Y. Eugene Chen, MD, PhD  Although important advances have been made in recent years in our understanding nuclear receptors in the regulation of metabolism, development, differentiation, inflammation, growth and programmed cell death, relatively little is known about the effects of these nuclear receptors and their ligands on the regulation of vascular smooth muscle cells. The objective of our projects is to begin to define the role of these transcription factors as endogenous regulators of pro-atherogenic and anti-atherogenic genetic programs that couple perturbations in lipid metabolism to vascular cell function. In particular, we focus our initial effort on two classes of receptors: (1) the liver X receptor (LXR), and (2) the peroxisome proliferator-activated receptors (PPARs).

Salim Hayek, MD   Our research focuses on using biomarkers to predict a patient’s risk for disease, potential outcome from a treatment or intervention, or to help guide a patient’s treatment plan.  We are currently investigating the effects of the biomarker suPAR (soluble urokinase plasminogen activator receptor) on disease pathogenesis; in human studies, suPAR is highly predictive of cardiovascular outcomes and there is some evidence that the presence of suPAR itself may cause damage. We’re examining this possibility using mouse models of atherosclerosis, myocardial infarction, or hypertension, by comparing genetic overexpression or deletion of the gene. 

Cindy H. Hsu, MD, PhD   Our research focuses on the discovery and translation of novel neuroprotective therapies for cardiac arrest patients by developing clinically relevant large animal models. We validate the efficacy of candidate therapies with multimodal approaches that include blood-based brain injury biomarkers, electrophysiology, digital neuropathology, pharmacokinetics studies, high throughput sequencing analysis, and neurocognitive tests.  

Tom Kerppola, Ph.D.  Our laboratory uses novel experimental approaches to investigate molecular mechanisms of cardiac diseases.  We have developed methods that enable visualization of protein interactions and modifications in cardiomyocytes and analysis of chromatin binding complexes in freshly isolated heart tissues.  We have identified transcription factor complexes that control cardiomyocyte hypertrophy in response to the balance of growth promoting and growth modulating stimuli.

Daniel A. Lawrence, PhD  A significant area of interest focuses on the vascular biology of the CNS and its relationship to CNS disease processes. A second area study is the development of fibrotic disease. In particular, how upregulation of the protein PAI-1 promotes the pathogenesis of thrombotic and fibrotic diseases, and on the development of novel therapeutic interventions for the treatment of thrombotic and fibrotic diseases. Our studies use combinations of biochemical, molecular, and genetic approaches.

Venkatesh Murthy, MD   Our research focus is in the use of multi-omics and advanced cardiovascular imaging to improve our understanding of cardiac and metabolic diseases. We use data from patient cohorts, clinical trials as well as large epidemiologic studies (MESA, CARDIA, Framingham) using computational methods to integrate metabolomics, proteomics and genomics with integrate imaging data from CT, MRI and echocardiography. We also develop and validate quantitative imaging biomarkers using cardiac PET and CMR imaging in both patient cohorts and clinical trials.

David J. Pinsky, MD  The predominant research focus is to elucidate the mechanisms by which blood vessels modulate their phenotype following periods of interrupted blood flow.  Efforts are underway to elucidate the signal transduction mechanisms by which endogenous and inhaled CO exert their homeostatic regulatory effects on injured blood vessels. Various animal models are used in the laboratory to understand the pathophysiological consequences of ischemia-induced microvascular dysfunction. Ultimately, the goals of the laboratory are to develop new insights into endogenous mechanisms of ischemic vascular injury and protection, in order to develop new therapeutic strategies  targeted at the intersection of thrombotic, fibrinolytic, and inflammatory axes.

Marschall Runge, MD, PhD & Nageswara Madamanchi, PhD   The Runge laboratory is interested in understanding the role of oxidative stress in the development of atherosclerosis and hypertension which are key risk factors for myocardial infarction and stroke. The most important source of reactive oxygen species in vascular cells are the multiple forms of enzymes nicotinamide adenine dinucleotide phosphate oxidase (NADPH oxidase). Genetically engineered mouse models are being used to demonstrate the key NADPH oxidases that regulate oxidative stress in the cardiovascular system in order to identify targets for the therapeutic prevention of cardiovascular disease.

