating airway narrowing and disability in patients with severe asthma who are refractory to current therapies.

Asthma


Dean Sheppard
UCSF

Fall 2015 NHLBI Awardees

Title Type Disease Area Description Indication PI

Lung Assist Device

Device Respiratory

Patients with acute lung failure who are refractory to mechanical ventilation have poor prognosis and utilize significant healthcare resources. Veno-venous Extra-Corporeal Membrane Oxygenation (vv-ECMO) is being increasingly used to salvage such patients, as accumulating data indicate that it is effective and may improve survival. However, the currently used vv-ECMO catheter has two major shortcomings that render it subject to positional changes and re-circulation of oxygenated blood, thereby affecting its efficiency. This project will develop a newly designed/improved catheter system for patients in respiratory failure in need of vv-ECMO.

Acute lung failure


Abbas Ardehali
UCLA

Preclinical and Clinical Studies of a Novel Read-Through Drug Capable of Restoring Cardiac and Muscle Function in Duchenne Patients

Therapeutic Cardiovascular

Duchenne muscular dystrophy (DMD) is the most severe of the neuromuscular disorders and affects 1 in 3500 newborn males. Approximately 13% of the mutations that cause DMD are nonsense mutations that lead to lack of dystrophin. The affects skeletal and cardiac muscles and is characterized by progressively loss of ambulation and premature death by cardiac or respiratory failure by the age of 30. Pulmonary symptoms also develop, such as shortness of breath and fluid accumulation or congestion in the lungs. This project will focus at developing and optimizing a drug capable of suppressing nonsense mutations and restore normal, full-length dystrophin expression. The same drug could also be used to treat virtually any genetic disease known to be caused by nonsense mutations (30% of the genetic disorders known to date).

Duchenne muscular dystrophy


Carmen Bertoni
UCLA

Video-Guided Chest Tube Insertion System

Device

Respiratory

Pleural chest tube placement performed routinely for fluid and/or air collection inside the chest can have significant complications and even result in patient deaths. This project will develop a video-guided device that provides physicians with visual aid during the chest tube insertion process, greatly reducing the risk of pneumothorax.

Chest tube insertion


Robert Cameron
UCLA

Hydrogel Device for Preventing Cardiac Adhesions Post-Cardiothoracic Surgery

Device Cardiovascular

Two main approaches exist for reducing or attempting to prevent cardiac adhesions: pharmacological therapy and physical barriers. Drugs that prevent or reverse adhesion processes disrupt biochemical pathways of inflammation and fibrin deposition. Unfortunately, these processes are also vital for wound healing. We propose a new approach to prevent postsurgical cardiac adhesions using rapidly forming poly(ethylene glycol) (PEG) hydrogels that are cross-linked by oxime bonds. As part of this proposal, we will demonstrate proof-of-principle for using the PEG oxime system to prevent cardiac adhesions in a rat cardiac surgery model.

Cardiac adhesions post-cardiothoracic surgery


Karen Christman
UCSD

Detection of Thrombin Generation for Acute MI Monitoring

Diagnostic Cardiovascular

Current standard of care for patients with chest pain and suspected acute coronary syndromes (ACS) involves considerable observation and extensive clinical reassessment of serum cardiac biomarkers for patients with intermediate risk. For safety reasons, few patients with an atypical presentation for ACS are rapidly discharged from the cardiac observation units (COUs). Physicians lack a tool that can quickly and accurately stratify risk and rule out ischemic cardiac chest pain. CardioPaint©, a non-invasive diagnostic tool for ruling- out ischemic heart chest pain from intermediate-risk patients admitted in COUs with suspected ACS for safe discharge, and rule-in for further and more effective intervention. CardioPaint© is a peptide-based technology activated by thrombin at sites of blood coagulation for imaging and detection of blood clots.

Acute coronary syndrome diagnostic


Charles Craik
UCSF

Thiolsaccharides as Novel Mucolytics for Lung Disease

Therapeutic Respiratory

This program is to develop a novel mucolytic treatment for mucus pathology in airway disease. Highly elastic mucus is difficult to clear and it results in airflow obstruction and airway infection, but there are currently no mucolytic drugs that can be given to patients by hand held inhaler. We recently discovered a mechanism of oxidant-induced increases in mucus elasticity that identifies excessive numbers of mucin disulfide bonds as a therapeutic target in stiff mucus gels. We are optimizing a series of inhaled mucolytics for Cystic Fibrosis, COPD and asthma.

