Ahmed Abdel-Latif, MD  Our lab focuses on the molecular mechanisms of heart failure and the role of the immune system. We use animal models and clinical studies for our experiments. Members of the immune system such as neutrophils and macrophages play a critical role in cardiac inflammation and recovery. Specifically, macrophages are critical for tissue healing after injury in virtually every organ in the body. Alternatively, macrophages can contribute to cardiac damage after heart attack if they remain in the pro-inflammatory state for extended period of time. Modulating the macrophage state to the anti-inflammatory state (alternative polarization) is a very promising strategy to reduce the initial cardiac damage after heart attack (preservation). Our laboratory focuses on different approaches to enhance alternative macrophage polarization ranging from cell therapy to various novel and repurposed pharmaceuticals.

Daniel Beard, PhD  The Beard and Carlson lab (cooperating with Brian Carlson) is focused on systems engineering approaches for understanding the biophysical and biochemical operation of physiological systems. Dan Beard is the Director of the Virtual Physiological Rat (VPR) project, previously supported as an NIH National Center for Systems Biology, working to analyze, interpret, simulate, and ultimately predict physiological function in health and disease. The scope of topics in the lab cover integrated experimental and computational projects spanning the scales of subcellular to whole organism function and include (1) Cardiac energy metabolism. (2) Cardiovascular system dynamics. (3) Regulation of coronary blood flow. (4) Stem cell-derived cardiomyocytes.

Matt Brody, PhD   My lab focuses on intracellular signal transduction in cardiomyocytes in the context of cardiomyopathy and heart failure.  We are specifically interested in how post-translational lipid modifications modulate the localization and function of signaling molecules including receptors and GTPases.  We utilize genetic mouse models and cultured cardiac myocytes and a combination of biochemical and molecular biology techniques to interrogate molecular regulation of cardiac signaling and pathophysiology by enzymes that attach lipids to signaling proteins.  

Brian Carlson, PhD  The Carlson lab is a joint lab operating in conjunction with Dan Beard which focuses more closely on cardiovascular system dynamics and stem cell-derived cardiomyocyte electrophysiology. We utilize clinical cardiovascular hemodynamic data to elucidate patient-specific phenotypes in heart failure. Our ultimate goal is differential treatment within larger diagnoses of heart failure such as heart failure with preserved ejection fraction. On the stem cell electrophysiology front we are trying to understand how these derived cells can be used to understand the response of a native human cardiomyocyte to different pharmaceuticals.  

Adam Helms, MD  Our lab studies inherited cardiomyopathies primarily using cardiomyocytes derived from induced pluripotent stem cells with specific mutations introduced by genome engineering (CRISPR-Cas9). We have optimized bioengineered platforms to study sarcomere structure, single-cell contractile dynamics, and calcium handling in stem cell-derived cardiomyocytes. We also use genomics-based approaches to identify novel disease pathways. Our long-term goal is to identify new potential targets for medical treatment in these conditions. 

Megan Killian, MD   Musculoskeletal comorbities are on the rise with increased prevalence of cardiovascular disease and metabolic syndrome. Our research group studies the developmental and physiological mechanisms that maintain healthy tendon, muscle, and bone. Our recent work focuses on metabolic dysfunction (e.g., obesity) and cell energy homeostasis on tendon and enthesis growth and healing following injury. We use in vitro and in vivo models to explore new areas in musculoskeletal medicine.

Daniel Michele, PhD  My laboratory is interested in the molecular mechanisms of genetic cardiomyopathies in humans, particularly those associated with muscular dystrophy.  We are using genetic approaches of viral gene transfer and gene targeting in the mouse, along with functional studies in isolated cardiac myocytes and in vivo cardiovascular physiology to understand how single gene mutations lead to cardiovascular disease. 

André Monteiro da Rocha, PhD, DVM  My laboratory research focuses on modeling genetic and acquired diseases, cardiac aging and age related issues using human induced pluripotent stem cell derived cardiomyocytes to understand how age impacts physiological reserves and cardiomyocytes function. 

Anthony Rosenzweig, MD   We are interested in how exercise protects the heart and recently found that exercise induces birth of new heart muscle cells in adult (Nature Comm 2019) and aged (Circulation 2022) animals.  To understand how this happens and which cells contribute, we are performing single-cell RNA sequencing of exercised and sedentary hearts.  Students could participate in the lab experiments and/or bioinformatics integral to this project.  2.  We found that Activin signaling is important in several types of heart failure and that inhibition of this pathway can rescue heart function in multiple animal models (Science Translational Medicine 2019).  Recent data suggests an important role for inflammatory / immune cells in this effects.  A series of in vitro and in vivo experiments seek to identify the precise cells involved and molecular pathways responsible.

Rosanne Rouf, MD   My lab is focused on identifying pathogenic mechanisms in the nonmyocyte compartment that contribute to cardiomyopathy and heart failure. We are focused more specifically on how matrix proteins influence how cells in the nonmyocyte compartment behave. We believe changes in the matrix which occur in response to injury, directly reprogram endothelial, fibroblast and immune cell function. We have identified sex-specific differences in how certain nonmyocytes respond to pathogenic stimuli and are working to better understand what biological mechanisms drive these differences. A summer fellow would have a very focused project looking at sex-specific differences in cardiac fibroblast pathobiology that would involve a combination of in vitro and in vivo experiments in a murine model of cardiac fibrosis. 

