Arizona State University with Immunoshield Therapeutics: High-Throughput Biomanufacturing of Encapsulated Cell Products

Cell therapies are a new type of treatment with the potential to functionally cure a range of chronic diseases. However, allogeneic cell therapies require immune suppression, presenting serious acute risks to the patient, so that only a small fraction of patients currently qualify for cell therapy to treat their disease. The team’s method maximizes patient safety by containing cell therapies within an encapsulation device that can (1) reduce or eliminate the need for immune suppression and (2) enable the retrieval of cell therapies in the case of adverse events. This method has a distinct advantage in that it enables scalable, high-throughput biomanufacturing of encapsulated-cell products; this advancement will enable the production of sufficient doses to treat large numbers of patients. Principal Investigator: Jessica Weaver, Ph.D.

Arizona State University with Mayo Clinic: HistaHeal: Bioactive Dressing for Diabetic Wounds

The research team has developed a bioactive dressing, HistaHeal, to aid in healing complex wounds, including diabetic wounds. More than 6 million chronic and complex wound cases incur over $20 billion in health-care costs in the United States annually; diabetes delays repair and leads to chronic ulcers with high morbidity and mortality. Using biomaterial engineering and biomimetic cargo delivery, HistaHeal stimulates multiple reparative wound-healing signaling pathways to accelerate wound closure and improved functional recovery of skin. Combining a safe, naturally derived biopolymer with an endogenous pro-repair small molecule or specific receptor-targeting analogs, HistaHeal promotes rapid re-epithelialization of wounds to accelerate closure, while stimulating a pro-healing immune signature. Principal Investigator: Jordan R. Yaron, Ph.D.

Arizona State University with Mayo Clinic: A Point-of-Care Test for the Rapid Diagnosis of Valley Fever

In parts of central and southern Arizona, and in California’s Central Valley, up to 30% of patients with pneumonia have valley fever, a respiratory disease caused by inhalation of Coccidioides fungus spores. Unfortunately, it is difficult to distinguish valley fever from other pneumonia-causing viral and bacterial infections. Without a rapid, sensitive, specific test, an urgent-care physician is unlikely to order a valley fever test, because results may not be available until four days after the patient has been discharged. This team’s rapid test provides a clinically actionable answer in 10 minutes with a single drop of blood. Compared to the only other commercially available test for valley fever, this team’s rapid test is faster, quantifiable, more accurate, can use whole blood, and is amenable to consistent, high-quality production. Principal Investigator: Douglas Lake, Ph.D.

Barrow Neurological Institute: Neurostimulator Device for Assessment of Consciousness

Successful clinical management of critically ill patients with neurologic and traumatic pathologies or injuries centers on understanding the functional status of their central nervous system; level of consciousness is the most important clinical indicator of a patient’s neurologic status, and the Glasgow Coma Scale (GCS) is the standard examination of level of consciousness for clinical practice. Widespread use of the GCS has led to significant improvements in patient management, and the GCS has been incorporated into many widely used clinical decision-making algorithms, but it has several problems that limit its potential and have caused some experts to question its use. This team is developing a new device and methodology for the GCS that will not rely on mechanical pain stimulation. Principal Investigator: Brandon Fox, M.D.

Grand Canyon University: Sepsis Dx: A Septic Shock Screening Device

Sepsis—wherein serious organ/tissue failure is caused by a systemic inflammatory response from either a viral or bacterial infection—is typically detected via fever, breathing, heart rate, and lethargy. To decrease mortality rate and reduce drug resistance, sepsis needs to be diagnosed as early as possible following infection. To accomplish this, a simultaneous sepsis biosensor sensing system will be developed to monitor three biomarkers indicating the presence of sepsis, enabling clinicians to quickly diagnose all cases of sepsis regardless of origin and thus decrease the mortality rate. The goal of this project is development of a multi-biosensor, wearable device to diagnose sepsis more rapidly. Principal Investigator: Jeff La Belle, Ph.D.

