A diverse faculty of over 80, representing 36 different divisions and departments but thematically integrated to incorporate clinical and basic science across the spectrum of CVP disease, constitutes our mentors.

To provide foci whereby the merging of clinical and basic science is seen to address a specific clinical need, we have identified subgroups of research interest. The strength of this approach is the vertical integration of basic and clinical research programs that enrich the training experience, enabling the medical student to appreciate how clinically relevant research questions can be addressed by the joint efforts of multiple disciplines, and how these efforts can provide new insights into pathophysiological mechanisms of disease and treatment options.

Those students choosing the original research option will participate as a member of this integrated team.

Faculty Mentors for Cardiovascular-Pulmonary Science Concentration

Myocardial Ischemia, Heart/Respiratory Pump Failure and Transplantation

Dan Bernstein, M.D., Pediatric Cardiology
Cardiomyopathy, adrenergic receptors and polymorphisms, transgenic mice, transplantation

Our lab has several major focuses:

1. The role of the G protein coupled receptors in regulating cardiac function, and specifically mitochondrial structure and function.

2. Differences between right and left ventricular responses to stress and in their modes of failure, including gene expression and miR regulation.

3. Using iPSC-derived myocytes to understand heart failure and congenital heart disease.

4. We develop tools for evaluation of cardiovascular physiology in transgenic and knockout mice and in isolated cardiomyocytes.ce.

Specific projects underway in our lab include:

1. Evaluation of the role of beta1 and beta2 adrenergic receptor subtypes in regulating cardiac structure and function by studying mice with targeted gene disruption of these receptors. Evaluation of the role of crosstalk between beta receptors and other signaling pathways in regulating cardiac structure and function.

2. Role of beta receptors in regulation of mitochondrial structure and function, including processes of mitofusion, mitofission, autophagy and mitophagy.

3. Role of beta receptors in adriamycin cardiotoxicity.

4. Differences between the right and left ventricles in their responses to stresses such as increased afterload and increased preload, including gene expression and gene regulation by micro-RNAs.

5. Using patient-derived iPSC-cardiomyocytes to understand the mechanisms of cardiomyopathies common in children. Evaluation of mitochondrial function in iPSC-CMs and the ability of these cells to recapitulate mitochondrial abnormalities seen in patients with cardiomyopathy. Using iPSC-CMs to understand the mechanisms of heart failure in congenital heart disease, specifically in patients with systemic right ventricles.

6. Development of micro-engineered platforms for assessment of biomechanics of single native or iPSC-derived cardiomyocytes.

We also are interested in clinical cardiac transplantation in children, specifically:

1. Understanding the mechanisms of antibody mediated rejection.

2. Development of biomarkers for the detection and monitoring of post-transplant lymphoproliferative disorder in pediatric transplant patients.

Profile & Publications

Helen Blau, Ph.D., Microbiology & Immunology 
Stem Cell Biology 

Recent/current research projects and current associated publications:
1. mdx/telomerase - Duchenne muscular dystrophy (DMD) is the most common life-threatening muscle disorder of childhood, manifested by progressive myopathy of skeletal and cardiac muscles. A limitation in development of therapies for DMD is the lack of mouse models that recapitulate the functional and pathophysiological deficits in the human disease. Despite their lack of dystrophin, mdx mice, the most commonly used mouse model to date, do not develop the severe myofibrosis and cardiomyopathy typically seen in DMD patients. It is known that telomerase activity plays an important role in cell proliferation and senescence. As mice have telomeres four times longer than humans, we assumed that long telomeres help the skeletal and cardiac muscle cells meet the high demand for continuous regeneration in mdx muscular dystrophy. By reducing the length of telomeres in the mdx mice, we generated mice that develop a more severe dystrophic phenotype that mimics the pathophysiology of human patients. Our recent data show that this discrepancy results from the differential regenerative potential of muscle satellite cells of humans and mice, in response to muscle damage. We propose to extend our studies by using the newly generated dystrophic mouse model in order to (a) study the cardiac phenotype and understand the etiology of cardiac failure in DMD, (b) test methods for manipulating telomerase structure and delivering minidystrophin that may be a potential cure for the skeletal and cardiac disease in humans.

2. Stem cell niche –
 Sacco, A., Doyonnas, R., Kraft, P., Vitorovic, S. and Blau H.M. (2008) Self-renewal and expansion of single transplanted muscle stem cells. Nature 456:502-506. Cited in Faculty of 1000

- Gilbert, P.M., Havenstrite, K.L., Magnusson, K.E.G., Sacco, A., Leonardi, N.A., Kraft P., Nguyen, N.K., Thrun, S., Lutolf, M.P. and Blau, H.M. (2010) Substrate elasticity regulates skeletal muscle stem cell self-renewal in culture. Science, published in Science EXPRESS online July 15, 2010.

3. AID - Bhutani, N., Brady, J.J., Damian, M., Sacco, A., Corbel, S.Y. and Blau, H.M. (2010) Reprogramming towards pluripotency requires AID-dependent DNA demethylation.  Nature 463:1042-1047. [Epub ahead of print doi:10.1038/nature08752]. Cited in Faculty of 1000

4. Dedifferentiation - Pajcini, K.V., Corbel, S.C., Sage, J., Pomerantz, J.H. and Blau, H.M. (2010) Transient inactivation of Rb and ARF yields regenerative cells from postmitotic mammalian muscle.  Cell Stem Cell, accepted for publication – Aug. 6, 2010 issue [doi:10.1016/j.stem.2010.05.022].