Mucus disease of the lung (cystic fibrosis, COPD, asthma)


John Fahy
UCSF

A Bio-Inspired Transcatheter Mitral Valve

Device Cardiovascular

This proposed project will develop and test the first transcatheter bileaflet mitral valve with dynamic annulus, and its delivery system for transapical implantation. This bio-inspired mitral valve system will offer most of the advantages that a native bileaflet mitral with dynamic annulus has to offer for left ventricular function.

Heart valve disease


Arash Kheradvar
UC Irvine

Optical Platform for Rapid High-Throughput Screening of Cellular Mechanotransduction

Tool Cardiovascular

The initiation and/or progression of numerous pathologies has been linked to the dysregulation of cellular mechanotransduction. These pathologies include arteriosclerosis, hypertension, cardiomyopathy, and asthma which are relevant to the mission of NHLBI. We aim to develop and deploy a novel high-throughput screening (HTS) technology, that is compatible with standard image cytometry based HTS platforms, to screen for the efficacy of compounds to modulate cellular mechanotransduction processes in 2D cell cultures. Our objective is to use our technology to identify drugs that display the ability to modulate mechanosignaling as opposed to biochemical activity alone.

Arteriosclerosis, hypertension


Vasan Venugopalan
UC Irvine

Fall 2015 NIDA Awardees

Title Type Disease Area Description Indication PI

Noncrushable Pills for Prevention of Opioid Abuse

Therapeutic

Technologies or formulations to improve medication delivery and/or to deter drug abuse

Drugs like oxycodone are misused by crushing or liquefying pills for immediate dosage, causing a euphoria, which perpetuates abuse. Few robust abuse deterrent formulations are currently FDA approved. The proposed research prevents illegal use of such prescription drugs by encapsulating the drug within a biodegradable elastomer that is unable to be crushed or liquefied and will also be stable to microwaving and freezing, which many current formulations are not. The drug will only be released in the stomachs of patients who take the pills as intended.

Prevention of illegal use of prescription drugs


Heather Maynard
UCLA

Peripherally Restricted Cannabinoids for Chronic Pain

Therapeutic

Discovery and development of medications for the treatment of SUDs stemming from tobacco, cannabis, cocaine, methamphetamine, heroin, or prescription opiate use

Chronic pain represents a major socioeconomic and clinical challenge, in part because even the most efficacious of the currently available remedies are limited by their side effects. We developed synthetic peripherally-restricted cannabinoids (PRCBs) that don’t cross the blood-brain barrier, thereby providing pain relief without the side effects associated with central nervous system (CNS) cannabinoid receptor activation. These PRCBs are the first in their class to exhibit potent and repeated suppression of chronic pain symptoms, without development of tolerance, and with a complete lack of CNS-mediated side effects. Their effectiveness was demonstrated in widely used rodent models of chronic pain induced by peripheral nerve injury, burn injury, or chemotherapeutic drugs, and in cancer pain, where PRCBs also showed anti-tumor properties. Clinical implementation of PRCBs for treatment of targeted patient populations could provide relief of their chronic pain and suffering without affecting mental acuity, motor coordination, or memory. This project aims to conduct several crucial investigational new drug enabling studies including FDA-compliant assessment of safety pharmacology and toxicology, as a prerequisite to clinical implementation of PRCBs.

Chronic pain


Igor Spigelman
UCLA

Spring 2015 NHLBI Awardees

Title Type Disease Area Description Indication PI

Continuous Lactate Monitor for Early Indication of Resuscitation in Trauma and Sepsis

Device Blood

High mortality rates continue to persist in many patients with critical conditions such as sepsis, and trauma. Treatment in these cases is often aimed at stabilizing patient parameters such as vital signs. However, by the time these parameters change, it is often too late to intervene effectively. A compendium of evidence over the last few decades has shown that lactate concentration is one of the most powerful early predictors of outcome in many critical conditions, and that lactate concentration can be used to improve patient survival by directing therapy more effectively. Lactate-guided therapy is difficult or impossible to utilize in clinical practice however because current technologies allow only intermittent lactate measurements, thus failing to provide adequate and timely information about lactate changes. As such, a continuous measurement of lactate is desired to provide real-time lactate concentration. This project advances the development of our technology that will provide hands-free continuous lactate monitoring.