University of Arizona: Development of a Novel Therapy to Treat COPD

Chronic obstructive pulmonary disease (COPD), the third leading cause of death worldwide, is a group of lung diseases, including emphysema and chronic bronchitis, characterized by recurrent infections and inflammation. Recent studies have reported decreased levels of club cell secretory protein (CC16) in COPD patients, and this team has found that CC16 delivered into the bloodstream rescues lung function, limits immune-cell migration into the lungs, and enhances epithelial host responses to pathogens; it protects from COPD as an anti-inflammatory protein in circulation and by promoting secretion of defensive factors in the respiratory epithelia to aid in pathogen clearance. The team is developing CC16-derived peptidomimetics and is working to enhance solubility, efficacy, and stability, while minimizing size and toxicity. Principal Investigator: Julie Ledford, Ph.D.

University of Arizona: Targeting TDP–43 for Neurodegenerative Diseases

TDP–43 (transactive response DNA binding protein of 43 kDa) is the common hallmark disease protein for various major neurodegenerative diseases. Mitochondria are closely linked to neurodegeneration, and have recently emerged as a critical target of TDP–43. The project team has reported a novel peptide-based TDP–43 inhibitor named “PM1” that was specifically designed to disrupt the association of TDP–43 with mitochondria and has been shown to prevent and even reverse disease progression in different neurodegeneration models. The promising prior work warrants further development and optimization of this novel TDP–43 inhibitor. The work proposed in this project will enable the project team to commercialize TDP–43 inhibitors as a common disease-modifying care for neurodegenerative diseases. Principal Investigator: Xinglong Wang, Ph.D.

University of Arizona with Banner University Medical Center: Gynecologic Cancer and Disease Diagnostic with At-Home Test Collection

Diagnostic options for uterine diseases are limited to biopsy or suboptimal imaging. Biopsy can cause anxiety, physical discomfort, and pain, and some uterine conditions, such as adenomyosis, can only be diagnosed after surgical removal of the uterus; this invasive diagnostic approach creates a barrier for early detection and treatment. This project team has previously demonstrated that minimally invasive cervicovaginal lavage (CVL) sampling allows detection of biomarkers for a range of gynecologic conditions and that these biomarkers can predict disease severity. The team’s ultimate goal is to create an at-home test for gynecologic diseases, which will benefit women by improving detection and consequently decreasing health inequities throughout Arizona and including underserved and rural populations. Principal Investigator: Melissa Herbst-Kralovetz, Ph.D.

University of Arizona with Banner University Medical Center: A Targeted Therapy for Intracranial Hemorrhage

Bleeding in the brain, or intracranial hemorrhage (ICH), is a devastating medical condition, and no medical therapy improves outcomes. Primary ICH affects 5.3 million people worldwide each year, 60% of patients die, and most survivors are left disabled. Data suggests that matrix metalloproteinase–9 (MMP–9) worsens ICH and contributes to brain damage. The project team is already developing an MMP–9 inhibitor that markedly decreases brain bleeding in patients with another condition, ischemic stroke. For this project, the team will test whether this MMP–9i can also reduce bleeding in ICH. Data that MMP–9 inhibition is effective for ICH would provide the rationale to support development of this MMP–9i to treat this devastating disease. Principal Investigator: Guy Reed, M.D.

University of Arizona with Banner University Medical Center: Transcranial Acoustoelectric Imaging of Deep Brain Stimulation Currents

Deep brain stimulation (DBS) is used to alleviate symptoms of Essential Tremor and Parkinson’s Disease, with increasing demand for treating conditions like depression and Alzheimer’s disease. The effectiveness and failure rate of DBS strongly depends on location of the leads and specific parameters for stimulation; however, there remains an unmet clinical need for an in vivo method to safely and noninvasively pinpoint electrode contacts to guide placement of the DBS device during insertion, image current flow during behavioral assessment and setting stimulation patterns, and long-term monitoring of device integrity after implant. This project would devise a real-time transcranial acoustoelectric brain imaging (tABI) system capable of remotely mapping DBS currents at the millimeter scale. Principal Investigator: Russell Witte, Ph.D.

University of Arizona with Banner University Medical Center and M.D. Anderson Cancer Center: Neuroendocrine Tumor Surgical Localization

Gastroenteropancreatic neuroendocrine tumors (GEP-NETs) are the second most common digestive cancer and would greatly benefit from next-generation intraoperative imaging systems to enable accurate localization and margin definition. The key to improving GEP-NET resection is to develop a laparoscopic imager for minimally invasive surgery that enables wide-area tumor localization and high-resolution inspection for margin definition. This team has worked toward implementing a contrast agent for GEP-NETs for wide-field fluorescence imaging and has shown that multiphoton microscopy can differentiate clear margins between tumor and normal tissue. The team has designed the architecture for a laparoscope implementing this technology for GEP-NET resection and the next step is to build and test the device. Principal Investigator: Travis Sawyer, Ph.D.