Profile & Publications

Brian Kobilka, M.D., CV Medicine 
Adrenergic regulation of cardiovascular physiology; The structure and mechanism of activation of adrenergic receptors

Profile & Publications

Daria Mochly-Rosen, Ph.D., Chemical and Systems Biology 
Drug design, cardiac ischemia and reperfusion, heart failure, protein kinase C activators and inhibitors, drug design, mitochondrial functions, alehyde dehydrogenases, nitroglycerin

Profile & Publications

David Rosenthal M.D., Pediatric Cardiology
Pediatric heart failure and transplant

Potential Projects:
1. Evaluation of RV wall motion: A comparison of CT and MRI modalities. The evaluation of RV motion is of increasing importance given the availability of RV cardiac resynchronization. Techniques for the evaluation of RV motion are under development. It is of interest to determine whether current CT scanners offer sufficient temporal and spatial information to provide for a detailed analysis of RV motion.
2. Development of CT-based strain imaging: Measurement of regional LV and RV function is difficult and techniques are suboptimal. Echocardiography offers excellent temporal resolution but limited windows. MRI offers excellent imaging of the LV , but RV wall tagging is difficult. A new technique of speckle tracking may overcome these issues but has not been implemented in CT data. This is a pilot study to develop this technique.
3. Intra-operative RV resynchronization: RV resynchronization is conceptually and practically achievable, but the best methods for realizing this goal are not determined. This is an intra-operative evaluation of different approaches to RV resynchronization, in order to develop information about RV electro-mechanical interactions and improve the ability to achieve RV resynchronization.

Profile & Publications

Donald Schreiber, M.D., Surgery (Emergency Medicine)
Acute Myocardial Infarction, Acute Coronary Syndrome, Congestive Heart Failure

Potential research projects:
1) Ischemia Modified Albumin (IMA), A Novel marker of myocardial ischemia in acute coronary syndrome. This multicenter project will enroll emergency department patients with acute coronary syndrome. Study subjects will undergo serial blood tests for IMA to validate it sensitivity, specificity and negative predictive values as well as risk stratificiation for patients with acute coronary syndrome.
2) The impact of rapid bedside testing of cardiac markers on the ER management of patients with suspected acute myocardial infarction. This randomized open study will directly compare patients managed using rapid bedside testing with a novel analyzer for Troponin-I to the traditional central lab methods.
3) PANDA study- High dose tirofiban a glycoprotein IIB/IIIA inhibitor as adjunctive therapy for acute ST segment elevation MI

Profile & Publications

Joseph B. Shrager, M.D., Cardiothoracic Surgery
Respiratory Muscle Pump - Cellular/molecular Physiology

Dr. Joseph Shrager is Professor of Cardiothoracic Surgery and Chief of the Division of Thoracic Surgery.  He moved to Stanford from the University of Pennsylvania in mid-2008 and has spent the last year rebuilding his productive research lab, which is now ready to move aggressively ahead with ongoing and new projects. His work has focused upon elucidating, and then intervening in, the cellular and molecular mechanisms that underlie skeletal muscle function and dysfunction.  Most recently, the lab has been focused upon skeletal muscle atrophy in response to "disuse," and particularly upon disuse atrophy of the diaphragm in response to mechanical ventilation.  The lab's publication describing this "ventilator-associated diaphragm atrophy" was the lead article in the New England Journal of Medicine in March 2008.  His work has also been published in other important journals such as Nature,PNAS,  The Journal of Thoracic and Cardiovascular Surgery, and The American Journal of Respiratory and Critical Care Medicine.

Ultimately, it is hoped that a therapy can be brought to clinical trials.  Techniques used in the lab include cell culture, transgenic mice, high-throughput screening, and all the usual modern molecular and cell biologic tools. The lab is anxious to have interested students and fellows join in our work.

Current active projects in the laboratory:
(1) Detailed analyses of the molecular pathways active in ventilator- and drug-associated muscle atrophy
(2) High- throughput screening for candidate drugs that might prevent this atrophy, 
(3) Evaluation of these candidate drugs in mouse and rat models of ventilator-associated diaphragm atrophy.

Profile & Publications 
http://thoracicsurgery.stanford.edu/people/shrager_bio.html

Jim Spudich, Ph.D., Cell Biology 
Cellular mechanisms of force generation
Profile & Publications

Randall Vagelos, M.D., CV Medicine 
Myocardial ischemia and injury
Profile & Publications

Joseph Wu, MD, Ph.D., Medicine/Radiology

Our lab studies the biological mechanisms of adult stem cells, embryonic stem cells, and induced pluripotent stem cells. We use a combination of gene profiling, tissue engineering, physiological testing, and molecular imaging technologies to better understand stem cell biology in vitro and in vivo. For adult stem cells, we are interested in monitoring stem cell survival, proliferation, and differentiation. For embryonic stem cells, we are currently studying their tumorigenicity, immunogenicity, and differentiation. For induced pluripotent stem cells, we are working on novel derivation techniques. We also develop novel vectors and therapeutic genes for cardiovascular gene therapy applications.

Profile & Publications
http://wulab.stanford.edu/

Phillip Yang, M.D., CV Medicine 
Cardiovascular MRI. Clinical translation of novel MR imaging sequences. Molecularimaging of stem cells.

Potential research projects:
1) Cellular and molecular imaging of stem cell engraftment.
2) Novel cardiac MRI of myocardial perfusion and coronary arteries.