Lactate monitoring


Elliot Botvinick
UC Irvine

Nano-Engineered, Non-Thrombolytic Small Diameter Synthetic Vascular Grafts

Device Cardiovascular

We are developing non-thrombogenic small caliber synthetic vascular graft comprising nano-engineered surfaces. This development will allow us to significantly decrease complications associated with synthetic vascular grafts, thereby increasing patient quality of life, while at the same time contributing to a reduction in healthcare costs.

Thrombosis


Tejal Desai
UCSF

Development of a Self-Regenerative Hybrid Heart Valve

Device

Cardiovascular

This research aims to develop and test the first hybrid tissue-engineered heart valve. The hybrid heart valve leaflets are composed of a super-thin mesh of Nitinol that is tightly enclosed by multiple layers of patient’s own cells making a living implant possible within the heart.

Heart valve disease


Arash Kheradvar
UC Irvine

Gene-modified Mesenchymal Stem (stromal) Cells for Treatment of the Acute Respiratory Distress Syndrome

Therapeutic Respiratory

The acute respiratory distress syndrome (ARDS) is a major cause of morbidity and mortality in critically ill patients. This project is designed to develop a novel therapeutic based on enriched conditioned media from gene modified human bone marrow derived mesenchymal stem cells (MSC). There is an ongoing phase 2 clinical trial of MSCs for ARDS, but experimental data indicates that the conditioned media of MSC may be effective also. This project will enrich the conditioned media with transfection into MSCs of three genes that appear to be responsible for much of the therapeutic efficacy of MSCs themselves. The efficacy of the cell-free conditioned media will be tested in both in vitro and in vivo models.

Acute Respiratory Distress Syndrome (ARDS)


Michael Matthay
UCSF

2014 NHLBI Awardees

Title Type Disease Area Description Indication PI

Clinical Validation of an Unbiased Next-Generation Sequencing Diagnostic Assay for Pneumonia in a CLIA-Certified Laboratory

Diagnostic

Respiratory

More than 30% of cases of pneumonia in hospitalized patients remain undiagnosed despite extensive conventional testing. Failure to diagnose these serious infections in the timely fashion leads to ongoing nosocomial transmission and increased mortality. This project is focused upon the development of a rapid unbiased assay for diagnosis of pneumonia in a CLIA certified facility. The data will also be analyzed to identify all of the pathogens. As such it will enable appropriate treatment decisions and further understanding of pathogen etiology in pneumonia.

Pulmonary microbiome detection


Charles Chiu
UCSF

Erythroferrone Antibodies and Assays to Support Drug Development for Anemia and Iron Disorders

Combination Blood

The project is focused on the development of antibodies against erythroferrone, a newly discovered regulator of iron metabolism. These antibodies will have likely utility for the differential diagnosis of anemias and iron overload disorders, and as companion diagnostics for new agonists and antagonists of the erythroferrone pathway that are under development.

Anemias and iron overload disorders. Companion diagnostics for therapeutics directed at the erythroferrone pathway.


Tomas Ganz
UCLA

A Nanophotonic Platform for Rapid and PCR-free Detection of Bacterial and Fungal
Infection

Combination Cardiovascular

This projects features the use of an ultrasensitive nanophotonic detection device for the detection of fluorescence that is a marker for the DNA of bacterial pathogens that lead to infections in humans. The desired product will be a "point-of-care" DNA diagnostic platform based on optical amplification - without requiring a polymerase chain reaction - that will allow the implementation of protein and DNA assays at a patient's bedside, in a matter of minutes.

Multiple bacterial and fungal infection detection


Ian Kennedy
UC Davis

Selective Targeting of TGF-ß Activation for Airway Remodeling with Engineered Monoclonal Antibodies

Therapeutic Respiratory

Chronic obstructive pulmonary disease (COPD) is now the third leading cause of death in the United States (2) Current treatments provide incremental palliative benefit in COPD patients. There are currently no therapeutics which have been demonstrated to change the course of the disease. This project focuses on developing diagnostic and therapeutic antibodies which target TGFb mediated inflammation and fibrosis in COPD. These will be used to identify the sub-populations of COPD patients where modification of TGFb activation has the greatest potential impact and to develop a TGFb activation targeted therapeutic.

Pulmonary diseases such as COPD and IPF


Stephen Nishimura
UCSF

Questions?

Click the links below to
contact your Research Navigator.


Join our Mailing List 
Follow us on Twitter