University of Arizona with Innoventyx LLC: Novel Approach to Eliminate Opioid Addiction in Pain Management

Opioid analgesics (OA), are the most efficacious drugs for the management of chronic pain. In 2020, about 143 million opioid prescriptions were dispensed in the United States; unfortunately, 21–29% of patients with chronic pain misuse prescribed OA, and 8–12% develop opioid addiction (so-called Opioid Use Disorder or OUD). To prevent drug addiction in pain management, the project team proposes to use novel first-in-class drug candidates that, in combination with OA, can control/prevent addiction while analgesic properties remain unchanged. The team has developed a library of compounds that target key biological activities involved in pain and OUD. The project team’s front-runner drug candidate prevents development of addiction when used in combination with morphine, while showing improved analgesic effects. Principal Investigator: John Streicher, Ph.D.

Arizona State University: Target to Trial Rapid Immunotherapy Development for West Nile Virus

There are currently no specific treatments for West Nile or related diseases and no therapies at any clinical phase of the development timeline. This project will fund an accelerated platform for biologic drug development, operating at 100 times the scale for a fraction of the cost of current methods, which could make a treatment for West Nile feasible and set a new standard of development and affordability for biologic therapies globally.

Arizona State University with Barrow Neurological Institute and University of Arizona College of Medicine-Phoenix: Biomarkers for Clinical Diagnosis of ALS Patients

The successful completion of the proposed work will enable translation of biomarkers to diagnose ALS patients in the early stage of their disease course, surpassing current capabilities and offering the first means of prognosis. The lack of clinical options has led to delayed diagnosis for upwards of a year. This new approach introduces, for the first time, an effective measure for establishing a clinical diagnosis for ALS, which could improve therapeutic efficacy.

Arizona State University with Mayo Clinic Arizona: Tattoos for Endoscopic Imaging

Effective surgical intervention in the gastrointestinal tract requires easy identification and visualization of diseased regions. This project develops a new generation of endoscopic tattoo inks that demonstrate precise spot sizes, minimal inflammation, high retention, and low loss from target tissue, such as colon. It possesses the capability of visualization by multiple clinical imaging technologies, including magnetic resonance imaging.

Northern Arizona University with Phoenix Children’s Hospital: Wearable Robotic Gait Therapy for At-Home Mobility Care

The project aims to develop, test, and commercialize the world’s first pediatric wearable Robotic Ankle Assist Device for children with cerebral palsy. The researchers will adopt a user-centric design approach to create a reliable, effective and safe assistive device suitable for personal use by adolescents and adults, leading to increased levels of activity. Current approaches for treating cerebral palsy do not improve mobility over time, and many children lose the ability to walk as adults.

Translational Genomics Research Institute: Development and Commercialization of a Blood-Based Assay for Disease Monitoring in Patients with Pancreatic Cancer

Roughly 18% of pancreatic cancer patients lack a suitable blood-based marker to identify whether their current treatment is working or to track when effective treatments stop working. The extracellular-vesicle based marker the research team is developing could be used for tracking all pancreatic cancer patients. This will be a valuable tool for those patients without elevated levels of CA19-9 and could ultimately be a more accurate marker for disease burden and clinical benefit.

University of Arizona: Ruthenium-Based Antivenom Development

This project hopes to develop a universal antivenom and create a commercial medicinal product. Most snake antivenoms are polyclonal antibodies, are specific to only one venom, and require the venom itself to manufacture it. The symptoms of snake bite are caused by the myriad of enzymes and other substances contained in the snake venom. This laboratory has demonstrated that a novel family of chemicals—a universal antivenom—are capable of inhibiting snake venom by binding to key areas of these enzymes.

University of Arizona with Banner Health: Virtual Portfolio for Skull Based Surgical Training

This project team has recently developed a mixed-reality neurorhinologic (MR-NRS) surgical simulator and the teaching steps and software to train residents and fellows. The goal of the project is to develop a library of patient-specific skull base tumors, in which trainees can utilize the MR-NRS simulator to learn about the critical anatomical structures of the case, interact in an immersive environment with the surgical instruments and tools, and test educational methods to prepare for these cases and be exposed to complications prior to encountering skull-base surgeries in the real world.

