Faculty mentors are categorized along with short descriptions below. A more detailed description of each mentor can be found by clicking the faculty name.
Atherosclerosis, Myocardial Infarction, and Stroke
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).
Daniel T. Eitzman, MD The major focus of the laboratory is to determine the impact of various genetic alterations on atherosclerosis and arterial thrombosis using in vivo mouse models. We have developed models of vascular injury in the setting of atherosclerosis that allow us to identify the impact of many genes and conditions on atherothrombosis. To address the broader role of adipose tissue inflammation in vascular disease, we have recently developed a model of visceral fat inflammation and demonstrated that visceral, but not subcutaneous fat inflammation, is sufficient to accelerate atherosclerosis – in the absence of diabetes. Results of these studies have potential therapeutic implications and may provide insight towards links between obesity and cardiovascular disease.
Daniel Goldstein, MD Dr. Goldstein’s laboratory is interested in how aging impacts chronic vascular inflammation. The laboratory team works in experimental murine models to understand how aging impacts vascular diseases such as atherosclerosis and heart transplant vasculopathy. They also work on how aging impacts acute inflammation during influenza viral lung infection. We welcome Summer students to engage in projects related to aging and inflammation.
Tom Kerppola, PhD 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 The Lawrence laboratory studies the role of proteases and their inhibitors in health and disease. A primary area of interest focuses on the vascular biology of the CNS. The principal targets of this work are members of the serine protease inhibitor (serpin) family of proteins, their target proteases, and their downstream protease substrates. A long standing interest has been understanding why the current standard of care for thrombotic stroke, thrombolysis with tissue plasminogen activator (tPA), is not effective when given more than 4.5 hours after the onset of ischemic stroke and why tPA treatment significantly increases the risk of hemorrhagic conversion. Studies involve examining the role of tPA in regulating the blood brain barrier. Another area if interest is focused on understanding the development of peripheral vascular and fibrotic disease. In particular how upregulation of the protease inhibitor plasminogen activator inhibitor 1 (PAI-1) promotes the pathogenesis of thrombotic and fibrotic diseases.
Richard M. Mortensen, MD, PhD The major goal of my laboratory has been to understand basic mechanisms in the consequences and treatment of obesity, diabetes and related cardiovascular disease. Major focus has been on the role of PPAR (peroxisome proliferators-activate receptor) transcription factors in adipose tissue formation, cell growth and cardiovascular disease (vascular and cardiac dysfunction in diabetes). This PPAR-γ transcription factor is the target of an effective class of insulin sensitizers, the thiazolidinediones that treat Type II diabetes and ameliorate cardiovascular complications.
Robert W. Neumar, MD, PhD Our laboratory studies cardiac arrest resuscitation. Active areas of investigation include goal-directed CPR, extracorporeal CPR (ECPR) using percutaneous cardiopulmonary bypass, mechanisms of neuronal injury caused by cardiac arrest, and neuroprotective stategies such as therapeutic hypothermia.
David 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 The Runge laboratory is interested 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 cardiovacular system in order to identify targets for 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.
Blood Disorders and Thrombosis
Jose Antonio Diaz, MD Dr. Diaz's research interests are in the mechanism involved in deep vein thrombosis (DVT), specifically the link between inflammation, thrombogenesis, fibrosis secondary to DVT, identification of potential therapeutic targets for DVT and animal models of DVT. Dr. Diaz's studies of interluekin 6 (IL-6) revealed that it may serve as a potential therapeutic target to ameliorate fibrosis associated to the post-thrombotic syndrome. Dr. Diaz’s research also investigates the potential benefits of statins to prevent DVT. In addition, Dr. Diaz is investigating the role of galectins on DVT. Galectins are well-known players in cancer progression and metastasis but its role on DVT is still unknown; this is an area of interest for Dr. Diaz.
