Sarver Heart Center selects 2023-2024 Investigator Award recipients

For the 2023-2024 grant cycle, the University of Arizona Sarver Heart Center awarded 7 Investigator Awards.

Director’s Message

The Sarver Heart Center is proud to continue its tradition of supporting innovative research through the Investigator Awards. We extend our heartfelt gratitude to our donors whose unwavering commitment fuels the success of this program. These awards primarily empower early career investigators and trainees to pursue groundbreaking pilot projects. The significance of this investment is exemplified by the consistent transformation of preliminary data from these projects into substantial external grant awards.

“As we embark on the new fiscal year, the Investigator Awards exemplify the very essence of Sarver Heart Center's mission. They foster, nurture, and promote cardiovascular research that holds the potential to shape the future of patient care. We are honored to embrace this legacy of dedication and discovery," stated Elizabeth Juneman, MD, director of the Sarver Heart Center. “Together, we march forward into a future where innovative research propels us closer to the heart of better health."


Novel Research Project Awards in the area of Cardiovascular Disease and Medicine


Targeting Peroxiredoxin-4 as a Novel Therapeutic Approach to Prevent Calcium-Dependent Arrhythmia

Scientist: Shanna Hamilton, PhD, assistant professor of cellular and molecular medicine
Support provided by: Sharon K. West, Ella Waltz & Thomas Berresford, Dr. Robert S. and Sydney Heller, and Mark and Emma Schiffman

Calcium-dependent arrhythmias and irregular heart rhythms triggered by calcium ion influx are critical issues in cardiovascular diseases. While we understand that disturbances in calcium and redox balance contribute to this problem, we lack a clear picture of the underlying molecular mechanisms. This knowledge gap hampers our ability to develop effective treatments for arrhythmias.

Shanna Hamilton, PhD, assistant professor of cellular and molecular medicine, is employing innovative methods to bridge this gap. To create an effective treatment for calcium-dependent arrhythmias, she is testing a model of catecholaminergic polymorphic ventricular tachycardia (CPVT), a highly malignant arrhythmia syndrome. Using genetic probes and gene editing techniques, Hamilton will quantitatively measure calcium and reactive oxygen species in heart cells. These tools allow her to uncover the cellular processes leading to arrhythmias and test the therapeutic potential of a protein called Peroxiredoxin-4 (PRDX4) to mitigate the condition.

The goal of this study is to develop a novel therapeutic approach for calcium-dependent arrhythmias in cardiovascular diseases. By characterizing the CPVT model, targeting PRDX4 to reduce calcium mishandling in heart cells, and assessing PRDX4's impact on arrhythmias at both the cellular and whole heart levels, it aims to demonstrate the effectiveness of PRDX4-based interventions. This research has significant clinical implications, supporting future proposals for the National Institutes of Health and advancing our understanding of endoplasmic stress in heart health.

The Investigator Award will significantly bolster Dr. Hamilton's research by funding essential components of her study. It will support the purchase of crucial fluorescent dye (Fluo 3-AM), the production of viral strains for genetic interventions, and echocardiography services. This financial support ensures the smooth execution of experiments, data collection, and analysis, ultimately advancing the understanding of cardiac arrhythmias and calcium signaling.


Can Inspiratory Resistance Training improve Cerebrovascular and Cognitive Functions in Patients with Above-Normal Blood Pressure and Endothelial Dysfunction?

Scientist: Dallin Tavoian, PhD, postdoctoral research associate
Support provided by: The Alex Frazer and Frank H. Frazier Cardiovascular Research Award, Archie Clifford and Clara Mabel Rentfrow, and Anthony and Mary Zoia

Cerebrovascular disease (CBVD) impacts blood vessel function in the brain and increases stroke and dementia risk. Preventative medication has limitations. Non-pharmacological interventions, like exercise, have shown promise but are often impractical for most adults. Dallin Tavoian, PhD, postdoctoral research associate, proposes Inspiratory Resistance Training (IRT), a 5-minute exercise requiring only a hand-held device against a high resistance (75% of maximal strength). IRT has been shown to enhance the ability of the endothelial lining of blood vessels to regulate blood flow and reduce blood pressure, making it a promising tool for improving cerebrovascular health.

This pilot study aims to assess if six weeks of IRT can enhance cerebrovascular and cognitive function in adults with high blood pressure and compromised vascular health. To expand this research, Dr. Tavoian plans to collect data for a subsequent R01 grant application. This work has the potential to provide valuable insights into novel, time-efficient therapies for cerebrovascular diseases and cognitive decline, addressing an urgent need for effective interventions beyond medications.

The Investigator Award will significantly support Dr. Tavoian's research by facilitating the acquisition of essential equipment, such as the transcranial ultrasound probe, Airofit Pro 2.0 training devices, and other necessary supplies. These resources are vital for conducting high-quality cerebrovascular assessments and cognitive function measurements in patients with above-normal blood pressure and endothelial dysfunction. The funding will enhance the accuracy and efficiency of the study, ensuring reliable results and supporting the investigation of potential interventions for cerebrovascular and cognitive health.