Thomas Sanderson, PhD  Research in the Sanderson lab is focused on understanding brain damage caused by ischemic insults during cardiac arrest, ischemic stroke, and neonatal hypoxia/ischemia. Two primary avenues of investigation are (1) the role mitochondrial dysfunction in death of neurons during post-ischemic reperfusion and (2) the development and clinical translation of neuroprotective therapies that modulates the activity of mitochondria to reduce ischemia-reperfusion injury.

Michael Wang, MD, PhD  My laboratory focuses on the causes and consequences of ischemic stroke, a leading cause of cardiovascular death and disability.  A major effort in the lab is to understand the molecular changes that occur in blood vessels of the brain in CADASIL, an inherited disorder that results from mutations in NOTCH3.  Additional lines of research include studies of effects of stroke on circadian rhythms, sleep, and autonomic function and approaches to enhance recovery after neurological injury.  We integrate investigations of human tissues, genetically modified animals, and cellular models and use physiological, molecular & cellular techniques.

Peter Henke, MD, FACS, FAHA   Led by Dr. Peter K. Henke, the Leland Ira Doan Professor of Surgery, the Henke Lab investigates how blood clots in venous thrombosis (VT) resolve over time and how they damage the vein wall as they do. Dr. Henke's work as a vascular surgeon enables our laboratory to ask, and answer, important questions that impact patients' lives and outcomes following VT. Our lab has been funded since 2003 by the National Institutes of Health, the American Venous Forum and other organizations.

Michael Holinstat, PhD  Platelet activation is the final step in maintaining hemostasis following vascular injury. Likewise, unregulated platelet activation leads to occlusive thrombus formation, MI, and stroke. My lab focuses on understanding the complex signaling mechanisms that regulate hemostasis and thrombosis. The work in my lab focuses on four primary areas of platelet research spanning from a basic science and drug discovery program to clinical and translational projects including a clinical trial focused on platelet function in type 2 diabetes mellitus, clinical studies on racial disparity in platelet activation and thrombotic risk, identification of novel bioactive lipids in the platelet, and development of first-in-human inhibitors for the prevention of thrombosis and stroke. The models  used in the lab to study these areas of platelet biology include several healthy and patient human cohorts as well as animal proof of principle studies using intravital microscopy, aggregometry, flow cytometry, and other techniques.

Jason Knight, MD  Diabetes mellitus is associated with preclinical macrovascular dysfunction, which predicts the development of atherosclerosis and negative long-term outcomes for diabetic patients. NETosis is a unique form of neutrophil-related cell death whereby massive webs of chromatin and antimicrobial proteins are released into the extracellular space to neutralize infections. While overexuberant NETosis has been associated with accelerated cardiovascular disease in various contexts, its role in diabetes is mostly unstudied. Here, we plan to leverage wire myography, pharmacological approaches, and RNA-seq analysis to determine the role of NETosis in the macrovascular dysfunction of diabetic mice.

James Morrissey, PhD  We are investigating how the blood clotting cascade is regulated, with applications to thrombotic diseases, bleeding disorders, and inflammation. Our lab has recently discovered that polyphosphate (an inorganic polymer of phosphate present in many infectious microorganism and secreted by activated human platelets) is a novel modulator of the blood clotting cascade and may represent the long-sought (patho)physiologic activator of the contact pathway of blood coagulation. Our current research efforts focus primarily on: (1) Understanding, with atomic-scale resolution, how blood clotting proteins interact with membrane surfaces and how these membrane binding events contribute so profoundly to catalysis; and (2) Understanding the mechanisms by which polyphosphate modulates the clotting system in hemostasis, thrombosis and inflammation.

Daniel Myers, DVM, MPH   Venous thrombosis and pulmonary embolism are significant national healthcare concerns. Thrombus and vessel wall damage promotes the up-regulation of adhesion molecules, tissue factor (TF), and inflammatory mediators in vivo. Utilizing animal models, The laboratory have defined the contribution that adhesion molecules, TF, and cytokines play during thrombosis. Recent research suggests that hypoxic and chemical injury to vascular endothelium contributes to the pathogenesis of several cardiovascular diseases. Our research evaluates the effects venous endothelium dysfunction post oxidative injury. Our goal is to define the role of oxidative injury in the pathogenesis of venous thrombosis.

