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2019 Galvanizing Engineering in Medicine (GEM) Awards

UC San Diego Altman Clinical and Translational Research Institute (ACTRI) announces the selection of six physician-engineer teams as the 2019 recipients of the Galvanizing Engineering in Medicine (GEM) awards. GEM, an initiative of ACTRI and UC San Diego Institute of Engineering in Medicine (IEM), supports projects that identify clinical challenges for which engineering solutions can be developed and implemented to improve health care. It is a collaboration between ACTRI and the Institute of Engineering in Medicine (IEM). Leading this initiative are Gary S. Firestein, MD; Shu Chien, MD, PhD; and Deborah Spector, PhD. The GEM recipients and their projects are below.

Andrew Kahn

Andrew Kahn, MD
School of Medicine, Depatment of Cardiology

Juan DelAlamo

Juan DelAlamo, PhD
Jacobs School of Engineering, Department of Mechanical and Aerospace Enineering

Title: Personalized assessment of left atrial thrombosis risk by computational fluid dynamics

Atrial fibrillation (AF) is the most common cardiac arrhythmia, affecting approximately 35 million people worldwide, and is associated with the risk of blood clots forming in the left atrial appendage and traveling to the brain resulting in strokes. The risk of strokes in patients with AF can be reduced with anticoagulation medications, but these increase the risk of bleeding and current methods of deciding who should get these are not personalized and contain no information about patients' cardiac anatomy. 

The main objective of this project is to develop novel CT imaging analyses to quantify the personalized risk of LAA thrombosis in AF patients. Our scientific premise is that blood stasis is a key ingredient of thrombosis because it permits thrombogenic reactive species to interact and initiate clot formation. We will develop a computational framework to quantify left atrial blood stasis by 4D CT imaging of atrial kinetics combined with computational fluid dynamics (CFD). We will develop image processing algorithms for quantification of left atrial kinetics based on time-resolved CT scans. We will establish the relationship between 4D atrial kinetics by multi-heartbeat contrast CT and blood stasis using CFD, in order to facilitate the clinical translation of stasis mapping by CT alone. We will apply this methodology to a pilot cohort of patients with atrial fibrillation. Our translational goal is to provide clinicians with a novel image-based tool for personalized risk stratification of patients with atrial fibrillation to guide anticoagulation decisions and improve outcomes.

Robert (Chip) Schooley

Robert (Chip) Schooley, MD
School of Medicine, Department of Infectious Diseases

Nicole Steimetz

Nicole Steimetz, PhD
Jacobs School of Engineering, Department of Nanoengineering

Title: Real-time monitoring of phage therapy pharmacodynamics

Infectious diseases have become lethal again in the 21st century owing to a plethora of pathogens that have developed unparalleled resistance to antibiotics, due to the rise of multidrug-resistant (MDR) bacteria. Phage therapy has re-emerged as powerful “living therapies” to combat MDR infections. There is an urgent need for pharmacodynamic investigation, but imaging technologies that allow the dynamic, real-time imaging of infectious bacteria combat are lacking. The key challenge is that unlike conventional antibiotics, phage replicate inside the bacterial host and they produce progeny virions as long as susceptible host cells exist. Direct labeling of phage only allows monitoring the first pass administered dose, and thus is not an accurate measure of dose or pharmacodynamics. We propose principles of directed evolution to develop a tracer technology to tag both the first pass and the progeny phage, by chasing and labeling these phages in vivo.

Antonino Catanzaro

Antonino Catanzaro, MD
School of Medicine, Department of Pulmonology 

Timothy Rodwell

Timothy Rodwell, MD, PhD, MPH
School of Medicine, Department of Public Health & Preventative Medicine

Joseph Wang

Joseph Wang, DSc
Jacobs School of Engineering, Department of Nanoengineering

Title: Point-of-Care Electrochemical Immunoassay for TB Diagnosis

Despite effective treatment regimens, tuberculosis (TB) remains a significant public health threat, causing more than 10 million new cases of active disease and over a million deaths annually—making it the number one infectious disease killer worldwide. Additionally, between one quarter and one third of the world’s population has already been infected with dormant Mycobacterium tuberculosis (Mtb) bacteria. And, although these latently infected individuals are not sick and cannot transmit the disease, they do have the potential to re-activate to an infectious state. Given that the highest TB burdens are in regions with the least resources to deal with the disease, the ideal diagnostic for TB is one that is based on a minimally- or non-invasive clinical sample, can distinguish active disease from latent infection, is rapid (<2 hours), costs <1USD/test and can be performed by non-skilled personnel anywhere in the world. Currently however, no such diagnostic test exists for detecting active TB disease. The consequence of this lack of a rapid, affordable, and accurate point-of-care test for TB is an inefficient healthcare environment that amplifies transmission, fuels drug resistance, and jeopardizes global TB control.

Global pulmonary TB diagnosis is primarily dependent on sputum smear microscopy, despite well-documented studies showing microscopy has limited sensitivity (40-60%) in high burden settings, a false-positive rate of ~40% in low burden settings and requires a sputum sample which is difficult to produce in children and patients with HIV. The only widely available alternatives are also dependent on sputum samples: 1) Sputum culture, is highly sensitive/specific, but slow (weeks), expensive, and requires centralized facilities; and 2) Nucleic Acid Amplification Tests e.g. Cepheid GeneXpert, which are rapid, have good sensitivity/specificity, but are costly (>10 USD/test) and require high-level facilities to function reliably.

