SPUR 2021 Projects: Medicine

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SPUR projects are listed in alphabetical order by faculty mentor last name.

Biomedical Informatics | School of Medicine


EXTRACTING THE TEMPORAL PATTERNS OF MULTIPLE SEPSIS OUTCOMES IN THE INTENSIVE CARE UNIT

Samir Abdelrahman, Assistant Professor

Several types of patients are hospitalized in intensive care units (ICU), such as patients with multiple outcomes of sepsis (i.e., sepsis, severe sepsis, sepsis shock, and organ failure) in many cases, multiple sepsis outcomes (i.e., the sequential multiple onsets of these outcomes and mortality). One-third of ICU patients suffer from some types of sepsis. Sepsis types may have temporal patterns of sequential occurrences of these outcomes, leading to further complications, including mortality. Therefore, clinicians may depend on their intuition when analyzing time-sensitive information to make several clinical decisions for predicting early the likelihood of more than one type of sepsis co-occurring. Most previous modeling studies have focused on exploring a single sepsis type rather than multiple sepsis outcomes. Moreover, most of them use machine learning techniques in their clinics that may not accurately predict such temporal patterns of co-occurrences among different sepsis outcomes. The Abdelrahman lab has developed many temporal solutions that have been used effectively in critical care settings. Our primary goal is to develop a novel temporal solution that leverages our prior preliminary results, MIMIC IV dataset, and advanced machine learning techniques to better extracting patterns of the changes in multiple sepsis outcomes. The proposed solution's impact is to support the clinicians with an understanding of multiple sepsis outcomes. This project entails collaborations between informatics researchers and clinical experts to identify challenges and propose relevant solutions. It will require the student selected for the project and lab students to exchange ideas and solve problems together.

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Pathology | School of Medicine


IMMUNE AND METABOLIC CELL CROSS-TALK IN AUTOIMMUNE DIABETES

Maria Bettini, Associate Professor

Type 1 Diabetes (T1D) is an autoimmune disease that precipitates as a result of destruction of insulin producing beta cells by the rogue cells of the immune system. This leads to dysregulation of glucose metabolism leading to negative effects on multiple systems and disease associated complications. There is no cure for T1D. Our laboratory is investigating the interactions, both direct and indirect, between T cells and beta cells. T cells can target beta cells for destruction, but there also exists an anti-inflammatory subpopulation of T cells that can prevent or reverse autoimmunity – regulatory T cells. Regulatory T cells are currently tested in multiple clinical trials as a therapy for autoimmune diseases and transplant tolerance, but we still do not have complete understanding of their functional potential and molecular mechanisms. What is exciting, is that several molecules produced by regulatory T cells can signal directly to beta cells and potentially improve their survival under inflammatory conditions. Current work in the lab is further dissecting these signals using mouse models of T1D, flow cytometry, microscopy, and single cell genomics. We are also interested in how T cells themselves are affected by diabetes, and how they respond to changing metabolic conditions.

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neurology | School of Medicine


EFFECTS OF ALTITUDE ON BRAIN EXCITABILITY AND MIGRAINE

KC Brennan, Professor

Altitude affects the brain as well as the lungs. It is well known that high altitudes can cause severe headaches and ultimately brain swelling. It is less known that moderate altitudes, like that of Salt Lake City (SLC), can also have effects on the brain. This is important because approximately 1 billion people live at moderate altitudes. Migraine headaches are more common at moderate altitudes, and we have recently shown that migraine aura, a wave of sensory changes that precedes the headache, is significantly more frequent in people who live in SLC compared to lower elevations. This is an important clue because we know that migraine aura is caused by a spreading depolarization (SD), a wave of activity that moves across the brain like a ripple in a pond. While the pain of migraine is difficult to model in the lab, SD is readily measured. We thus have a biomarker that we can use to examine the mechanisms by which altitude affects migraine susceptibility. We have two potentially related hypotheses: 1. Hypoxia, reduced oxygen concentration, is known to trigger SD. Though there are only moderate changes in oxygen levels in SLC and other moderate elevations, they are physiologically significant, and may be sufficient to trigger SD. 2. Red blood cell mass increases significantly, even at moderate elevations. Though this helps deliver oxygen, it also makes the blood thicker and more likely to clot. Even transient clotting can trigger SD. Using optical techniques, we are able to directly visualize blood oxygenation, blood flow, and clotting, in real time in awake animals. We will use these techniques, along with an altitude chamber, to test our hypotheses in wild type mice, and in mutants carrying migraine genes.

