Jared Churko, PhD, UA AHA SURF Program Director, Associate Professor, Department of Cellular and Molecular Medicine and Director of the UA iPSC Core. He is an expert in iPSC technologies and in using various bioinformatics (structural bioinformatics, small molecule screens, single-cell RNA-seq, HiC, ChIP-seq) approaches to understand the mechanisms leading to cardiovascular disease. Using identified biomarkers, his lab is focused on developing targeted- and patient-specific therapeutics. He has trained an extensive list of high school (6), undergraduate (15), graduate (6), medical students (2), and post-doctoral trainees (2) including several underrepresented minority students and students from diverse backgrounds. He has participated in many summer research mentoring programs including the Native Americans Research Experience for Undergraduate, Steps2Stem, Undergraduate Biology Research, Biology Research Abroad: Vistas Open, UA KEYS Research Internship and the Minority Health Disparities Summer Research Programs. Two summer students have been included as authors on peer-reviewed publications. Undergraduates will have a chance to work on several projects including:
Project 1: Cardiovascular drug screening using high-throughput contraction and calcium handling analysis on iPSC-CMs.
Project 2: Cell type specific disease mechanisms leading to arrhythmogenic cardiomyopathy
Project 3: Single-cell transcriptomic analysis of congenital heart disease mouse models.
Sakthivel Sadayappan, Ph.D., MBA, FAHA, Professor and Head of the Department of Cellular and Molecular Medicine and Associate Director, Sarver Heart Center. The long-term goal of Dr. Sadayappan’s lab is to elucidate the causes of muscle-specific diseases at the molecular level and identify targets conducive to the development of new therapies and cures. Discrete current projects include identifying cardiac-specific early biomarkers of heart failure and restoring sarcomere structure and function. These research projects have been funded by the NIH NHLBI, NIAMS, AHA, and industry for several years. His research also includes training and teaching medical students, graduate students, and post-doctoral fellows. His teaching philosophy is centered on developing the skills and personal qualities that are needed for trainees to be successful. His managerial philosophy recognizes the strengths of each individual and incorporates his/her/their strengths. Dr. Sadayappan has a long history of placing his students and fellows into academically oriented biomedical careers (see sponsor tables). Like all of the other sponsors, Dr. Sadayappan has participated in the summer undergraduate research programs and has directed several underrepresented minority students. Undergraduates will have the chance to work on several defined projects in the Sadayappan laboratory.
Project 1: Examine fast MyBP-C (fMyBP-C) on cardiac function and contractility during heart failure
Project 2: Examine slow MyBP-C (sMyBP-C) in skeletal muscle physiology
Project 3: Dissect the molecular and translational aspects of hypertrophic cardiomyopathy in patients of South Asian descent.
Henk Granzier, PhD, Professor, Department of Cellular and Molecular Medicine and Director of Molecular and Cardiovascular Research Program (MCRP). Dr. Granzier’s laboratory investigates titin and its role in normal and abnormal heart function using bioengineering, physiology, and mechanical approaches. Focus areas of research include 1) intact cardiac myocyte mechanics and study of the changes in diastolic and systolic mechanics and calcium handling in response to altering titin expression; 2) role of titin in hypertrophy signaling in cardiac muscle; and 3) the role of titin in heart failure with preserved ejection fraction (HF). He is a leading cardiovascular research scientist who directs a highly productive lab and has published nearly 300 manuscripts. He has won major research awards, including those from the AHA and has mentored numerous trainees in his lab. His research has been continuously funded by NIH for the past 30 years and he is internationally recognized in the field diastolic function. Dr. Granzier has trained 60 pre-and-post doctoral scientists the majority of whom are independent investigators in Academia and Industry.
Project 1: To determine the effect of Rbm20 antisense oligonucleotides (ASO) on titin expression and calcium handling proteins, diastolic stiffness of intact myocytes and myocardial tissue.