Joan Greve, PhD Leveraging my decade-plus experience in biotechnology, my lab at Michigan pursues precision approaches in our preclinical studies of the cardiovascular (CV) system. We do this by developing robust and reproducible preclinical MRI techniques to define population variability in the healthy and diseased CV system of our animal models, while simultaneously quantifying the magnitude and variability in therapeutic response. This approach is requisite because successful translation of therapeutic development work in preclinical models requires: 1) understanding how the healthy and disease models replicate or differ from the human condition; and, 2) comparing data from studies performed across many years using the same methods. Physiology and pathophysiology we focus on includes thermoregulation, peripheral artery disease, and deep vein thrombosis.
Peter Henke, MD Jobst Vascular Research Laboratory: Our laboratory focuses on venous thrombosis resolution and vein wall injury. We use surgical models of deep vein thrombosis and genetically modified mice as well as immunological, genetic and physiological assays to define the pathophysiology with the goal of better agents to treat this disease. Our current focus is on the cytokine interleukin-6 and the monocyte/macrophage.
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.
Yogen Kanthi, MD We are investigating the mechanisms by which veins develop thrombosis, a particularly insidious and potentially fatal disease that has a high morbidity and mortality. The predominant focus of our lab is to understand how the venous system adapts to environmental changes (hypoxia, inflammation, high pressures) that can result in venous thrombosis. Our lab has recently discovered that critical vascular enzymes important in anticoagulation also maintain homeostasis by reducing inflammatory cytokines which exacerbate thrombosis. Our current research efforts include cell culture experiments complemented by multiple animal models to understand the modifiers of venous thrombosis, in order to develop new therapeutic agents.
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.
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.
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.
Thomas Wakefield, MD In my laboratory, we are studying the role of inflammation in venous thrombosis, its development and its resolution. We are looking specifically at the molecules P-selectin, plasminogen activator inhibitor-1, and von Willebrand fator. We use multiple in-vitro and in-vivo models.
Cardiac Electrophysiology and Arrhythmias
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- physiologial 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 wave propagation and fibrillation using a combination of experimental, clinical, and numerical approaches with the aim of better understanding of 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 correlation of activation patterns with the ionic and structural properties of the atrial 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 L. Isom, PhD Mutations in ion channels and their non-pore-forming subunits can lead to cardiovascular disease. Ion channels are part of large, multi-protein complexes, comprising the channel pore and its non-pore-forming subunits, components of the cytoskeleton, regulatory kinases and phosphatases, trafficking proteins, extracellular matrix proteins, and possibly even other ion channels. This project will investigate the biochemical and functional association of beta 1 subunits of voltage-gated Na+ channels with Na+ and K+ channels in heart, using Scn1b null mice which demonstrate elecrophysiological abnormalities including prolonged QT intervals. In addition, we will investigate human patient-derived induced pluripotent stem cell cardiac myocytes with mutations in SCN1B.
Jose Jalife, MD We investigate the molecular mechanisms and nonlinear dynamics of heart rhythm and conduction disturbances. Our studies are aimed at improving diagnosis and treatment of complex arrhythmias, including atrial fibrillation and ventricular fibrillation and preventing sudden cardiac death. Other areas of research include studies on the role of ion channel macromolecular complexes in the mechanisms of cardiac excitation and fibrillation; non-linear dynamics of excitation and propagation in isolated cardiac tissues; application of video-imaging techniques to study wave propagation and spiral wave formation in cardiac muscle; and the study of the cellular and molecular mechanisms underlying sudden death in inherited arrhythmogenic diseases. More recently we established single cell, 2D and 3D platforms of human induced pluripotent stem cell-derived cardiomyocyte (hiPSC-CMs) to investigate cardiac electrical abnormalities in diseases such as arrhythmogenic right ventricular cardiomyopathy, hypertrophic cardiomyopathy, Duchene muscular dystrophy and Hutchinson-Gilford progeria, as well as mechanisms of cancer drug cardiotoxicity
Anatoli Lopatin, PhD The lab research revolves around the understanding the molecular mechanisms of function, localization and regulation of a specific class of potassium channels called inward rectifiers, or Kir channels, in the heart, with the ultimate goal to understand their role in the normal cardiac electrical activity of the heart as well as in the genesis of life-threatening arrhythmias. The major approaches include experimentation with isolated hearts from wild type and transgenic mice expressing mutant Kir2 channels using Langendorff perfusion system, patch-clamp electrophysiology of single cardiomyocytes and cultured cells expressing cloned Kir2 channels, work with various relevant fluorescent indicators and experiments involving confocal microscopy.