Andrea Obi, MD   Our laboratory, led by Andrea T. Obi, MD(link is external), studies a type of abnormal blood clotting, venous thrombosis, or VT. Our work has led us to look more closely at the role of the immune system and epigenetics in clot formation and breakdown. In fact, we are one of very few laboratories in the world working in this promising area of discovery. Our goal is to take our findings and translate them into new, safer and more effective approaches to treating VT.

Jordan Shavit, MD, PhD  Our laboratory studies the genetics of human blood clotting disorders using zebrafish and mouse models.  Pathologic blood clotting (thrombosis) is responsible for significant patient morbidity and mortality, including deep vein thrombosis, pulmonary embolism, myocardial infarction, and stroke.  We have developed models of thrombotic disorders using genome editing nucleases, such as CRISPR.  These models are being used for large-scale zebrafish mutagenesis screens to identify genetic and chemical modifiers of thrombosis. This will be followed by investigation of these modifiers in mouse models and human populations.

Justus Anumonwo, PhD  A number of cardiac rhythm disturbances have been associated with mutant ion channel proteins, accessory proteins to the ion channels, or the improper interactions between the two proteins. Research in our laboratory focuses on understanding the molecular interactions of cardiac ion channel proteins under normal and patho-physiological conditions. We use a combination of electrophysiological, biochemical and molecular biological techniques to carry out these investigations.

Omer Berenfeld, PhD   Our research focuses on mechanisms of complex wave propagation and fibrillation in the heart using a combination of experimental, clinical, and numerical approaches, with the aim of better understanding acute and chronic atrial fibrillation as well as ventricular fibrillation. We investigate the basic effects of the ionic and structural properties of the heart on the normal and abnormal propagation of its action potential, and particularly the effects on the unique phenomenon of rotor activity. Our research and developments use analysis in the time, phase and frequency domains together with novel opto-electric approaches for mechanistic correlations between the fibrillatory activation patterns and the cardiac substrate. Emphasis is given to technological developments enabling the translation of knowledge derived from animal and computational models into the clinical setting of patients with atrial fibrillation. 

Jimo Borjigin, PhD    We have developed a new method of displaying and analyzing long streams of EKG signals, called the electrocardiomatrix (ECM). This method preserves all features of cardiac electrical signals decipherable from raw EKG data in a compact manner and permits a single-glance view of time-dependent changes of heart rate and the occurrence of cardiac arrhythmias. The ECM method appears to offer superior sensitivity and specificity for cardiac arrhythmia detection compared with manual detection (Li et al., 2015b) as well as automated arrhythmia detection (manuscripts in preparation) and is predicted to improve diagnosis of cardiac diseases.  Currently, we are collaborating with a number of physicians to conduct a small scale clinical trials to test the sensitivity and specificity of ECM approach for cardiac arrhythmia detection at the University of Michigan Hospital.  

Lori Isom, PhD    Variants in ion channel genes can lead to neurological or cardiovascular diseases called channelopathies. Our work focuses on human variants in genes encoding voltage-gated sodium channel α and β subunits that lead to a devastating pediatric epileptic encephalopathy called Dravet syndrome, a disease with a high risk of Sudden Unexpected Death in Epilepsy (SUDEP). We have proposed that SUDEP arises from simultaneous arrhythmias of brain and heart due to the expression of mutant sodium channel genes in both organs.  Our ultimate goals are to discover novel targets for epilepsy therapeutics and to identify biomarkers for SUDEP risk.

David K. Jones, PhD   Ion channel dysfunction causes the cardiac disorder long QT syndrome. Long QT syndrome patients have an elevated risk for sudden cardiac death. Our lab uses patient-derived and gene edited human stem cell-derived cell lines as models of the human heart and brain. Using techniques in electrophysiology, immunocytochemistry, and molecular biology, we seek to understand the impact of ion channel dysfunction on human physiology and its contribution to sudden death.

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 processes 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 the 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. 

Gorav Ailawadi MD, MBA   Aortic Aneurysms are the 15th leading cause of death in the United States and corrective aneurysm repair through either open or endovascular surgery remains the only treatment therapy for this deadly disease. Often, aneurysms remain clinically undiagnosed and under-represented as many deaths perceived to be from cardiac arrest are actually from aneurysm rupture. Aneurysms are anatomically divided by their location in reference to the diaphragm with thoracic aneurysms (TAAs) located above while abdominal aneurysms (AAAs) are located below the diaphragm. Recent evidence suggests that these diseases have different disease pathologies that could be based on the embryological origin of the aortic layer and thereby could have different medical treatment therapies. Sadly, the mechanisms of aortic aneurysm formation and advanced aneurysm disease leading to rupture remain largely unknown. It is unknown why some patients have small aneurysms that rupture while other patients rupture at considerably larger aortic diameters. Dr. Ailawadi and his team seek to understand the mechanisms that regulate aortic aneurysm rupture in abdominal and descending thoracic aortic aneurysms. He and his team have spent a number of years developing novel animal models for the study of aneurysm rupture and utilize these models to develop medical therapies to halt disease progression or prevent rupture.