Profile & Publications

Vascular Growth, Structure and Disease

Julie Baker, Ph.D., Genetics 
Genetic determinants of vasculogenesis

Potential Research Projects:
Early Differentiation of Cardidomyocytes in vivo and in vitro. Embryonic stem cells offer the promise of therapies for a variety of cardiovascular diseases. One of the major caveats yet to be addressed is how to identify the earliest progenitors of cardiomyotes that emerge from undifferentiated ES cells. These progenitor cells will be important in future therapies simply because they are committed toward a cardiac lineage, but are likely still able to form multiple different cell types within that lineage. We have performed microarray analysis on serial stages of mouse post-implantation embryonic development and on mouse embryonic stem (ES) cells differentiating into cardiomyocytes. The former timecourse is described in the attached paper which we recently submitted to Nature Genetics. The later timecourse array is complete and encompasses a day by day analysis of cardiomyocyte differentiation beginning with undifferentiated mouse ES cells and concluding with beating cardiomyocytes which were then dissected into different cellular types. The major aim of these projects is to identify markers to elucidate early cardiac progenitor cells from differentiating ES cells. Here I outline several projects that could be completed as a requirement for Cardiovascular Medicine Concentration.
1. Aim: To identify the molecular program of cardiomyocyte differentiation and elucidate molecules that are expressed within cardiomyocyte progenitors. The computational analysis of the mouse ES differentiation array timecourse needs to be undertaken. The would entail elucidating the molecules that change significantly throughout cardiomyocyte differentiation with close attention paid to molecules being upregulated coincidently with the earliest markers for cardiomyocyte differentiation, including Nkx-
2. Aim: Identify new markers of early cardiac differentiation. We have elucidated several hundred molecules that are upregulated during the mouse embryonic stages when initial heart formation occurs. These molecules will be compared with adult heart restricted ESTs represented in Unigene. Any molecule that is upregulated during embryonic stages where heart development is occurring and is also represented only within the adult heart will be tested by in situ hybridization on early mouse embryos to elucidate whether it is also heart restricted during embryogenesis. We have thus far test 11 of these candidates and 3 are indeed heart restricted during early embryogenesis.
3. Aim: Human Embyronic Stem Cell (HESC) differentiation into cardiomyocytes. We now have HESCs growing robustly in our laboratory and are performing high throughput microarray and proteomic approaches on early differentiation of these cells. The differentiation protocol into human cardiomyocytes has yet to be successfully performed to homogeneity. This project would aim to generate human cardiomyotes at a high efficiency so that genomic technologies could be then used to elucidate the cardiac developmental program in humans.

Profile & Publications

Ronald L Dalman, M.D., Surgery - Vascular Surgery 
Biomolecular Imaging
The lab uses biocellular imaging techniques to follow the progression of abdominal aortic aneurysm disease in an animal model. We use MRI, PET CT , spectroscopy, and bioluminescence to image aneurysms created in rodents.

Potential research projects and scholarly papers for interested students involve learning the pathogenesis of AAA disease as an inflammatory process using one of these imaging modalities.

Profile & Publications

Andrew Connolly M.D., Pathology 
Vascular pathology and endothelial biology

Profile & Publications

Peter Kao, M.D., Ph.D., Pulmonary and Critical Care Medicine 
Mechanisms of pulmonary arterial hypertension.

Possible Projects: 
(1) Pathophysiologic studies of experimental pulmonary hypertension.
(2) Identification of lung stem/progenitor cells.
(3) Studies of lung surfactant rheology and the effects of cellular oxidative stress.

Profile & Publications

Fredric B. Kraemer, M.D., Endocrinology 
Cellular lipid metabolism

Potential original research projects:
1. Mechanisms regulating adipocyte lipolysis
2. Structural studies of hormone sensitive lipase

Potential scholarly research papers:
1. Interplay between adipogenesis (fat) and osteogenesis (bone)
2. Review of lipolysis

Profile & Publications

Calvin Kuo, M.D., Ph.D., Hematology 
Regulation of angiogenesis

Potential research projects:
1. Anti-angiogenic treatment of cancer using adenoviruses expressing soluble ectodomains of endothelial receptors (VEGFRs, PDGFRs, etc)
2. Physiologic effects of long-term blockade of VEGF and other angiogenic pathways 3. Exploration of a novel G-protein coupled receptor expressed in brain vasculature using knockout mouse and zebrafish models

Profile & Publications 
http://hematology.stanford.edu/research/kuo_lab.html

Stanley Rockson, M.D., CV Medicine 
1. Lymphatic Biology and Disease; 2. Preventive Cardiology; 3. Vascular Disease Mechanisms and Interventions

Potential research projects:
1. Molecular characterization of the pathogenesis of lymphatic vascular insufficiency: In our laboratory, we have been working on a model of lymphatic vascular insufficiency in the mouse tail, to simulate human lymphedema of the limb. In this model, we characterize histologic, immunohistochemical and molecular changes associated with the disease and its potential therapies. We utilize microarray and PCR to characterize the patterns of gene response to the functional insult. We are using this work as a platform to evaluate therapeutic lymphangiogenesis, as well as other pharmacologic therapies. Current projects related to this model include ongoing characterization of the responsiveness of the experimental disease to systemic anti-inflammatory therapies
2. Clinical translational studies are also underway to characterize the treatment response of human subjects to systemic anti-inflammatory therapy for lymphatic vascular insufficiency
3. Active research is underway to identify biomarkers for human lymphatic vascular insufficiency
4. In related research, we are also investigating the utility of VEGFR-3 receptor antagonism to prevent and treat experimental lymphangioma.