Understanding Diabetic Lipid Signature in Plaque Vulnerability

Scientist: Wei Zhou, MD, FACS, chief of the Division of Vascular and Endovascular Surgery
Support provided by: Ralph and Shirley Morgan Cardiovascular Research Award, John T. and Janet K. Billington, and an anonymous donor. 

Atherosclerosis-related cardiovascular disease poses a significant global health threat, especially in patients with diabetes. Despite knowing that diabetes contributes to an increased likelihood of plaque rupture, the specific impact of intraplaque lipid composition remains poorly understood. This knowledge gap leads to suboptimal treatment strategies for atherosclerotic patients. The key challenge is to identify reliable biomarkers predicting vulnerable plaques in diabetic populations.

Wei Zhou, MD, FACS, chief of the Division of Vascular and Endovascular Surgery, uses research methods that employ cutting-edge analytical lipidomic screening techniques, particularly tandem mass spectrometry. This method allows for a detailed analysis of lipid species in carotid plaques and plasma samples, revealing distinct profiles in diabetic versus nondiabetic patients. Collaborating with lipidomic cores at Washington University and the University of Arizona, the team delves into seventy-nine lipid species, providing a comprehensive understanding of intraplaque lipid signatures. This innovative approach includes exploring enzymes involved in lipid metabolic pathways, paving the way for novel therapeutic targets.

The primary goal of Dr. Zhou's research is to characterize intraplaque lipid signatures in diabetic and nondiabetic patients. By comparing these signatures with plasma lipid profiles, the study aims to unravel the specific lipid components actively contributing to plaque vulnerability in diabetes-related cardiovascular disease. Ultimately, Dr. Zhou seeks to identify a lipidomic signature that can serve as a reliable biomarker, paving the way for novel lipid-targeted therapies to prevent and manage vulnerable plaques in diabetic patients, thereby reducing atherosclerosis-related mortality and morbidities.

The Investigator Award will advance Dr. Zhou's research by funding crucial elements: personnel for sample maintenance and validation, consumables for varied experiments, user fees for Lipidomic and Proteomics Cores, and a statistic consultant to enhance lipidomic and proteomic analyses. The inclusion of a statistic consultant ensures the accuracy and reliability of lipidomic and proteomic analyses, ultimately enhancing the overall quality and depth of the research.


Single Cell Transcriptomics for Deep Phenotyping of Methamphetamine associated PAH

Scientist: Cole Uhland, MD, T32 cardiovascular medicine fellow
Support provided by: the Dr. J. Allen Ginn, Jr. endowed fund  

Pulmonary arterial hypertension (PAH) is characterized by elevated blood pressure in the pulmonary arteries, increasing workload on the right side of the heart and potentially leading to heart failure. PAH has been definitively linked to methamphetamine use, but knowledge gaps surrounding methamphetamine-associated PAH (meth-PAH) exist, hindering targeted therapeutic approaches. Previous studies hinted at clinical disparities between meth-PAH and PAH resulting from unknown (idiopathic) causes (iPAH), necessitating an in-depth exploration of their transcriptomic differences.

To address this gap, Cole Uhland, MD, a T32 cardiovascular medicine fellow, proposes using single-cell RNA sequencing (scRNA-seq) as a cutting-edge tool. ScRNA-seq allows for the examination of individual cell gene expression profiles, revealing transcriptional variations within cell populations. By focusing on pulmonary arterial endothelial cells obtained during right heart catheterization, the study aims to compare the transcriptomic signatures of meth-PAH and iPAH. This advanced technique provides a more nuanced understanding of the molecular differences, offering insights into pathogenesis and potential therapeutic pathways.

Upon completion, this research will provide a detailed evaluation of transcriptomic differences between meth-PAH and iPAH. The study aims to identify genes associated with pathogenesis and therapeutic pathways, shedding light on mechanistic disparities between these subtypes. Furthermore, Dr. Uhland plans to explore if transcriptomic signatures are consistent across different endothelial cell types and to assess differences in the transcriptomics of right ventricular (RV) function in meth-PAH versus iPAH. The goal is to enhance the accuracy of meth-PAH phenotyping at a transcriptomic level, potentially paving the way for tailored diagnostic and prognostic studies and informing future therapeutic strategies.

The Investigator Award will significantly advance Dr. Cole Uhland's research by covering the essential costs of scRNA-seq, including libraries and sequencing. With a focus on four patients (eight samples), this funding ensures in-depth transcriptomic analysis, enhancing our understanding of methamphetamine-associated PAH at a molecular level.


Titin kinase, master switch for eccentric hypertrophy of the heart

Scientist: Robbert Jan Van der Pijl, PhD, postdoctoral research associate
Support provided by: William J. “Billy” Gieszl Endowment and the J.G. Murray Memorial Endowment

Dilated Cardiomyopathy (DCM), the enlargement of a heart’s left ventricle leading to impaired pumping, is a leading cause of heart failure, affecting individuals of all ages and backgrounds. DCM involves over 250 genes, manifesting as lengthening of cardiac muscle cells (cardiomyocytes), leading to impaired cell contraction. The underlying hypertrophy mechanism, especially related to increased cardiomyocyte length (longitudinal hypertrophy), remains unclear, hindering targeted therapies for DCM.