Cristen Willer, PhD The summer undergraduate would be working with the CHIP biobank team to build a phenotypic database on atrial fibrillation cases. They will develop some database and computer experience, familiarity with MiChart and clinical research experience.
Cardiomyopathies and Heart Failure
Sharlene Day, MD Our laboratory is interested in molecular mechanisms of hypertrophic and dilated cardiomyopathies. We focus in particular on defects in protein degradation by the ubiquitin proteasome system, and how this system is differentially regulated in diseased hearts. We utilize human tissue samples, mouse, and in vitro model systems.
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.
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.
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.
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.
Jason Weinberg, MD Adenoviruses are also common causes of myocarditis. Research in my laboratory is focused on understanding interactions between adenoviruses and host immune responses. We use a mouse pathogen, mouse adenovirus type 1 (MAV-1), to study the pathogenesis of adenovirus myocarditis, capitalizing on our ability to study the pathogenesis of a virus in its natural host. Our research seeks to characterize contributions of host factors such as interferons and prostaglandins to the control of viral replication in the heart and virus-induced cardiac dysfunction.
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.
Cardiovascular Drug Delivery, Devices, and Tissue Engineering
Lola Eniola-Adefeso, PhD Due to their high specific interaction with their counter-receptors and their carefully regulated expression (limit to inflammation), leukocyte-endothelium adhesion molecules (LECAM) are attractive molecules for vascular targeting in human diseases in which inflammation plays a role. Our research goal is to use knowledge of the cellular inflammatory response and blood flow dynamics to design bio-functionalized particles for targeted drug delivery and imaging.
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 My laboratory studies excitation-contraction coupling mechanisms in healthy and diseased heart muscle. There is an emphasis on the heart's molecular motor myosin and its role in health and disease. One aspect of research in the lab is focused on mechanisms whereby a mutant contractile protein can predispose the heart to the development of fatal arrhythmias.
Andrew Putnam, PhD Our research interests are in cardiovascular bioengineering and regenerative medicine. We are focused on developing strategies to direct vascularization and tissue regeneration, with the goal of developing new therapies for peripheral arterial disease and ischemic cardiomyopathies. Fundamental research in our laboratory seeks to understand how the extracellular matrix (ECM), the body’s natural scaffolding material, influences both normal and pathological cardiovascular development. We then seek to leverage this fundamental knowledge to inspire the design of “instructive materials” for applications in regenerative medicine and as model systems in which to study cardiovascular disease.
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.
Ming-Sing Si , MD Vascularization of Engineered Heart Tissue Laboratory engineered heart tissue (EHT) may overcome many of the obstacles of current treatment of end stage heart failure and congenital heart disease. In order for EHT to be clinically relevant, it must possess a vasculature and perfusion. Our laboratory is focused on establishing perfused vasculature in human EHT through tissue engineering, pluripotent stem cell culture and differentiation into cardiomyocytes, bioreactor design and construction and neovasculature formation. Summer undergraduate fellows will have the opportunity to participate in any of these areas with the ideal goal of completing a concise project.
Robert U. Simpson, PhD My research is focused on elucidating the health importance and molecular mechanism of action of 1,25 Dihydroxyvitamin-D. We discovered the actions of the vitamin D hormone on cardiovascular tissues and shown that use of analogs of this hormone are clinically promising for the treatment and prevention of cardiovascular disease. The Simpson lab was the first to elucidate the role of 1,25(OH)2D3 in regulation of cardiovascular function and structure.
Paul Tang, MBBS, PhD My cardiovascular research involves determining the role of innate immunity on modulating the function of human donor hearts and failing native hearts. There is an opportunity to be involved in ex-vivo isolated human heart perfusion experiments and well as experiments in a pig model. The role of innate immunity will also be explored in a human cardiomyocyte culture system. Using advanced OMICS techniques (genomics, transciptomics, and proteomics), we correlate biological parameters with clinical outcomes for patients undergoing ventricular assist device implantation, extra-corporeal membrane oxygenation and heart transplantation. Furthermore, trainees can be involved in other clinical outcomes research with presentation of results in national and international meetings.