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Internal Medicine | School of Medicine


NEURAL MECHANISMS INVOLVED IN HYPOGLYCEMIA SENSING

Owen Chan, Associate Professor

Hypoglycemia (low blood sugar) is the most serious acute complication in insulin-treated diabetes and it remains the limiting factor in maintaining proper glycemic control. The brain, and especially the ventromedial hypothalamus (VMH), plays a crucial role in sensing hypoglycemia and initiating the physiological hormone responses to correct it. However, both recurring exposure to hypoglycemia and longstanding diabetes can impair the mechanisms that normally correct the fall in blood glucose levels. Our laboratory utilizes a combination of neuroscience (microdialysis, microinjection, optogenetics), metabolic (glucose clamps), genetic (targeted knockdown or overexpression), molecular biology (qRT-PCR, westerns, immunohistochemistry) and cell culture techniques to identify the neural mechanisms that are involved in the detection of hypoglycemia and understand how these central sensing mechanisms are impaired by recurring exposure to hypoglycemia and in diabetes.

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Neurology | School of Medicine


EFFECTS OF CHROMATICITY ON MIGRAINEOUS LIGHT SENSITIVITY
Melissa Cortez, Associate Professor (Clinical)

Migraine is associated with an increased sensitivity to the sensory environment – both during, and outside of, the migraine attack. Second only to the head pain, photophobia is the most debilitating symptom reported by people with migraine. Melanopsin containing intrinsically photosensitive retinal ganglion cells (ipRGCs) are thought to play a role in migraine-associated light sensitivity, and may influence chromatic (color-specific) differences in light sensitivity. A better understanding of the effects of chromaticity in migraine-associated photophobia could have widespread benefits, including improving understanding of neural mechanisms and leading to opportunities for individualized therapies (personalized medicine). The current project will examine chromatic specificity of light sensitivity in migraine subjects. In previous work, we have found that severity of photophobia in migraine scales with disease severity, and is associated with shifts in pupillary light responses. These alterations are thought to result from centrally mediated autonomic adaptations to chronic light sensitivity. Emerging data suggests that pupillary responses to light and light sensitivity in migraineurs may be linked by differences ipRGC function. We want to follow-up this prior work by examining the chromatic-specificity of light sensitivity, and their associated pupillary responses in photophobic migraine subjects. Thus, this project will examine differences in light sensitivity in migraineurs exposed to various wavelengths of light.

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Radiology & Imaging Sciences | School of Medicine


IMPROVED METHODS FOR MEASURING CARDIAC PERFUSION AND FIBROSIS WITH MRI
Ed DiBella, Professor

The DiBella lab seeks to invent and refine new and better methods for the acquisition, reconstruction, and post-processing of MRI, with particular emphasis on cardiac and stroke applications. Our lab seeks to translate these improvements to clinical studies, and to use the methods to better understand physiology in health and disease. One set of current projects involves development of improved methods for measuring myocardial perfusion and fibrosis with MRI. Methods for higher spatial resolution, greater coverage, and elucidating differences across the cardiac cycle are being developed. We have pulse programmed new simultaneous multi-slice (SMS) and 3D acquisitions on the MRI scanner. Advanced reconstruction methods including constrained reconstruction and deep learning methods are also being developed for cardiac applications. Another project is to develop and evaluate methods for imaging the brain microstructure with diffusion MRI. SPUR students could work on either or both projects.

