SPUR 2020 Projects: Medicine

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

biomedical informatics | School of Medicine


AN UNSUPERVISED LEARNING ANALYSIS TO IDENTIFY SUBGROUPS IN WOMEN WITH PREGNANCY COMPLICATIONS
Samir E. Abdelrahman, Assistant Professor

 

Around 10% of pregnant women in the US suffer from placental insufficiency due to several common pregnancy complications including preeclampsia, placental abruption, and intrauterine fetal growth restriction (IUFGR), stillbirth, and Neonatal Intensive Care Unit (NICU). Despites there is extensive research in modeling the causes placental insufficiency; but identifying the relationships among predictors of pregnant women are still open research area. Most of current research studies have limited to analyze few categories of predictors. In this study, we will utilize broad categories of predictors: namely, demographics (age, race, ethnicity, sex of fetus); social determinants of health (income, education, social support); parameters of ultrasounds; medications and vaccinations; food intake; vital signs; and placental analyses.  In this study, we will focus on studying a multi-site real dataset that has cohorts of women from different states with one or more mentioned complications causing placental insufficiency. We will analyze the predictors of these complications during pregnant women visits with respect to these complications in the delivery visits. We will use unsupervised machine learning techniques to reduce the number of dataset predictors and identify patient subgroups that present potential frequent relationships among predictors with respect to women complications. This project entails collaborations between informatics researchers and clinical experts to identify challenges and propose relevant solutions. We will require the student selected for the project and lab students to exchange ideas and solve problems together.

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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.

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


AN UNSUPERVISED LEARNING ANALYSIS TO IDENTIFY SUBGROUPS IN WOMEN WITH PREGNANCY COMPLICATIONS
Karen Eilbeck,  Professor

 

As sequencing technologies have advanced; sequencing data has shown the extent of polymorphism in the human population. Understanding which of these DNA changes impact an individual’s clinical phenotype (cause disease), and which are silent is necessary for the interpretation of genetic tests.  ClinVar is an international, submission-driven archive of variant-condition-interpretations hosted by the National Center for Biotechnology Information (NCBI). ClinVar is increasingly becoming the central repository of interpreted genomic variants; as of July 2018, 997 submitters had contributed 427,882 unique variants and 11099 conditions to ClinVar. Sharing variants and associated supporting evidence in the ClinVar database enables the transparent review of data by users and supports clinical variant interpretation. Submissions to ClinVar represent the first time that clinical labs and other submitters have shared and compared their variant interpretations, and this reveals both conformity and discrepancy in variant interpretation. In some cases the disagreement in interpretation is clinically significant – pathogenic versus benign. This growing and evolving database relies on submitters to resolve discrepancies and update findings when knowledge changes. It also provides the starting point for expert curation of variants and genes. My group developed ClinVar Miner (https://clinvarminer.genetics.utah.edu/ ); a tool that enables deep exploration of the ClinVar dataset. The goal of ClinVar Miner is to enable management of the upstream and downstream processes related to submitting to and using the data. ClinVar Miner as a counterpoint to facilitate use of ClinVar data.

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biomedical informatics | School of Medicine


EXPLORING NOVEL ASPECTS OF 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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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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Biochemistry | School of Medicine


MACROPHAGE-TUMOR CELL CROSSTALK

Minna Roh-Johnson, Assistant Professor

Macrophages are one of the body's first responders to infection. They eat debris, attack foreign substances, and help keep the body healthy. So then it is surprising that macrophages can play a sinister role in tumors. Instead of attacking cancer cells, macrophages promote metastasis of many cancers. What kind of communication occurs between macrophages and cancer cells for this to occur? To answer these questions, we use a combination of animal models and cell culture techniques to visualize and manipulate macrophage behaviour when in contact with cancer cells. We also visualize cancer cell behaviour during specific steps of metastasis in living animals. With these approaches, we have discovered unexpected modes of cell-cell communication between cancer cells and their environment, and are now determining the molecular mechanisms of this communication.

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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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