The presence of early secreted antigenic target 6-kDa protein (ESAT-6) and 10-kDa culture filtrate protein (CFP-10) in clinical samples indicates Mtb replication and offers an attractive target for diagnosing active TB disease. These proteins have been previously detected in TB patient serum, cerebral spinal fluid, and urine in physiologic concentrations, but the technologies required to detect them cannot be implemented as low-cost, point-of-care tests and require invasive sampling. The objective of this proposal is to develop a novel disposable, screen-printed carbon electrode sensing chip to capture both ESAT-6 and CFP-10 antigens found in saliva of TB patients, by adapting a proprietary sandwich immunoassay technology developed by the Wang laboratory at UCSD. We propose to achieve this objective by 1) adapting and optimizing an existing sandwich immunoassay dual biomarker prototype to detect Mtb antigens ESAT-6 and CFP-10 in an aqueous solution and sterile saliva matrix, 2) establishing the limit of detection for the optimized prototype using contrived samples of commercially obtained ESAT-6 and CFP-10 antigen in sterile saliva matrix, and 3) characterizing the analytical sensitivity and specificity of the optimized prototype assay using clinical samples collected from pulmonary TB patients with positive TB cultures and patients without a TB diagnosis. Successful development and optimization of this proposed assay with an estimated cost of goods <1USD/test is feasible, achievable, and has the potential to transform TB diagnosis globally.

Pranav Garimella

Pranav Garimella, MBBS, MPH, FASN
School of Medicine, Department of Nephrology

Jesse Jokerst

Jesse Jokerst, PhD
Jacobs School of Engineering, Department of Nanoengineering

Title: Understanding of the Pathophysiology of Wounds from peripheral artery disease (PAD) in Chronic kidney disease (CKD)

Chronic wounds from peripheral artery disease (PAD) and diabetic foot ulcers are a major health concern especially in persons with chronic kidney disease (CKD). Tools to diagnose these wounds before they develop or evaluate deep tissue response to therapy have remained elusive. Currently, visual inspection remains the standard of care for detection early stage ulcers but is of limited utility. Thus, tools to map changes in tissue physiology that precede ulcers could be revolutionary to the diagnosis and treatment of chronic wounds.  This project will use photoacoustic ultrasound to create a detailed map of the tissue physiology at the wound site or site of a potential wound. This information can identify the site needing treatment or how a site is responding to treatment. Our preliminary data used a prototype photoacoustic system to detect pressure ulcers before they erupted in mice. We believe that this approach can be expanded to have value in diabetic foot ulcers even in humans because signals in photoacoustic ultrasound are based on changes in tissue optical absorption from hemoglobin, and these changes will be the same both in pressure and diabetic foot ulcers. In addition to offering three-dimensional imaging, our photoacoustics approach will map and measure the extent of dysregulation through the first 5 cm of tissue. In the future, this will be particularly useful in monitoring a treatment response because areas of low response can be prioritized for additional treatment. Our overarching hypothesis is that the use of photoacoustic ultrasound will advance our understanding of the pathophysiology of chronic wounds and provide the community a tool to detect ulcers before they are visually apparent.

Andrew Vahabzadeh-Hagh

Andrew Vahabzadeh-Hagh, MD
School of Medicine, Department of

Karen Christman

Karen Christman, PhD
Jacobs School of Engineering, Department of Bioengineering

Title: Development of an Injectable Biomaterial for Dysphagia Rehabilitation

Treatment of head and neck cancer can result in a debilitating loss of tongue function. This can lead to disabling dysarthria, dysphagia, and life-threatening aspiration. Current treatment of tongue dysfunction includes swallow therapy aimed at maintaining tongue function during and after cancer treatment. Although of great importance, such treatment is unable to restore tongue function once it is lost. Innovative treatments for this disabling problem are needed. A regenerative medicine approach holds promise for treating tongue atrophy and fibrosis. Here we aim to test the feasibility and effects of a novel injectable biomaterial scaffold derived from decellularized muscle extracellular matrix that encourages skeletal muscle regeneration in a rat tongue scar model. We hypothesize that the injection of this biomaterial will promote muscle engraftment, growth, tongue volume, bulk and function. In establishing this application and proof of concept we hope to fast track its utilization in patient care to start improving the quality of these patient’s lives as soon as possible.

Kevin King

Kevin King, MD, PhD
Jacobs School of Engineering, Department of Bioengineering

Todd Coleman

Todd Coleman, PhD
Jacobs School of Engineering, Department of Bioengineering

Title: A Demixable Adherence-independent Non-contact In-bed Sensor for Heart Failure Biomarkers

The 30-day hospital readmission rate in the U.S. exceeds 3 million patients per year with cost estimates exceeding $40B. More than 10% of these hospitalizations are considered preventable. Chronic and recurrent cardiopulmonary diseases (heart failure, pneumonia, COPD, cardiac dysrhythmias, acute myocardial infarction) are among the most common causes of rehospitalization. Heart failure alone affects more than 6 million US patients, is responsible for >1 million hospitalizations annually, and is associated with remarkably high hospital readmission rates (~25% at 30 days; ~50% by 6 months). Intense focus has centered on improving outpatient disease management using remote monitoring during vulnerable periods (immediately after hospital discharge) and in vulnerable underserved populations. Despite its promise, the utility of remote health monitoring has been limited by lack of adherence to patient self-measurement and data transmission. Even implantable devices often require patient-initiated data transmission. To address this important clinical problem, we are developing a novel adherence-independent home monitoring technology in which dynamic force sensors are placed beneath the legs of a person’s home bed. By measuring the dynamics of individual sensor force across time and analyzing the resulting signals, we will noninvasively and in a fully adherence-independent manner, perform in-home monitoring of weight and cardiopulmonary clinical biomarkersThe current GEM proposal focuses on development of algorithms to demix signals from two individuals who share a bed. By developing hardware and software for adherence-independent physiologic sensing in the comfort of one’s home bed, even when it is shared with a partner or pet, we hope to learn the signatures of impending hospitalizations and use them to optimize care.