Brendon Baker, PhD  My lab studies how structure and mechanics of the cellular microenvironment guide fundamental cell processes such as migration, proliferation, and extracellular matrix synthesis.  We develop synthetic biomaterials that mimic the 3D and fibrous nature of stromal or interstitial tissues which are critical to the function of vascular and cardiac tissues.  Combined with molecular tools, live imaging, microfabrication/fluidic techniques, and multi-scale mechanical characterization, these materials allow us to model, study, and control the interactions between cells and their surroundings.  Ultimately, our aim is to 1) provide insight into extracellular matrix-mediated diseases such as fibrosis and 2) use material cues to direct cell function for tissue engineering and regenerative medicine applications.  

Tae-Hwa Chun, MD, PhD    Our research is focused on extracellular matrix (ECM) remodeling in obesity, diabetes, and cardiovascular diseases. In the body, metabolically active mesenchymal cells are surrounded by a fibrous network of ECM proteins, for example, collagens, elastin, and fibronectin. Embedded within the dense network of ECM proteins, fat cells (adipocytes) and their precursor cells constantly change their shape and function in response to nutritional and hormonal cues. 

L. Michel Espinoza-Fonseca, PhD   The goal of my group is to understand the fundamental molecular motions and interactions that are responsible for regulating calcium transport in muscle cells, and to design pharmacological therapies to treat human diseases associated with dysregulation of calcium transport in the heart. My laboratory pursues two areas that relate closely to each other: 1) Fundamental biophysics of calcium pump regulation and functional adaptation, and 2) Therapeutic modulation of cardiac calcium pump activity, specifically by small molecules targeting allosteric effector sites in the transmembrane domain of the protein. We approach these multidisciplinary problems with a combination of computational methods and experimental techniques. We welcome summer students interested in computational and/or experimental work.

Mario Fabiilli, PhD   The Fabiilli lab develops ultrasound-based therapies with a focus on biomaterials for drug delivery and tissue regeneration, including strategies for blood vessel and bone growth. The Fabiilli lab leverages ultrasound-induced effects to non-invasively and spatiotemporally modulate both biochemical and biophysical signals to direct cell behaviors.

Jonathan Haft, MD and Alvaro Rojas Pena, MD ECMO Lab:  The laboratory runs a wide variety of surgical and bioengineering research projects, including the development of artificial lungs, artificial kidneys, biomaterials, and techniques for expanding the pool of donated organs.  Artificial lungs are a particular focus, with work on several different generations of implantable artificial lungs, new gas exchange membranes, and new applications for these devices, such as an artificial placenta, ECMO assisted organ donation, ECMO assisted cardio-pulmonary resuscitation and ex-situ solid organ (heart, lungs, kidneys) and composite tissue allografts preservation and conditioning to transplantable status.

Todd Herron, PhD  Our research relies on the use of human induced pluripotent stem cells to generate patient-specific hearts in vitro for disease modeling, drug testing, and therapy development. We utilize 2D monolayers of the purified patient-specific heart muscle in high throughput electrophysiology screens to enable robust data acquisition and rigorous scientific analysis. Additionally, we utilize 3D-engineered heart tissues to generate patient-specific heart muscle with physiologically relevant features. Students in my laboratory will learn to work with patient-specific stem cells to generate heart tissues in vitro for analysis using a combination of molecular biology, fluorescent microscopy, optical mapping, and metabolic phenotyping approaches.  

David Humes, MD  Development of biomimetic devices to treat acute and chronic organ disorders. Our lab does preclinical large animal studies, molecular, biochemical and cell assays, and evaluates biomarkers of patients being treated with our innovative devices.

Young Park, PhD   Our research group is creating point-of-care (POC) technologies that enable precise, quick, and sensitive detection of important biomarkers associated with the state of illnesses.  