Potential scholarly papers:
1. A review of the mechanisms of cancer metastasis through the lymphatic system and the potential to develop therapeutic strategies to limit lymphatic metastasis
2. A review of the biology of inflammation, with special attention to the role of lymphatic system and immune traffic
3. A review of the biology of HDL-cholesterol and potential for therapeutics to reverse the cardiovascular risk of low HDL.

Profile & Publications

Philip S. Tsao, Ph.D., CV Medicine 
Basic and translational research investigating molecular mechanisms in vascular disease; insulin resistance syndrome; diabetes-related vascular and cardiac complications; biomechanical stimulation of endothelial cells

Potential research projects:
1. Differential gene expression induced by insulin resistance and diabetes.
2. Phenotypic characterization of a novel murine model of vascular stiffness.

Profile & Publications

Richard N. Zare, Ph.D., Chemistry
Bioanalytical chemistry

Potential research projects:
We wish to develop a method that allows for the simultaneous determination of minute amounts of ADMA, SDMA, and L-arginine as well as the enzymatic degradation product L-citrulline and the precursor for the biosynthesis of L-arginine and ADMA, L-ornithine in human plasma. Plasma concentrations for ADMA and SDMA are expected to be between 0.1 - 5 uM and those for L-arginine 50-100 uM. Of immediate interest is finding an antibody directed against ADMA, which interferes with NO synthetase and therefore is an important biomarker in cardiovascular disease states.


Profile & Publications 
www.stanford.edu/group/Zarelab

Christopher K. Zarins, M.D., Surgery/Vascular Surgery 
Artery wall adaptation and remodeling, and pathogenesis of aortic aneurysms.

Profile & Publications

Pulmonary Vascular Structure

Cristina M. Alvira, M.D., Pediatrics/Pulmonary and Critical Care Medicine

The main goal of the research ion the laboratory is to elucidate the molecular mechanisms that promote angiogenesis in the developing lung. A current focus is on the elucidation of  a novel, developmentally essential role for nuclear factor kappa-B (NFκB), a transcription factor previously associated with lung pathology.   We have found that NFκB is constitutively active in the neonatal pulmonary endothelium. Furthermore, blocking NFκB in neonatal mice decreases pulmonary capillary density and disrupts alveolarization in vivo, and decreases survival, proliferation, and angiogenesis of neonatal primary pulmonary endothelial cells (PEC) in vitro.  Current scientific goals within our laboratory are to:
1. Identify the mechanisms allowing for constitutive NFκB activity in the neonatal pulmonary endothelium; and
2. Elucidate how constitutively active NFκB promotes angiogenesis in the developing lung.
Elucidation of the upstream signaling pathways that induce this proangiogenic pathway in the neonatal pulmonary endothelium, and careful dissection of the beneficial (versus pathologic) downstream limbs of the pathway, will provide the necessary foundation for the development of targeted therapeutics to treat pediatric and adult diseases characterized by airspace loss and impaired angiogenesis, such as BPD and emphysema.

Profile and Publications

• David Cornfield M.D., Pediatrics / Pulmonary Biology 
  Regulation of vascular tone in the developing lung and oxygen sensing
  
  Research Projects:
  Our bench-based investigations are focused upon the developmental regulation of perinatal pulmonary vascular tone and upon oxygen sensing. In one set of studies, the laboratory works on the ion channel biology of pulmonary circulation in the developing lung. To address the issue of vascular tone we use microfluorimetry, patch clamping and whole animal physiology. The study questions are further informed by the use of selective molecular and pharmacologic probes. Through the development of physiologic and pathophysiologic models, we have been able to ask study questions in parallel systems. In a separate, but related line of investigation, we are studying the role of hypoxia-inducible factor 1 alpha in the developing pulmonary circulation. These experiments rely primarily on molecular tools to determine the mechanisms that account for the developmental regulation of the HIF-1 molecule.
  In addition, we are involved in the translational research wherein study questions that relate directly to patients can effectively addressed through an hypothesis driven approach. Recent examples of publications that have resulted from these efforts include the use of inhaled nitric oxide in children with acute hypoxemic respiratory failure or the appropriate use of a specific sedative-hypnotic agent in the Pediatric Intensive Care Unit setting.
  
  Profile & Publications
  
  Vinicio de Jesus Perez, MD, Pulmonary and Critical Care Medicine
  My research work is aimed at understanding how the following processes impact the development of abnormal vascular remodeling in Pulmonary Hypertension:
  1, Role of the Wnt signaling pathways in regulation of pulmonary angiogenesis: I am currently working with both in vitro and murine transgenic models to determine whether abnormalities in both canonical and noncanonical Wnt pathways may impact the function of BMP signaling in pulmonary endothelial cells and affect development of pulmonary hypertension.
  2. Role of Wnt signaling in smooth muscle growth and movement: I am using both in vitro and a tissue specific conditional SM22 transgenic mouse to explore the impact of BMPRII knockdown on SMC behavior and explore the role that both canonical and noncanonical Wnt signaling pathways play in this response. In addition, we want to explore how the immediate extracellular environment may contribute to increase the susceptibility of SMC to surrounding growth factors and promote their unrestricted growth.
  3. Role of BMPRI and II haploinsufficiency in PAH: Using a novel tamoxifen-CRE murine model, we will explore the contribution that dual reduction in expression of BMPRIa and II have on development of PAH. This work will also be complemented by use of genomic and molecular approaches to identify novel gene targets for future studies. 
  