Mark W. Russell, MD  My laboratory is studying mechanisms of cardiac myofibril assembly, alignment and structural support, topics central to the pathophysiology of, and development of new therapies for, heart failure, myopathy and muscular dystrophy. The laboratory has demonstrated that obscurin signals the cell to initiate the myogenic program in response to extracellular signals. As the cell begins to differentiate, obscurin scaffolds the assembly of new myofibrils and for the structural integrity of existing myofibrils. Other projects in the lab include the development of novel zebrafish models of cardiomyopathy and the evaluation of flow-mediated growth signals in the fetal heart.

Nicole Seiberlich, PhD  The Seiberlich lab works to develop new ways of acquiring MRI data and reconstructing images in order to make more rapid images of the beating heart.  This project will involve developing codes to collect and process cardiac Magnetic Resonance Imaging data.  Prior experience with coding in C, C++, or Matlab would be helpful to the success of this project.

Yatrik Shah Ph.D  Dysregulation of systemic iron homeostasis affects over a billion people worldwide. In patients with iron overload or are major cause of many serious complications including cardiomyopathyies. Although, these are distinct diseases they demonstrate dysfunction in intestinal iron absorption. Our recent publications using genetic mouse models and cell lines have shown that the transcription factor hypoxia-inducible factor (HIF)2 is critical regulator of iron absorption. Disruption of HIF2 signaling in the intestine results in low systemic iron and hematological defects, whereas a chronic increase in HIF2 signaling led to iron overload.  Recently, in animal models of iron overload, such as hereditary hemochromatosis and -thalassemia, we demonstrate that HIF2 signaling is activated. This is a critical find since alternatives to current treatments of iron overload are a high priority. Building on our recent data, we propose to identify mechanisms by which iron absorption is increased and assess the utility of HIF2 as a therapeutic target in iron-related disorders.

Alan Smrcka, PhD  My research program is interested in the physiological and pathological processes driven by G protein coupled receptor signaling. A major area of research in the laboratory is understanding the physiological and pathological roles of signaling processed that drive and protect against cardiac hypertrophy. We use cell and animal models in our laboratory to conduct these studies.

Adam Stein, MD  Dr. Stein's lab studies the importance of epigenetic mechanisms in maintaining gene expression profiles in cardiac myocytes. We have developed and characterized a murine model with altered histone methylation marks. We are currently using this mouse model to study the importance of these epigenetic marks in regulating the cardiac phenotype in disease states.

Andrea Thompson, MD, PhD  Loss of function variants in MYBPC3 are the most common cause of HCM. Still, missense variants remain poorly understood with the majority MYBPC3 missense variants classified as variants of unknown significance. Summer students will learn and execute cellular-based assays to evaluate the effect of MYBPC3 missense variants of uncertain significance on protein stability. 

Matthias Truttmann, PhD   Research in the Truttmann lab focuses on the post-translational regulation of chaperones and proteostasis. Acute and chronic stresses constantly challenge proteostasis in cardiomyocytes. Unlike most cells, however, cardiomyocytes are long-lived, hence requiring a well-regulated network of chaperones to maintain cellular proteostasis and prevent protein unfolding/misfolding. We are using a combination of in vitro and in vivo approaches to 1) identify key regulators, signaling pathways, and mechanistic principles of cardiomyocyte proteostasis regulation. Summer students will be paired with a senior lab member to contribute to an ongoing research project focusing on protein turnover in cardiomyocytes.  

Alison Vander Roest, PhD  My lab studies the mechanobiology of adult and pediatric onset hypertrophic cardiomyopathy using gene edited human induced pluripotent stem cell derived cardiomyocytes. We compare the effects of different disease-causing mutations in the motor protein (myosin) responsible for contraction in micropatterned cells with the results of computational modeling simulations of net force generation based on myosin kinetics. Our studies also relate the organization and composition of myofibrils and sarcomeres to cell specific force generation. Understanding the variability of phenotypes between different disease-causing mutations could improve the precision of developing therapeutics. 

Margaret Westfall, PhD  Research in my laboratory is focused on understanding modulation of contractile function by the protein kinase C (PKC) signaling cascade under physiological conditions, and chronic pathophysiological conditions, including ischemia and heart failure.  Using approaches such as adenoviral-mediated gene transfer of constructs into adult cardiac myocytes and into intact myocardium, our work is now focused on understanding the role played by an important target protein for PKC known as troponin I (TnI) and the influence of TnI phosphorylation on cardiac contractile performance. Troponin I is a molecular switch protein located within the sarcomeric thin filament of myocytes, and a phosphorylation target for several signaling pathways. In the future, we plan to develop vector delivery of TnI and PKC signaling constructs to failing hearts as a means of restoring cardiac performance.