Anna Schwendeman, PhD  Dr. Schwendeman’s long-term research goal is to design highly potent and safe synthetic high-density lipoprotein (HDL) nanomedicines for treatment of atherosclerosis. Dr. Schwendeman spent 12 years in pharmaceutical industry at Cerenis Therapeutics, Pfizer, and Esperion Therapeutics. She was involved in discovery and translation of several HDL therapies to Phase II clinical trials. Her efforts led to development of a kilo-scale recombinant process for Apolipoprotein A-I (ApoA-I - main HDL protein) for the largest-to-date Phase II sHDL clinical trial (>500 patients). Her current research interests focus on understanding the mechanisms of how phospholipid composition of HDL affects its potency and pharmacokinetics and designing novel ApoA-I mimic peptides. Her laboratory has several ongoing translational projects focused on assessing sHDL’s utility for treatment of atherosclerosis, sepsis, Alzheimer's disease and lupus as well as for use these “nature-made” nanoparticles for targeted delivery of drugs to the arteries.  

David Sherman, PhD  Drug Discovery and Development Efforts Employing Unique Chemical Diversity Resources against Cardiovascular Targets:  The University of Michigan Center for Chemical Genomics, and the recently initiated Center for the Development of New Medicines provides state-of-the-art resources for drug discovery and development programs. These include high throughput screening, medicinal chemistry and pharmacokinetic resources. 

Laurie, Svoboda, PhD  My research program is focused on understanding the sexually dimorphic effects of developmental chemical exposures on cardiac differentiation and long-term cardiovascular health. My team and I utilize mouse and induced pluripotent stem cell models to investigate how lead (Pb), perfluoroalkyl substances (PFAS), arsenic, and phthalate plasticizers disrupt the sex-specific epigenetic and metabolic processes that underlie normal cardiovascular development and differentiation.  We can carve out a project that aligns with these overall goals for a SURF student.

Zhong Wang, PhD  Our long-term goal is to develop heart therapies to effectively prolong and improve the life of heart patients. Cardiovascular disease (CVD) is the leading cause of death in the world and is often accompanied with defective blood vessel network in the heart. One research interest is to define the epigenetic mechanism mediated by ATP-dependent chromatin remodeling in cardiac progenitor specification and differentiation. A second interest is to define essential cross-talk between energy metabolism and epigenetics in heart repair and regeneration. A third interest is to explore novel strategies to generate cardiac progenitor cells and engineered cardiac tissues suitable for heart regeneration. A fourth interest is to identify epigenetic factors and small molecules/drugs in stimulating heart regeneration.

Bo Yang, MD, PhD  Our research is focused on the unknown mechanism of thoracic aortic aneurysm (TAA), especially in those with unknown genetic mutations. Under the efforts by our research team that combining different expertise of molecular/cellular biology, bioengineering, and vascular surgery, we first create patient specific induced pleuripotent stem cells (iPSCs) from variety kinds of TAA patients, such as bicuspid aortic valve (BAV), Loyes-Dietz Syndrome, and Marfan syndrome. We then perform in vitro disease modeling to recapture aortapathy of these disease using both 2D cell culture and 3D pulsatile physiologic-mimic bioreactors.  With lab-made tissue engineering blood vessels (TEBVs) that derived from patients’ vascular smooth muscle cells, we further implant patient-specific TEBVs into immunodeficient animals to model human TAA in vivo with the aims of knowing physiopathology of human TAA and developing the strategy for drug therapy. Taking the advantage of new CRISPR/Cas9-based gene editing, we have successfully corrected the specific TAA patient’s mutation in patient-derived iPSCs and provide a new platform to study the mechanism of human TAA in the levels of molecular and cell biology, organogenesis, as well as body vascular system. 

Richard Auchus, MD, PhD  We study the biochemistry of enzymes responsible for the production of steroid hormones that regulate blood pressure, including aldosterone and cortisol. We have developed mass spectrometry methods to profile these steroids and precursors in vivo and in vitro for basic and clinical studies. We are particularly interested in using these methods to improve the diagnosis and management of primary aldosteronism, which account for ~8% of hypertension.