University of Arizona with Carondelet Neurological Institute and University of Pittsburgh: Improved Stroke Management through Medical Imaging and Artificial Intelligence

A major setback in acquiring CT perfusion scans in stroke patients is the substantial gap in the availability of equipment and facilities, which are not available at smaller hospitals and clinics. The project team will build and validate a hybrid imaging and artificial-intelligence algorithm to estimate regional brain perfusion in stroke patients and provide tissue viability measures. The technology will reduce time to diagnosis and reduce rate of patient transfers to comprehensive stroke centers for rural and community hospitals.

University of Arizona with Florida International University: Oxytocin Analgesics Without Side Effects for Opioid Use Disorder

The introduction of oxytocin (OT) glycosides into clinical use would allow for the treatment of moderate-to-severe pain without use of opioids and their undesired side effects. This project team proposes that the OT-based drugs can be provided to a patient following dental procedures and/or outpatient surgical procedures in the form of an intranasal inhaler that could be administered as needed to control pain. Patients treated with OT-based drugs are not expected to engage in drug-seeking behavior following their use.

University of Arizona with New York University: GABA Transaminase Inhibitors for Type 2 Diabetes

Current Type 2 diabetes therapies maintain glycemic control in only 36% of patients. Fatty liver is associated with the severity of diabetes and pre-diabetes. The investigators have worked to understand how fatty liver communicates with the rest of the body to cause insulin resistance and elevated blood insulin concentrations and have shown that fat accumulation in the liver increases liver GABA release. By targeting the cause of elevated blood glucose, insulin, and insulin resistance, the project hopes to develop two highly effective, specific, novel GABA-T inhibitors to treat Type 2 diabetes.

Arizona State University with Barrow Neurological Institute:  Minimally Invasive Neuromodulation of Occipital Nerve to Mitigate Chronic Migraine

The project seeks to develop a portable, hand-held, neurostimulation system for a patient to use for a few minutes at a time to mitigate pain during an episode of chronic migraine. The injectable neurostimulation technique will provide the spatial precision of implanted microscale leads. This could bring relief to 1.4-2.2% of the world’s population that is impacted by chronic migraine and suffer with migraines about 15 or more days per month.

Arizona State University with Mayo Clinic Arizona: FlexBioTech Fluorescence-Based Testing for Point of Need Diagnostics

The project will adapt the current implementation of the ASU COVID-19 diagnostic system to a point-of-need diagnostic to fulfill the need of remote testing with high sensitivity. The diagnostic, which uses a robust, multiplexed, quantitative, pocket-size system, could be used for early detection of COVID-19 in developing countries. The testing relies on smartphones for the cloud storage of data and computational resources for algorithms.

Northern Arizona University with Barrow Neurological Institute: Development of a Novel Balloon-Stent Device to Improve the Embolization of Aneurysms

The project’s focus is to develop, refine, and validate a novel medical device to treat aneurysms in the brain. The prototype could be used in conjunction with current available devices and would minimize the risk of stroke effects in the short-term, and aneurysm rupture in the long-term. The balloon-stent device would provide surgeons more time to deploy embolics without blood flow arrest while obtaining more complete aneurysm treatments.

Translational Genomics Research Institute: N-GARD: A 21^st Century Solution to Age-old Healthcare Problem – Antibiotic Resistance

The project will update a research-use-only antimicrobial resistance detection tool, N-GARD, which can detect hundreds of different causes of drug resistance in healthcare infections. The tool would then be validated for clinical use and adopted by TGen for use on patient specimens. The project is needed as personalized treatment requires that clinicians receive rapid, comprehensive information on a patient’s infection and likely response to therapy.

Translational Genomics Research Institute: Prevention of Inherited Genetic Disease using Whole Genome Sequencing

The project will develop tools needed to analyze entire genome sequences of couples to determine if they are at risk for transmitting an incurable genetic disorder if they become pregnant, define the limitations of such testing, address ethical and moral issues that might arise, explore issues of reimbursement for such tests, and also develop a consistent approach for genetic counseling of such couples.