The stipend for this SPUR project is funded by an American Heart Association grant awarded to Dr. Stavros Drakos, MD, PhD. The stipend for this project is $4,000 instead of $5,000 due to grant funding limitations.

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InTernal medicine | school of medicine


MOLECULAR ACTIVATION OF QUIESCENT CARDIAC FIBROBLAST TO MYOFIBROBLAST IN HEART FAILURE INDUCED BY MYOCARDIAL INJURY

Stavros Drakos, Professor

Ischemic heart disease and heart failure HF is the leading cause of death and disability worldwide. Activated myofibroblast induced by injury or heart diseases adversely affects the cardiac function by depositing excess extracellular matrix and remodel the structure of myocardium resulting in increased stiffness and reduced compliance of cardiac muscle. Currently there are no effective interventions that specifically attenuate or reverse pathological cardiac fibrosis. To identify and quantify the cellular populations that correlated with quiescent and activated cardiac fibroblasts, we performed single cell RNA sequencing of non-myocytes from human non-failing hearts (donor hearts that were not allocated for transplant for non-cardiac related reasons) and failing hearts (HF). RNA expression profiles showed 2 distinct clusters characteristic of fibroblasts and myofibroblasts respectively in HF whereas non-failing heart donor reveal only one cluster of quiescent fibroblasts. The goal of this project is to investigate the molecular activation of quiescent cardiac fibroblast to myofibroblast based on the differential expression profile observed in human normal fibroblast, HF fibroblast, and myofibroblast. We will use ischemic heart model in mice to analyze expression of candidate proteins that correlated with the activation of myofibroblast after myocardial injury. The RNA inhibitor and overexpression strategies will be utilized to explore the mechanism of candidate genes in myofibroblast activation of primary cultured cardiac fibroblast.

The stipend for this SPUR project is funded by an American Heart Association grant awarded to Dr. Stavros Drakos, MD, PhD. The stipend for this project is $4,000 instead of $5,000 due to grant funding limitations.

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Biomedical informatics | school of medicine


EXPLORING THE EXPOSOME

Ramkiran Gouripeddi, Assistant Professor

About 50 – 70% of health and well-being is determined by the environment and the lifestyle of an individual lives in and their behaviors within these environments. The sum total of all the environmental exposures an individual encounters in their lifetime is called the exposome. The exposome includes molecular constituents involved in direct biological pathway alterations as well as mutagenic and epigenetic mechanisms of environmental influences on the phenome. Exposures to different chemicals have been shown to play a role in different conditions including asthma, obesity, as well as other respiratory, cardiovascular, endocrine, and metabolic conditions and cancers. Similarly, excessive use of digital devices have been linked to various mental conditions. Understanding the effects of these chemical exposures and digital device use requires representing these molecules in research studies that involve generating and utilizing exposomes. The Center of Excellence for Exposure Health Informatics (CEEHI) is developing systematic informatics methods for generating and utilizing such exposomes for performing translational research.

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Orthopaedics | School of Medicine


EFFECTS AND BEHAVIORS OF VAPING IN THE UNITED STATES

Man Hung, Professor

E-cigarettes are becoming very popular in this decade because they satisfy the psychopharmacologic desire of smoking with the smokeless delivery of nicotine. Even though e-cigarettes were introduced to the market with intentions of being an alternative to the conventional cigarette smoking, the amount of nicotine delivered to the lungs is still significant enough to cause an addiction. Some former cigarette smokers who use e-cigarettes as an alternative quit smoking, continue using nicotine-containing e-fluids. With the age of e-cigarette consumers lowering to adolescents, nicotine addiction has increased. E-cigarette’s tech-friendly device appearance is also appealing to the public that not only adults but approximately 4 million middle and high school students have embraced the vaping culture, demonstrating that this is becoming a growing concern for policy makers as e-cigarettes are becoming a gateway to cigarette smoking, especially amongst young adults. This research will use publicly available data from the Population Assessment of Tobacco and Health (PATH) Study for examining patterns and usages of e-cigarettes, in addition to investigating the effects and behaviors of vaping in the population. PATH is a population-based registry that stores national and longitudinal tobacco and e-cigarette use data in the United States.