Zhong Wang, PhD The long-term goal of the Wang laboratory is to develop stem cell based heart therapies to effectively prolong and improve the life of heart patients. We are tackling a few roadblocks in heart regeneration in order to fulfill this goal. One roadblock is the poor understanding of the molecular mechanism of cardiac stem/progenitor cell (CPC) specification and differentiation. The second roadblock is the inefficient strategies to produce CPCs and engineered cardiac tissues suitable for heart regeneration. The third roadblock is the lack of appropriate large animal models for preclinical studies.
Bo Yang, MD, PhD Our research is focused on the mechanism of thoracic aortic aneurysm which is largely unknown, especially in those with unknown mutations. We use patient specific induced pleuripotent stem cells (iPSCs) to model the thoracic aortic aneurysm, and study the mechanism of aneurysm formation in bicuspid aortic valve (BAV), Loyes-Dietz Syndrome, and Marfan syndrome. We also use CRISPR Cas 9 technology to create and correct the mutations causing thoracic aortic aneurysm in control and patient's iPSCs. We are collaborating with Dr. Cristen Willer to identify novel gene mutations in BAV patients and study the biological mechanisms of novel gene mutations using BAV. Finally, we have been working on generating tissue engineered vascular graft with patient's iPSCs. Clinically, we have a robust team doing outcome research of aortic surgery and adult cardiac surgery.
Vascular Biology and Hypertension
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
Lou D'Alecy, DMD, PhD Project Area 1: Origins and fate of asymmetrical dimethylarginine (ADMA). This area of activity involves the "dissection" of blood into its constituents and evaluation of the ability of each component to produce and or eliminate free ADMA, one of the key endogenous inhibitors of nitric oxide synthase. Project Area 2: Hypoxia, hypoxic tolerance, and hypoxic conditioning mimics and pathways. This area will likely involve mouse and possibly rat models of hypoxia and hypoxic conditioning. A series of drug candidates will need to be evaluated for efficacy and ability to up regulate specific signaling pathway.
Jonathon Eliason, MD This laboratory is currently focused on the harmful properties of cigarette smoke and electronic cigarette vapor on vascular cell biology, with an emphasis on changes related to abdominal aortic aneurysm pathogenesis. Electronic cigarettes are currently the most common form of “smoking” in adolescents. Their effects on the cardiovascular system are largely unknown. Using cigarette smoke as a comparator, we are performing in vitro and in vivo experiments to evaluate these effects. The in vivo experiments utilize a novel environmental smoke/vape chamber for inhalational exposure of rodents. Acute and chronic changes to the aorta following exposure are then evaluated. Preliminary results suggest significant alterations in pathways related to inflammatory cell recruitment, adhesion, and activation, apoptosis, and extracellular matrix remodeling.
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.
Ronald W. Holz, MD, PhD The major interest of the laboratory concerns the mechanisms underlying Ca2+-dependent exocytosis. The processes we are studying are fundamental to the release of hormones and neurotransmitters by neurons and endocrine cells. The molecular mechanisms underlying secretion of prepackaged hormones and neurotransmitters are being studied using primary adrenal chromaffin cells in tissue culture. Biochemical, molecular genetic and optical techniques are being employed to study the effects of specific proteins on regulated secretion. We are investigating the nature of the internal milieu of secretory granules using a variety of biophysical techniques. An important aspect of our approach is the use of a powerful optical technique, total internal reflection microscopy (TIRFM), to study granule motion, biochemical events immediately adjacent to the plasma membrane during exocytosis, and the granule interior. Of particular interest is tissue plasminogen activator (tPA), which is expressed endogenously in chromaffin cells and is secreted during stress together with catecholamine. This proteolytic enzyme initiates proteolytic cascades that regulate thrombolysis in the circulation and paracrine/autocrine mechanisms in the adrenal medulla. Following secretory granule fusion with the plasma membrane the discharge of tPA is exceedingly slow (~10s). We are investigating the mechanisms for this slow post-fusion discharge.
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
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.