J. Brian Byrd, MD, MS  The Byrd Lab is interested in discovering new ways to diagnose cardiovascular disease and guide its treatment. Thus, key activities in the laboratory include processing human biofluids and performing a variety of types of assays to evaluate signals from those biofluids. The skills learned in the lab will inform projects students undertake in the future, whether those projects are in a cell, a mouse, or a patient. Students entering the laboratory will work hard, will learn about human physiology and pathophysiology, and will work directly on translational research at the lab bench.

C. Alberto Figueroa, PhD,  Our laboratory focuses on methods and applications for computational modeling of hemodynamics using image-based approaches. From a methods perspective, we are developing machine learning formulations for improved geometry segmentation, formulations to study coagulation in image-based models, and methods for non-linear simulations of vessel wall-blood flow interactions. On the experimental side, we develop novel MRI techniques for tissue perfusion quantification and photoacoustic methods for in-vivo thrombus imaging. Our group also has projects that investigate the interplay between vascular stiffness and hypertension, both systemic and pulmonary.

Santhi Ganesh, MD  My lab is focused on understanding the genetic and functional basis of vascular diseases that are characterized by adverse vascular remodeling. The diseases we study include atherosclerosis, hypertension and rare diseases such as fibromuscular dysplasia and spontaneous coronary artery dissection. The methods we use include human genetic screens (genome-wide association, sequencing) and vascular biology basic techniques (in vitro cellular assays, animal models). Students engaged in research in this laboratory can be expected to gain understanding of human genetics and vascular biology, with a specific focus on how these areas of research can be translated to the clinical setting.

William E. Rainey, PhD  Dr. William (Bill) Rainey is the Jerome Conn Professor in the Departments of Molecular and Integrative Physiology and Internal Medicine. For over 30 years, his group has researched the cellular, biochemical, and molecular mechanisms that regulate adrenal steroid hormone biosynthesis and related adrenal diseases such as Primary Aldosteronism (PA). PA is the main cause of endocrine hypertension and the most common adrenal disease.  About 1 in 30 adults have PA and the impact of inappropriate aldosterone production in the face of hypertension includes a significant increase in the potential for stroke, renal disease and cardiovascular disease. My laboratory takes a bench to bedside approach to 1) defining the molecular mechanisms that cause PA, 2) improving diagnostics to facilitate PA screening, and 3) developing the cell and mouse models that improve our understanding of PA. The Rainey lab group includes post-graduate clinician and basic scientists as well as graduate and undergraduate students. Summer Undergraduate Research Fellows (SURFs) would join ongoing research projects that are applying genomic and steroid metabolomic approaches directed at improving the understanding of PA or other adrenal diseases.

Dr. Juilee Rege, PhD   Dr. Rege is a Research Investigator in the department of Molecular & Integrative Physiology within the Rainey Laboratory.  Her group's research goal is to determine the genetic causes underlying adrenal Cushing syndrome (CS), a common endocrine cause of cardiovascular morbidity. Adrenal CS is caused by autonomous cortisol production in one or both adrenal glands and affects 0.2–2 % of adults. Chronic exposure to endogenous glucocorticoid excess is associated with a cluster of complications including visceral obesity, dyslipidemia, hypertension, diabetes mellitus, osteoporosis, and recurrent infections. Our research adopts both basic and translational approaches utilizing human adrenal tissue, serum and cell lines in order to: (i) define the genetic landscape of adrenal CS, particularly with regard to adrenal somatic mutations that cause cortisol excess; (ii) define serum steroid biomarkers using LC-MS/MS to facilitate adrenal CS subtyping; and (iii) develop the cell models that improve our understanding of adrenal CS.

Kanakadurga Singer, MA  There are several projects in the Singer lab all focused on gaining an understanding of the long-term impacts of diet-induced obesity on the immune system.  Immune system activation is strongly linked with risk for metabolic and non-metabolic diseases. Hence, gaining a greater understanding of how diet-induced obesity affects the immune system can provide new biomarkers for identifying at risk individuals and novel treatment approaches.

Adina Turcu, MD   Our research includes basic and translational projects that aim to facilitate personalized care for patients with hypertension. We focus on the development of novel biomarkers for simplifying the diagnosis and subtyping of primary aldosteronism and other forms of hypertension.  We use state-of-the art mass spectrometry to quantify steroids from small volume blood samples. We are also working on defining mineralocorticoid receptor (MR) modulators by using an in vitro model, that allows the detection of both direct and indirect (via cortisol, by inhibiting its local inactivation) MR agonists.