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Biomedical Informatics | School of Medicine


REIMAGINE EHR: ENHANCING PATIENT CARE AND THE PROVIDER EXPERIENCE THROUGH STANDARDS-BASED, INTEROPERABLE EXTENSIONS TO THE ELECTRONIC HEALTH RECORD (EHR)

Kensaku Kawamoto, Associate Professor

The University of Utah’s ReImagine EHR initiative is a multi-stakeholder effort to re-imagine how patient care and the provider experience can be optimized in the EHR, including through the development, evaluation, and dissemination of innovative, interoperable extensions of native functionality provided in the electronic health record (EHR). Through ReImagine EHR, we are developing various clinical applications and decision support capabilities that are seamlessly integrated with the rest of the EHR. We are leveraging emerging health IT standards such as FHIR, SMART, and CDS Hooks with the goal of enabling these apps and services to be shared across healthcare organizations and EHR platforms. We are developing apps and services spanning the continuum of care, including prevention, chronic disease management, acute care, and transitions of care. Several of these initiatives are being pursued with the support of research grants, such as a project funded by the National Cancer Institute for identifying and managing individuals with elevated risks of breast and colorectal cancer using standards-based, interoperable, and ultimately widely scalable approaches. Another project, funded by the Agency for Healthcare Research and Quality, focuses on lung cancer screening, which could save more lives than breast cancer screening. The director of the initiative, Dr. Ken Kawamoto, MD, PhD, MHS, has been recognized for this work as a Top 25 Innovator in health care by Modern Healthcare.

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Orthopaedics | School of Medicine


QUANTITATIVE MODELING TO EVALUATE ANKLE OSTEOARTHRITIS MORPHOLOGY

Amy Lenz, Research Instructor, OUR Certified Mentor

Clinical evaluation of end-stage ankle osteoarthritis (OA) is primarily derived from 2D conventional x-rays. To improve on current medical imaging and interpretation new emerging weightbearing CT technology, a computational study is proposed to characterize ankle joint complex disease by quantifying 3D anatomical variation through statistical shape modeling of patients with ankle OA. The proposed research is relevant to public health because patients with end-stage ankle osteoarthritis are in general 10 to 15 years younger than patients suffering of knee or hip OA, making the likelihood of patients outliving current surgical treatment options a challenging clinical problem. Our lab's contribution here is expected to be a 3D computational study to characterize ankle joint complex osteoarthritis by quantifying anatomical shape variation through Statistical Shape Modeling of the tibiotalar and subtalar joints. This new and substantially different approach to computationally evaluate ankle morphometrics is expected to allow us to overcome the current limitations of clinical radiographic evaluation of ankle joint complex osteoarthritis, thereby opening new horizons for more quantifiable methods to aid in treatment planning for patients with end-stage ankle OA.

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Internal Medicine | School of Medicine


Peripheral Limitations to Maximal Oxygen Uptake in Patients with Heart Failure and Preserved Ejection Fraction
Russell Richardson, Professor

Heart failure with preserved ejection fraction (HFpEF) accounts for greater than 50% of all heart failure cases, and the prevalence relative to heart failure with reduced ejection fraction (HFrEF) continues to rise at a rate of 1% per year, with a 5-year survival rate as low as 50%. The pathophysiological differences between HFpEF and HFrEF, coupled with unsuccessful therapeutic strategies, highlight the need for improved understanding of HFpEF. The pathophysiological differences between HFpEF and heart failure with reduced ejection fraction (HFrEF), coupled with unsuccessful therapeutic strategies, highlight the need for improved understanding of HFpEF.