Focusing on titin, a giant elastic protein spanning the sarcomeres, Robbert Jan Van der Pijl, PhD, postdoctoral research associate, aims to investigate its kinase domain's activity using innovative genetic models and manipulations of adenosine triphosphate (ATP) binding affinity. This approach allows him to explore the intricate mechanics of longitudinal hypertrophy and its connection to DCM development. 

To conduct this research, Dr. Van der Pijl employs two models: tnK36A, with reduced ATP-binding affinity, and the proposed TtnM34V, mirroring a patient mutation. By inducing volume overload and studying cardiomyocyte responses, he aims to establish the impact of ATP binding on titin kinase activity. Furthermore, using recombinant proteins and skinned papillary muscle, he plans to unravel the kinetics of ATP binding to titin kinase. Through ATP-binding studies in these two models, Dr. Van der Pijl aims to clarify titin kinase's role in DCM development, particularly in cardiomyocyte length regulation. This may unveil potential therapeutic targets. The study contributes vital pilot data for future grant applications and enhances understanding of DCM progression.

The Investigator Award will significantly support Dr. Van der Pijl's research by covering crucial expenses, including the generation of models, laboratory supplies for molecular studies, service fees for essential core facilities, and mass spectrometry analysis to deepen our understanding of titin kinase in Dilated Cardiomyopathy.


Undergraduate/Medical Student Awards


Sleep and Cardiovascular Health (IN-BeD Study)

Scientist: Michael Amadei, undergraduate student majoring in biochemistry and physiology & medical sciences, with Michael Grandner, PhD, MTR, CBSM, FAASM, assistant professor of neuroscience and physiological sciences
Support provided by: Margarito Chavez Undergraduate / Medical School Student Awards 

The "IN-BeD Study" aims to investigate the profound connection between sleep and cardiovascular health in a way that is easy to understand. Adequate sleep, at least 7 hours per night, supports heart health by promoting lower blood pressure and better heart rate variability, an indicator of physical fitness. Michael Amadei, an undergraduate researcher, seeks to unravel how sleep duration, timing and quality affect resting heart rate and heart rate variability.
By studying 20 young adults aged 18-25, Amadei will analyze the impact of cardiovascular activity on their sleep patterns, cognitive performance, and mood. Participants will wear Fitbit devices, maintain sleep diaries, and record their food intake. They will spend time in a sleep lab where they will experience partial sleep restriction conditions.

Amadei’s project will examine the role of heart rate changes (captured using wearable Fitbit devices) in the relationship between sleep quality and dietary choices. Heart rate typically drops during sleep and sharply increases during nocturnal awakenings. Amadei hypothesizes that the increased heart rate during wakefulness when the body is expected to be asleep can lead to increased stress-related unhealthy eating behaviors. Amadei plans to present his findings at the SLEEP 2024 conference, contributing to the field of sleep research and enhancing our understanding of how to achieve better heart health through improved sleep and lifestyle choices. In April 2023, Amadei was accepted into the College of Medicine – Tucson’s Honors Early Assurance Program (HEAP) as part of the Class of 2028.

Sleep and Cardiovascular Health (IN-BeD Study)

Scientist: Sofia Garber, undergraduate student majoring in biochemistry, physiology & medical sciences, and Spanish with Michael Grandner, PhD, MTR, CBSM, FAASM, assistant professor of neuroscience and physiological sciences
Support provided by: Margarito Chavez Undergraduate / Medical School Student Awards

According to Principles and Practice of Sleep Medicine, at least a third of Americans, including shift workers, students, and those with sleep disorders, experience disrupted sleep patterns. While poor sleep and misaligned circadian rhythm are associated with cardiovascular health issues, the mechanisms underlying this connection, particularly impulsive nocturnal eating, are not well understood.

The "IN-BeD Study" seeks to unravel how cognitive and emotional factors interact during nighttime wakefulness, potentially leading to unhealthy eating choices and ultimately impacting cardiovascular health. Garber’s study will enroll 20 young adults aged 18-25, tracking their sleep and eating behaviors in real-life settings using Fitbit devices and the MealLogger app. Subsequently, they undergo a two-weekend sleep laboratory intervention, during which they receive standardized meals and snacks. Participants complete neurocognitive assessments using an iPad to evaluate mood and cognition throughout the day. This holistic protocol enables a thorough examination of how nocturnal wakefulness influences mood-driven eating behaviors.

Garber aims to determine whether nighttime wakefulness impairs cognitive functions and contributes to unhealthier food preferences. Furthermore, she seeks to explore the extent to which these factors play a role in the development of obesity, a well-known risk factor for cardiovascular diseases. Garber plans to conduct her honors thesis using this data and present it at the SLEEP 2024 Conference. In the future, Garber plans to attend medical school.