University of Arizona: Enabling the Early Diagnosis of Chronic Lung Diseases with a Blood-Based Metabolomics Diagnostic Powered by Machine Learning

The project will develop a blood test that can diagnose chronic lung diseases at the onset of symptoms that is less invasive and costly. Today, it often takes between two and four years to make a correct diagnosis of the often-fatal lung diseases because of the non-specific symptoms. The new blood test would allow patients to learn their diagnosis within days and start therapeutic intervention when the responsiveness to treatment is still high.

University of Arizona with Banner University Medical Center -Tucson: A Microbiota-Sparing Live Biotherapeutic for C. difficile infection

The project looks to establish a novel treatment for the deadly bacterial pathogen C. difficile. C. difficile infections, or CDI, are the most common healthcare-associated infection in many hospitals and there are currently no preventive treatments or vaccines for the disease. The researchers will further study their non-antibiotic, orally palatable therapeutic, Syn-LAB, with the hope of moving the treatment into clinical development.

Arizona State University, in partnership with Mayo Clinic Arizona: Designing biomimetic fibrous scaffolds with spatially controlled mineralization for augmenting rotator-cuff repair

The project’s goal is to develop innovate tissue-engineered therapeutics for rotator-cuff repair. Rotator-cuff tears are common and re-tear rates can be as high as 90 percent. The project will develop new gradient materials that can mimic the natural gradients in the tendon-to-bone interfacial tissue and serve as a template for controlling tissue repair. The goal is for the new materials to have applications outside this project, including anterior cruciate ligament, meniscus, and other fibrous tissues.

HonorHealth Research Institute, in partnership with University of Arizona College of Medicine-Phoenix and Microsoft: Development of a virtual-reality platform to enhance patient health literacy and clinical-trials informed consent.

The project proposes a first-of-its-kind digital tool exploiting augmented-reality and virtual-reality environments, combined with novel algorithms, to allow for deeper patient engagement. The goal would be to improve health literacy for patients to make better decisions, including improving the ability to comprehend benefits, risks, and alternatives to the procedure or therapy considered. The tool would also benefit cancer patients searching for potentially life-prolonging clinical trials.

Northern Arizona University, in partnership with TGen and Los Alamos National Laboratory: Pre-clinical testing of mathematical model prediction of RAF inhibitor effects in humanized zebrafish

The emphasis for this project is treatment of melanoma, the most lethal type of skin cancer, with the hope of using the treatment approach on numerous kinase-driven cancers. Various targeted therapies have been successful for some patients with melanoma, while the same treatments given to other patients have failed. The goal is to leverage a computational pipeline that predicts therapeutic responses to novel combinations of FDA-approved drugs in cancer cell lines and in humanized zebrafish harboring melanoma skin cancer.

St. Joseph’s Hospital and Medical Center/Barrow Neurological Institute: Identification of Biomarkers for Idiopathic CIDP, CIDP with MGUS and Diabetic CIDP

The study will identify blood-based biomarkers that will enable early and effective treatments for people with chronic inflammatory demyelinating polyneuropathy, a neurological disorder, along with diabetics with CIDF. The disorder leads to progressive weakness and impaired sensory function in the legs and arms. While there is effective treatment if the disease is identified early, diagnosis can be difficult, especially if the patient is also diabetic.

St. Joseph’s Hospital and Medical Center / Barrow Neurological Institute, in partnership with Vanderbilt University and Philips Healthcare: Establishing a real-time analysis plug-in for clinical perfusion imaging

The project is developing a critical new option for brain-tumor patient management that would remove the need for surgical biopsy to confirm therapeutic response—a standard-of-care approach that increases cost and morbidity. The project hopes to establish an automated and real-time acquisition and analysis pipeline that enables true clinical translation of a perfusion-imaging protocol.

TGen, in partnership with Mayo Clinic Arizona: An innovative application for diabetes personalized care

The project aims to improve life-long patient compliance with insulin site rotation for patients with Type 1 diabetes and some patients with Type 2 diabetes. The plan is to develop an application for iOS and Android mobile platforms that employs a novel algorithm to better guide insulin site rotation, which reduces the risk of lipohypertrophy, infection, flare, skin injury, scarring, and irritation.