  Profile and Publications
  
  Marlene Rabinovitch, M.D., Pediatric Cardiology 
  Pathobiology of pulmonary hypertension, transgenic models, gene therapy
  
  Sample research projects:
  Using induced pluripotent stem cell (iPSC) derived vascular cells as a personalized medicine approach to treatment of patients with pulmonary hypertension
• hjk
•  

Profile & Publications
http://med.stanford.edu/labs/rabinovitchbland/

Roham T. Zamanian, M.D., Pulmonary and Critical Care Medicine
Research Interests:
1. The Utility of S100A4/Mts1 as a Biomarker in Pulmonary Arterial Hypertension (PAH).
2. Prevalence and Treatment of Insulin Resistance in PAH.
3. The Effect of EGF-Receptor Blockade and Elastase Inhibitor on Pulmonary Arteries of Patients with PAH.
4. Characterization of Pulmonary Arteries in Patients with Idiopathic and Secondary PAH by Wedge Angiography.
5. The Optimal Angle for Angiographic Evaluation of the Left Pulmonary Artery in Patients with PAH.

Profile and Publications

Cardiovascular Development and Congenital Heart Disease

Daniel Bernstein, M.D., Pediatric Cardiology

Role of adrenergic receptors in regulating cardiotoxicity and cardioprotection; Interaction between cell signaling pathways during the development of cardiac hypertrophy; Long-term complications of pediatric heart transplantation; genomic influences on outcome in pediatric cardiac surgery

Profile & Publications

Richard D. Bland, M.D., Pediatrics/ Neonatology 
Lung development, neonatal lung injury and respiratory distress, lung fluid balance during development, pulmonary edema.

Potential research project:
Studies of lung structural changes associated with prolonged mechanical ventilation of newborn mice. This is part of a project that looks at the impact of cyclic lung stretch on genes that regulate lung growth and development.

Potential scholarly papers:
(1) Comprehensive review of what is known about fluid balance in the developing lung and its relationship to neonatal lung disease.
(2) Comprehensive review of what is known about the pathogenesis of neonatal chronic lung disease, also called bronchopulmonary dysplasia, which was first described at Stanford (1967) by Dr William Northway and associates.

Profile & Publications
http://med.stanford.edu/labs/rabinovitchbland/

Mark Krasnow M.D, Ph.D., Biochemistry 
Lung development from drosophila to mice

Profile & Publications

Richard Moss M.D., Pediatric Pulmonary Medicine and Allergy 
Translational research in cystic fibrosis Our group focuses on translational projects in cystic fibrosis, i.e. phase I-II studies of new therapies. Depending on time available the student would work with the research group (investigator, research coordinators, research assistants) in observing and helping with processes of protocol development, regulatory approvals, patient enrollment, protocol conduct, data entry and analysis, and preparation for presentation and publication.

Profile & Publications
http://cfcenter.stanford.edu

Daniel J. Murphy, M.D., Pediatric Cardiology 
Congenital heart disease in adults, echocardiography of congenital heart defects

Potential projects for the Scholars Track:
1. Review of the performance of the right ventricle or a single ventricle as a systemic pump. Focus on predictors of myocardial dysfunction.
2. Investigation and review of the finances and access to care for adults with congenital heart disease. This could also involve a descriptive project evaluating a business plan for care of this population.
3. Description of the psychosocial issues facing adult survivors of chronic childhood disease.

Profile & Publications

Marlene Rabinovitch M.D., Pediatric Cardiology 
Heart and blood vessel development

Sample research projects:
Using induced pluripotent stem cell (iPSC) derived vascular cells as a personalized medicine approach to treatment of patients with pulmonary hypertension

The epigenetics of induced pluripotent stem cell derived vascular cells and native vascular cells in patients with pulmonary hypertension

The role of amphetamines and DNA damage in transformation of pulmonary vascular cells

Profile & Publications
http://med.stanford.edu/labs/rabinovitchbland/

Norman Silverman, M.D., D.Sc., FACC, Pediatric Cardiology 
Echocardiographic determinants of heart function in congenital malformations, fetal echocardiography

Potential research projects (either original research or scholarly track):
1. Estimation of right ventricular volume by 2- and 3-dimensional echocardiography.
2. Estimation of Pulmonary regurgitation volume in tetralogy of Fallot using Echocardiography: Comparison with 3-dimensional echocardiography

Profile & Publications

Jeffrey J. Wine Ph.D., Psychology, and Director, Program in Human Biology 
Electrophysiological and optical methods to study the pathogenesis of cystic fibrosis airway disease

Potential research projects:
1. Determine if airway submucosal gland secretions play a role in protecting transplanted lungs from infection/rejection.
2. The role of airway submucosal gland secretions in cystic fibrosis lung disease. Potential scholarly papers:
1. White blood cells in healthy and diseased airways;
2. Role of VIP in controlling airway inflammation
http://www.stanford.edu/~wine/

Sean Wu, M.D., Ph.D., Cardiovascular Medicine

My research laboratory seeks to identify mechanisms responsible for human congenital heart disease, the most common cause of still-births in the U.S. and one of the major contributors to morbidity and mortality in infants and toddlers. We believe that by understanding the mechanisms regulating growth and differentiation of heart precursor cells during early embryonic development we can then apply these principles to understand the pathogenesis of adult onset heart diseases such as heart failure and arrhythmia where re-activation of early embryonic developmental program plays a central role. We currently use both genetically-modified mice as our living model to understand the biology of heart development as well as embryonic stem cells as a test-tube model to study the process of heart cell formation.