Project 2: To define the effect of titin’s extensible segments (N2B and PEVK elements) on longitudinal hypertrophy by using mouse models in which these elements have been targeted.
Brett Colson, PhD, Associate Professor, Department of Cellular and Molecular Medicine. Dr. Colson is a basic research scientist who focuses on myofilament proteins that regulate contraction (e.g., actin, myosin, MyBP-C). He uses biophysical approaches, such as time-resolved spectroscopy with site-directed probes to assess protein structural dynamics and mechanical measurements of isolated diseased muscle fibers. He has leveraged his technology into a high throughput novel drug-discovery platform that is accelerating the process of identification of small-molecule drug candidates for new medicine to treat cardiomyopathy and heart failure. His research projects have been supported by NIH NHLBI and NIAMS and his pre-doctoral trainees have been supported by the AHA. He tailors research projects of post-doctoral trainees and graduate and undergraduate students, including summer undergraduate research programs and underrepresented minority students, to meet their career goals in cardiovascular and biomedical research for academia and industry. Undergraduates undertaking specific research projects in the Colson lab are focused cardiac MyBP-C.
Project 1: Evaluate effects of identified MyBP-C-targeting drugs to restore normal structure and function of myofilament proteins and mouse myocardium containing cardiomyopathy mutations.
Project 2: Define the structural and functional roles of cardiac MyBP-C central domain (C3-C7) cardiomyopathy mutations, post-translational modifications, and unique linkers in the regulation of contraction and their impact on cardiac MyBP-C N-terminal domains (C0-C2).
Samantha Harris, PhD, Professor, Department of Physiology. Dr. Harris’ research group aims to understand how contractile proteins, especially myosin binding protein-C, cooperate to modulate force production by muscles and how defects in these proteins can lead to hypertrophic cardiomyopathy in heart and to skeletal muscle diseases. Her research group employs genetic, molecular, biochemical and biophysical approaches to decipher these interactions at levels from single molecules to whole organisms.
Project 1: To determine the structural and functional significance of myosin binding protein-c in cardiac muscle and how mutations in myosin binding protein-c contribute to inherited and acquired cardiac diseases.
Project 2: To determine the structural and functional significance of myosin binding protein-c in fast and slow twitch skeletal muscle fibers and how mutations in these proteins contribute to debilitating diseases such as distal limb contractures (e.g., club foot) and a newly discovered class of inherited muscle tremors originating from mutations in contractile proteins.
Shanna Hamilton, PhD, Assistant Professor, Department of Cellular and Molecular Medicine, Member of the Cardiovascular Research Program and Sarver Heart Center, AHA BCVS Early Career Committee Member. The overarching goal of Dr. Hamilton’s laboratory is to decipher molecular mechanisms of calcium regulation in the healthy and diseased heart, with the end goal of uncovering novel therapeutic strategies to treat arrhythmias and heart disease. Current projects include investigating how signaling pathways, such as endoplasmic reticulum stress, contribute to calcium-dependent arrhythmias. Projects are funded by the NIH NHLBI, foundation grants and a generous start up package. The Hamilton laboratory provides an excellent training environment to study cardiovascular disease from the molecule through to the organism level. Trainees will be exposed to molecular biology, high-resolution confocal microscopy and live cell imaging, electrophysiology, whole heart optical mapping and in vivo gene editing. Since opening her laboratory in July 2023, Dr. Hamilton has recruited students at the MS, Ph.D, and MD/Ph.D level, and has participated in several University of Arizona undergraduate research programs including the Ronald E. McNair Achievement Program. Dr. Hamilton is highly committed to teaching and mentoring the future generation of independent research scientists in an inclusive environment, and will be supported by senior faculty in the program. Undergraduates will have the opportunity to work on two defined projects.
Project 1: Defining new molecular mechanisms of catecholaminergic polymorphic ventricular tachycardia (CPVT)
Project 2: Examining the impact of endoplasmic reticulum stress in calmodulinopathy.