The defining symptom of HFpEF is marked exercise intolerance that greatly limits physical activity and quality of life. In patients with HFpEF, maximal oxygen uptake (VO2max), a primary determinant of prognosis and quality of life, has best quantified the severity of exercise intolerance. The peripheral limitations to VO2max will be determined in patients with HFpEF and controls by measuring leg maximal O2 delivery, O2 consumption, and mitochondrial oxidative capacity (Aim 1). Next, the identification of an O2-supply or O2-demand limitation will be validated by measuring the hyperoxia-induced changes in leg maximal O2 delivery and O2 consumption in patients with HFpEF and controls (Aim 2). Finally, the effect of knee-extensor training on the peripheral limitations to VO2max will be assessed by measuring the training-induced changes in leg maximal O2 delivery, O2 consumption, and mitochondrial oxidative capacity in patients with HFpEF and controls (Aim 3).

The stipend for this SPUR project is funded by an American Heart Association grant awarded to Dr. Stavros Drakos, MD, PhD. The stipend for this project is $4,000 instead of $5,000 due to grant funding limitations.

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Surgery | School of Medicine


POROUS FLUORAPATITE SCAFFOLDING WITH ADIPOSE DERIVED STEM CELLS BONE GRAFT

Jill Shea, Research Assistant Professor

Bone loss due to trauma or disease is an increasingly serious health problem within the military and civilian populations. Bone grafts are utilized in these situations to aid bone repair and regeneration. Material and performance are considered as two main problems in the development of customizable bone scaffolding. An ideal bone substitute material should have osteogenic properties and the capability to fill and integrate large bone defects with a variety of shapes and sizes. The goal of this project is to develop a scaffold that can be used to repair bone defects or injuries. The device will consist of a 3-D bone scaffold and adipose derived stem cells. The overall aims are:
1. design device
2. evaluate stem cell differentiation in vitro, and
3. evaluate in vivo efficacy in a model system.
This multi-pronged approach is hypothesized to increase bone growth following an injury and improve patient outcomes.

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Pediatrics | School of Medicine


Induced pluripotent stem cell derived cardiomyocyte models of human cardiovascular disorders
Martin Tristani-Firouzi, Professor

Advances in induced pluripotent stem cell (iPSC) technology allow for reprogramming of adult somatic cells into stem cells from which patient-specific (and thus disease-specific) cardiomyocytes (CM) can be derived. The impact of this technology has far-reaching implications, ranging from drug discovery, pre-clinical drug screening, mechanistic understanding of disease processes, and advances in personalized medicine. Specifically human iPSC-CMs offer a unique model system to study phenotypic variation in Long QT Syndrome (LQTS), by allowing for direct comparisons of gene expression in human cardiac cells derived from family members who share the same mutation, but manifest severe versus mild symptoms. However, the potential of iPSC technology to answer this and other crucial research questions is limited by several technological barriers. For example, human iPSC-CMs in culture behave more like embryonic than mature myocytes and thus may not recapitulate key features of childhood or adult-onset disease. The overall goal of this proposal is to overcome the maturational hurdles in order to design a valid iPSC-CM model system for the study human arrhythmia disorders. This proposal utilizes cutting-edge technological approaches that will advance the field of cardiovascular medicine in a very practical manner.

The stipend for this SPUR project is funded by an American Heart Association grant awarded to Dr. Stavros Drakos, MD, PhD. The stipend for this project is $4,000 instead of $5,000 due to grant funding limitations.

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Neurobiology & Anatomy | School of Medicine


ESTABLISHING THE EFFECT OF EXPERIENCE DEPENDENT PLASTICITY ON DOPAMINERGIC SIGNALING IN THE OLFACTORY BULB

Matt Wachowiak, Professor

Dopamine is a powerful neurotransmitter capable of modulating information processing throughout the brain. There is a high density of local dopaminergic interneurons and receptors in the olfactory bulb. Pharmacological manipulation of dopamine release in vivo alters the ability for mice to discriminate odorants. Likewise, decreases in dopaminergic tone and a loss of smell are associated with numerous diseases, such as Parkinson's and Alzheimer's disease. To understand dopamine's role in shaping neural circuit activity, this project will investigate how dopamine release and subsequent circuit activity changes as a function of experience.

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