Profile and Publications

Electrophysiology and Rhythm Disturbances  

William Clusin, M.D., Ph.D., CV Medicine 
Cellular Cardiac Electrophysiology

Possible projects (Scholars Track):
1. Genetically mediated cardiac arrhythmias
2. Mechanisms of lethal arrhythmias in ischemic heart disease

Profile & Publications

Karen Friday, M.D, CV Medicine 
Clinical research in electrophysiology

Profile & Publications

Victor Froelicher, M.D., CV Medicine 
Emeritus Professor of Medicine working at VA Palo Alto VA, Stanford Hosp/Clinics Sports Cardiology clinic and Sports medicine clinic/Human Performance Lab (courtesy appointment Orthopedic Surgery)

Main interests:
Sports Cardiology, computerized electrocardiology, exercise physiology, test characteristics, sudden cardiac death
Projects for students include writing/reviews leading to scientific publication, analysis of clinical and test data from screening athletes, comparison of computerized ECG data between athletes and disease groups, performing pre-participation exams on athletes

Profile & Publications
https://scholar.google.com/citations?user=vvbF9OQAAAAJ&hl=en

Merritt Maduke, Ph.D., Molecular & Cellular Physiology 
Development of small-molecule inhibitors to treat hyponatremia
The chloride channels CLC-Ka and CLC-Kb play specific roles in the kidney. Inhibitors of CLC-Ka have promising therapeutic potential for treating and preventing hyponatremia. For this purpose, it is essential to have inhibitors specific for CLC-Ka over CLC-Kb, as the two channels play essential (but redundant) roles in hearing. In this project, we will build upon our discovery of a novel small-molecule CLC-Ka inhibitor. An iterative combination of site-directed mutagenesis, electrophysiology, double-mutant cycle analysis, and computational docking will be used to facilitate design and testing of next-generation inhibitors. Animal studies will be performed to validate the new drugs developed.

Projects Available:
1. Membrane-protein based screens for CLC-interacting proteins: Ion channel activity is often exquisitely modulated by the presence of tissue-specific accessory subunits. Many such subunits for the various cation-selective ion channels have been discovered and characterized, but thus far only one accessory subunit for the CLC chloride channels is known. The goal of this project is to take advantage of new methods of screening for membrane-protein interactions to discover and characterize candidate CLC-accessory subunits. Review article: Iyer K et al. (2005). Utilizing the split-ubiquitin membrane yeast two-hybrid system to identify protein-protein interactions of integral membrane proteins. Sci STKE. Mar 15; 2005(275):p13.
2. High-throughput screens for CLC inhibitors: Specific inhibitors of the CLC channels and transporters are sorely lacking. Such inhibitors would be invaluable for functional studies, and may also prove useful in the design of therapeutic agents targeting human CLCs. The goal of this project is to design high-throughput based on fluorescence assays we have developed in the lab, taking advantage of the facilities at the Stanford High Throughput Bioscience Center . Review article: Verkman AS (2004). Drug discovery and epithelial physiology. Curr Opin Nephrol Hypertens. 13(5)563-8. 3. 19F NMR to probe conformational changes in CLC proteins. (Call if interested).

Profile & Publications

Minang (Mintu) P. Turakhia, MD MAS
Director of Cardiac Electrophysiology,
Palo Alto VA Health Care System
Instructor of Medicine (Cardiovascular Medicine)

Efficacy, effectiveness, and cost-effectiveness of medical and device-based therapies for heart rhythm disorders. Access to multiple large datasets. Clinical projects will be used as a training vehicle to gain proficiency in clinical research methods, statistical methods, use of statistical software, data analysis, manuscript preparation, and presentation. Trainees are expected to be first authors and presenting authors for projects.

Potential projects:
1. Trends in treatment of atrial fibrillation (using national data from VA and Medicare)
2. Cardiac structural determinants of stroke risk in atrial fibrillation (using longitudinal cohort study data)
3. Electrocardiographic predictors of structural heart disease and clinical events

Profile & Publications

Paul Wang, M.D., CV Medicine 
Clinical electrophysiology and ablation

Profile & Publications

Cardiovascular Devices and Imaging

William Fearon, M.D., CV Medicine 
Investigating Coronary Physiology in the Cardiac Catheterization Laboratory

Potential research projects:
Determining the changes and factors that affect the changes in coronary physiology that occur in various settings, such as after cardiac transplantation, after acute myocardial infarction, and in the absence of epicardial coronary disease.

Potential scholarly papers:
Reviewing the major recent developments in the application of wire-based measurements of coronary physiology.

Profile & Publications

Peter FitzGerald, M.D., Ph.D., CV Medicine 
Intravascular Ultrasound

Profile & Publications 

Curtis W. Frank, Ph.D., Chemical Engineering/ Center on Polymer Interfaces an Macromolecular Assemblies (CPIMA) 
The interfacial properties of polymers used in cardiovascular devices. (Ideally, this would be in collaboration with someone from the School of Medicine .)
http://www.stanford.edu/group/cpima/cpima/stanfordresearch.html#frank

Sanjiv (Sam) Gambhir M.D., Ph.D., Radiology 
Molecular imaging

Possible projects: 
1) Image cell/molecular events in living subjects.
2) Develop molecular imaging probes targeted for specific events.
3) Translate molecular imaging assays into the clinic.