Translational Genomics Research Institute, in partnership with Mayo Clinic Arizona: Optimizing treatment of metastatic breast cancer through real-time disease monitoring

The project hopes to address the gap in monitoring response to treatment in patients with metastatic breast cancer, an incurable disease. Imaging is used to monitor the disease in the standard-of-care treatment, which can only be repeated at two-month intervals, leaving patients potentially exposed to ineffective therapy and delaying revised treatment plans. This proposal will use circulating tumor DNA analysis to bridge the two-month gap.

University of Arizona Department of Biomedical Engineering: A soft, battery-free, wireless, and wearable digital-health platform for continuous frailty assessment

The project will enable providers to monitor health status and diagnose, manage, and treat patients in and outside the clinic. The proposed device, which could be worn for weeks at a time by relying on wireless energy sources, will be tested on older patients who are frail. The flexible device will serve as an alternative to the current hardware for wireless data collection.

Arizona State University in partnership with Mayo Clinic Arizona: An Integrated Metagenomics and Immunoproteomics Study of the Role of Microbiome in Pouchitis Development

The project will establish an Arizona-based infrastructure to collect biobank samples to be accessed by a network of gastroenterologists, including academic and community physicians, to conduct a pilot study that would provide insight into the role of the microbiome over time, specifically as it relates to the development of ulcerative colitis, a chronic inflammatory bowel disease. The creation of the new infrastructure is expected to improve the chances of these researchers receiving NIH funding in the future.

HonorHealth Research Institute in partnership with TGen: Development of Novel Methods to rapidly credential combination therapies for incurable colorectal cancer using Next Generation Sequencing and organoid cultures from patient

The project seeks to use a patient’s tissue to find drug combinations to treat colorectal cancer. The researchers will use RNA-sequencing analysis to identify pathways and predict drug combinations specific to each colorectal cancer patient. The organoid platform will allow growth of the patient’s tumor in the lab and thus the ability to identify the best therapy for the individual patient. HonorHealth Research Institute will be working with Translational Genomics Research Institute and its certified genomic testing lab on the project.

Northern Arizona University in partnership with Mayo Clinic Arizona: Gut Microbiome Manipulation for Treatment of Asthma

This study will look to determine whether prebiotic fiber supplementation can lead to improved clinical asthma outcomes. Asthma is affected by genetic and environmental factors, which may include the Western diet that is high in sugar and saturated fats but low in fiber. The researchers’ theory is that increased fiber will lead to changes in the gut microbiome and in asthma disease outcomes.

Northern Arizona University in partnership with Yuma Regional Medical Center: Health Disparities Associated with Fungicide Exposure Among Residents of Yuma

This project will investigate health disparities associated with fungicide exposure among migrant farmworkers and other Yuma-area residents. The goal is to develop precision-medicine screening and interventions to reduce the impact of environmental contaminants in high-exposure populations. The study, using human and rodent hair samples, will examine associations between concentrations of metals used in fungicides and adverse health outcomes.

St. Joseph’s Hospital and Medical Center/Banner Neurological Institute in partnership with Banner Alzheimer’s Institute: Pituitary Adenylate Cyclase Activating Polypeptide (PACAP)

This project will test the hypothesis that significant changes in pituitary adenylate cyclase activating polypeptide (PACAP) and Sirt3 levels can be detected in early-stage Alzheimer’s disease and be used to predict progression from mild cognitive impairment to Alzheimer’s. One goal is to determine whether cerebrospinal fluid levels of PACAP and Sirt3 differ between cognitively normal patients and those with mild cognitive impairment or Alzheimer’s disease. The study could identify a biomarker and provide the foundation for early diagnosis of the disease and new therapies.

University of Arizona College of Medicine-Phoenix and College of Pharmacy-Tucson in partnership with Banner Health: Large-scale Implementation of Pharmacogenomics: Translating Genotype-Guided Warfarin Dosing from Discovery to the Bedside

This project will use a patient’s data, such as age, weight, and current medications, along with genetic data, to better predict an initial dose of warfarin. Today, the generic starting dose of warfarin results in patients being under- or overdosed, increasing the risk of blood clots and bleeding. An electronic medical record will be established so doctors across many western hospitals would be aware of the patient’s personalized warfarin dose. The study will focus on Hispanics and African Americans, who are traditionally underrepresented in warfarin testing.