Publications: 
S.S. Gambhir, D. Berman, J. Ziffer, M. Nagler, M. Sandler, J. Patton, B. Hutton, T. Sharir, S. Haim.  A Novel High-sensitivity Rapid-acquisition Single-photon Cardiac Imaging Camera. Journal of Nuclear Medicine, 50(4): 635-643, 2009.

M. Rodriguez-Porcel, O. Gheysens, R. Paulmurugan, I. Chen, K. Peterson, J. Willmann, J. Wu, X. Zhu, L. Lerman, S.S. Gambhir. Antioxidants Improve Early Survival of Caridomyoblasts after Transplantion to the Myocardium. Molecular Imaging and Biology, 2010 Jun;12(3):325-34.

Profile & Publications 
http://mips.stanford.edu/

Michael Goris, M.D., Ph.D., Radiology 
Cardiac PET/SPECT

Current research projects:
1. Display of myocardial motion by projecting specific components of the 3D motion of myocardial elements on the plane of origin
2. A natural language automated reporting system for Myocardial Perfusion scintigraphy:
Myocardial perfusion scintigraphies can be analyzed quantitatively, but the difficulty is to translate the quantitative metric into clinical relevant phraseology. A system translating picture analysis into clinical description is being tested. Presently the picture analysis output is entered after visual interpretation of a quantitative output, but the goal is to go directly from elementary image metric to clinical interpretation.

Profile & Publications

David Lee, M.D., CV Medicine 
Interventional cardiology and devices

Current Research Projects:
1. Novel pharmacologic and device adjuncts in the treatment of acute myocardial infarction
2. Implications of anatomy and risk factors for post-PCI myocardial infarction
3. Outcomes of treatments for hypertrophic cardiomyopathy

Profile & Publications

A.C. Matin Ph.D., Microbiology & Immunology 
Bacterial biofilms in cardiovascular disease and devices

Potential projects:
Original Research Track: Precise role of specific bacterial genes (that we have identified) in conferring resistance on biofilms to antibiotics. (We have several mutants in Staphylococcus aureus, whose biofilms cause endocarditis, that fail to increase resistance in biofilm state. We know what genes are affected and are investigating their role in resistance.)
Scholars Track: Bacterial biofilms studied in-situ (ie in affected organs themselves).

Profile & Publications 
http://www.stanford.edu/~amatin/MatinLabHomePage/MatinLabHome-Page.htm

Michael McConnell, M.D.,MSEE, CV Medicine 
MR imaging of cardiac structures
(Available to mentor students in the Scholarly Track)

Profile & Publications 
http://www.stanford.edu/group/skmlab/

Drew Nelson Ph.D., Mechanical Engineering
Engineering design, devices
New or Improved Device or Surgical Instrument for Use in CVP
Main Elements:
(1) Research and identify potential opportunities for new or improved CVP surgical instruments or implanted devices;
(2) Become familiar with and prepare an overview of technological advances offered by engineering that may potentially be relevant to CVP (e.g., smart materials, new sensory capabilities, etc.);
(3) Evaluate the opportunities in view of what was learned in part (2) and select one opportunity to pursue;
(4) Generate concepts for a new or improved device or instrument and collaborate in development of a working model;
(5) Perform initial testing of the model, and
(6) Report the results of the project in a journal publication.
That may be too ambitious, but could be adjusted if it's of interest to anyone and within the scope of what would be acceptable for the program.

Profile & Publications

Terry Robinson, M.D., Pediatric Pulmonary Medicine 
3D CT airway/lung segmentation & quantitative airway and regional air trapping analysis, Functional chest CT imaging in the pathogenesis of cystic fibrosis and other obstructive lung diseases.

Profile & Publications

Norman Silverman, M.D., Pediatric Cardiology 
Echocardiographic determinants of heart function in congenital malformations, fetal echocardiography

Potential research projects (either original research or scholarly track):
1. Estimation of right ventricular volume by 2- and 3-dimensional echocardiography.
2. Estimation of Pulmonary regurgitation volume in tetralogy of Fallot using Echocardiography: Comparison with 3-dimensional echocardiography

Profile & Publications

Joseph Wu M.D., Ph.D., CV Medicine and Radiology 
Our lab studies the biological mechanisms of adult stem cells, embryonic stem cells, and induced pluripotent stem cells. We use a combination of gene profiling, tissue engineering, physiological testing, and molecular imaging technologies to better understand stem cell biology in vitro and in vivo. For adult stem cells, we are interested in monitoring stem cell survival, proliferation, and differentiation. For embryonic stem cells, we are currently studying their tumorigenicity, immunogenicity, and differentiation. For induced pluripotent stem cells, we are working on novel derivation techniques. We also develop novel vectors and therapeutic genes for cardiovascular gene therapy applications.

Profile & Publications
http://wulab.stanford.edu/

Phillip Yang, M.D., CV Medicine 
Cardiovascular MRI
1) Cellular and molecular imaging of stem cell engraftment. Novel cardiac MRI of myocardial perfusion and coronary arteries.
2) First publication of cellular MRI of stem cells at 1.5T. Real-time coronary MRI.

Profile & Publications

Alan Yeung, M.D., CV Medicine 
Human coronary physiology

Profile & Publications

Paul Yock, M.D., CV Medicine 
Device development, tissue engineering
Note:Dr. Yock is not available to mentor in the Winter ofr Spring of 2006

Profile & Publications 
http://biox.stanford.edu/clark/yock.html

CVP Exercise Physiology, and Risk Factors of CVP Disease

Paul Heidenreich, M.D., CV Medicine 
Cost-effectiveness of therapies for myocardial ischemia and congestive heart failure; Quality of Care and Outcomes Research for Heart Disease.

Potential Projects:
1. Trends in the treatment and outcome of heart failure. This study uses national data from the VA health care system.
2. Impact of valve disease on prognosis. This study uses data from a large echocardiography database.

Profile & Publications

Mark Hlatky, M.D., Health Research & Policy 
Outcome studies of CV disease

Profile & Publications

Jonathan Myers, Ph.D., CV Medicine (Palo Alto VA)
Clinical exercise physiology; Cardiopulmonary exercise testing; Epidemiology / cardiovascular health

Potential Projects:
1) Interaction between obesity and physical activity patterns in predicting mortality
2) Comparison between chronotropic incompetence, heart rate recovery, and the Duke Treadmill Score in predicting cardiac events

Profile & Publications

Gerald Reaven, M.D., CV Medicine 
Insulin resistance, obesity, hypertension diabetes, cardiovascular disease

Potential Research Projects
1) Relationship between adipocyte cell size and number, insulin resistance, and cardiovascular disease
2) Metabolic effects on weight, insulin action, insulin secretion and cardiovascular disease risk in patients taking atypical antipsychotic drugs

Potential Scholarly Papers
1) Is obesity the cause or simply a modulator of insulin resistance and associated abnormalities

Profile & Publications

Randall Stafford, M.D., Ph.D.
Associate Professor of Medicine
Director, Program on Prevention Outcomes and Practices
Stanford Prevention Research Center

Research Interests:
Delivery of prevention services, quality of care, chronic disease management, health disparities, pharmaceutical regulation, and comparative effectiveness research.

Potential Projects:
1) Investigate national changes in physician prescribing for hypertension, diabetes, and hyperlipidemia.

2) Analyze the association of cardiovascular risk factors with each other and social factors in a cohort of Latina and Latino patients with obesity.

Publication:
Stafford RS, Bartholomew LK, Cushman WC, et al.  Impact of the ALLHAT/JNC7 Dissemination Project on Thiazide-Type Diuretic Use.  Arch Intern Med; 2010; 170: 851-858.  PMID: 20498411

Profile & Publications

Marcia Stefanick Ph.D., I think so Medicine/SPRC 
Cardiovascular Disease Prevention: Lifestyle (Exercise, Weight Control, Diet) and Menopausal Hormones

Profile & Publications
Stanford Prevention Research Center

Anne Dubin, M.D., Pediatric Cardiology
Resynchronization clinical trials

Frank Hanley, M.D., Pediatric Cardiothoracic Surgery
Surgery of complex cardiac malformations in the neonate, fetal surgery

Rex Jamison M.D., Nephrology
Homocysteine and vascular disease

Gregory Kovacs M.D. Ph.D., Electrical Engineering
Devices for pharmaceutical screening, pacing, genomics

Tom Quertermous, M.D., CV Medicine
Angiogenesis and molecular vascular biology

Mohan Reddy, M.D., Pediatric Cardiothoracic Surgery
Complex cardiac surgery in premature and low birth weight neonates and single ventricle physiology

R. Kirk Riemer Ph.D., Surgery
Cardio-pulmonary physiology and pulmonary arteriovenous malformations

Patrick, O. Brown, M.D., Ph.D., Biochemistry
Use of DNA microarrays to watch genomes in action. Systematical characterization of the genetic script that controls gene expression in healthy cells and disease.

Mark A. Kay, M.D., Ph.D., Pediatrics (Genetics)
Gene transfer technologies and gene therapy for genetic and acquired diseases. Viral and non-viral vector systems in hemophilia and hepatitis C virus infection.

Philip Lavori, Ph.D., Health Research and Policy
Biostatistics, clinical trials.

Richard M. Myers, Ph.D., Genetics
Molecular basis of human inherited diseases and traits, including Huntington disease, Parkinson disease, schizophrenia, insulin resistance, atherosclerosis and hypertension; genetic analysis of human protocadherins; genome analysis, large-scale genomic and full-length cDNA sequencing, genome-wide analysis of human transcriptional regulation.

Garry P. Nolan, Ph.D., Microbiology and Immunology
Signaling in the immune system. Autoimmunity, angiogenesis, retrovirology, and HIV-1,using Flow Cytometry (FACS) of phosphoprotein activation states in single cells, a range of viral cDNA/peptide expression systems and single-cell genetic selections.

Roeland Nusse, Ph.D., Developmental Biology
Function of Wnt proteins during embryogenesis and in cellular processes in Drosophila and in mammals.

Norbert J Pelc, Sc.D., Radiology and Bioengineering (Electrical Engineering) 
Phase contrast MRI to separate moving from static structures, to visualize 3D motion of the heart to evaluate heart function, coronary and cerebral blood flow.

Thomas A Rando, M.D., Ph.D., Neurology and Neurological Sciences VA/PAHCS
Postnatal myogenesis; Gene therapy for muscular dystrophies; Pathogenetic mechanisms in muscular dystrophies; Cellular and molecular mechanisms of age-related muscle atrophy.

Robert J. Tibshirani, Ph.D., Health Research and Policy (Statistics)
Applied statistics and biostatistics, analysis of genomic data and imaging data

Irving L. Weissman, M.D., Ph.D., Cancer Biology Pathology, Developmental Biology (Biological Sciences
Development of T and B lymphocytes; cell-surface receptors for oncornaviruses in leukemia. Hematopoietic stem cells; Lymphocyte homing, lymphoma invasiveness and metastasis.