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The Pediatric Cardiology Physician-Investigator Pathway
UCSF is one of the world’s leading centers for biomedical research. Trainees can draw on the expertise of world-renowned investigators within the Pediatric Heart Center and in other UCSF departments and research units. Applicants are encouraged to access the Biomedical Sciences Graduate Program, the UCSF Cardiovascular Research Institute, the UCSF Institute for Regeneration Medicine, and the Gladstone Institute for Cardiovascular Disease websites to explore the breadth and depth of this strong institutional commitment to basic and translational investigation in human diseases, and the range of potential mentors with whom they may pursue research training. Researchers at the Pediatric Heart Center are performing state of the art research in congenital and acquired pediatric heart disease. Major efforts involve investigating the genetic basis of congenital heart disease, genetic and epigenetic control of cardiac development, regulation of cardiac myogenesis and the use of stem cells for myocardial repair. Clinical studies focus on the use of new imaging modalities and invasive techniques for the diagnosis and management of pediatric cardiovascular disease, as well as outcome studies in patients treated for congenital heart defects. The Division is strongly committed to training the next generation of academic physician-investigators. As evidence of this commitment the Division has an NIH-funded T32 for Training in Developmental Cardiovascular Biology to specifically support fellows interested in combining clinical training in pediatric cardiology with scientific training in cardiovascular research. This grant has supported dozens of fellows over its more than 20 year history, many of whom have gone on to be academic leaders and division chiefs at other institutions. In addition, the Division has supported fellows through the Pediatric Scientist Development Program, a program sponsored by the Association of Medical School Pediatric Department Chairs. Trainees who pursue the physician-investigator pathway complete the requirements for clinical training during the first 15-18 months of fellowship, followed by a 2-3 year block of protected research time. While fellows complete the requirements for board eligibility by the end of 3 years, most choose to continue with their research training beyond this time frame. A fourth year is supported either by the Division through the training grant or the fellow’s research advisor, and support beyond that is by arrangement with the fellow’s research advisor, although most fellows have obtained independent postdoctoral fellowship support by that time. Fellowship applicants interested in this pathway should forward a statement of interest, and a list of 3-5 UCSF investigators with whom they would like to meet during the interview day, to Dr. Harold Bernstein at the time of application submission. Questions about the Pediatric Cardiology Physician-Investigator pathway should also be directed to Dr. Bernstein.
A Tradition of Training Academic Leaders (Past Trainees)
The following is a list of core Pediatric Heart Center faculty with active research programs. However, trainees in the Pediatric Cardiology Physician-Investigator pathway are encouraged to explore research opportunities with any member of the UCSF faculty who has an appropriate research program, including faculty in the Biomedical Sciences Graduate Program, the UCSF Cardiovascular Research Institute, the UCSF Institute for Regeneration Medicine, and the Gladstone Institute for Cardiovascular Disease.
Dr. Harold S. Bernstein is Professor of Pediatrics (Cardiology), a Senior Investigator of the Cardiovascular Research Institute, and a member of the Institute for Regeneration Medicine, the Institute for Human Genetics and the UCSF Comprehensive Cancer Center. Dr. Bernstein also is the Principal Investigator and Director of the NIH-funded Training Program in Developmental Cardiovascular Biology, and Associate Director of the Pathway to Discovery in Molecular Medicine Program at the UCSF School of Medicine. Dr. Bernstein’s honors have included the Richard Rowe Award from the Society for Pediatric Research, the Young Investigator Award from the Heart Failure Society of America, the Ross Research Award from the Western Society for Pediatric Research, the Melvin Grumbach Research Award and Innovation in Basic Science Award from UCSF, and election to the Society for Pediatric Research. His laboratory studies the development, function and regeneration of skeletal and cardiac muscle, and also is pursuing the identification of novel biomarkers for heart failure in patients with congenital heart disease. See More >>Dr. Benoit G. Bruneau is Associate Professor of Pediatrics (Cardiology) at UCSF and Associate Investigator at the Gladstone Institute for Cardiovascular Disease, where he holds the William H. Younger Family Chair in Cardiovascular Research. Dr. Bruneau’s research is centered around the regulation of heart development by transcription factors and epigenetic regulators of chromatin. See More >>Dr. Jeffrey Fineman is Professor of Pediatrics (Critical Care), and Senior Investigator of the Cardiovascular Research Institute at UCSF. He is the recipient of numerous honors and awards including the John J. Sampson Award in Research from the American Heart Association. He is an active member of the Western Society for Pediatric Research, the Society for Pediatric Research, the Society of Critical Care Medicine, and the Pediatric Cardiac ICU Society. In addition, he is an Associate Editor of Pediatric Critical Care Medicine, a member of the Scientific Advisory Committee for the NIH K12 in Pediatric Critical Care, Research Director for the Pediatric Cardiac ICU Society, and a member of the RIBT NIH study section. Dr. Fineman’s research program studies the regulation of pulmonary blood flow and pulmonary vascular resistance in the normal and abnormal fetal, transitional, and postnatal circulations. See More >>Dr. Patrick McQuillen is Associate Professor of Pediatrics (Critical Care) at UCSF. Dr. McQuillen’s active basic and clinical research programs focuse on mechanisms of selective vulnerability and plasticity following injury to the developing brain. Laboratory research employs molecular, cellular and functional imaging techniques to study small animal brain injury models. Clinical research focuses on the application of advanced magnetic resonance brain imaging to understand neurodevelopmental outcome in infants requiring surgery for congenital heart disease. See More >>Dr. Alison Knauth Meadows is Assistant Professor of Pediatrics (Cardiology) and Radiology at UCSF. Dr. Meadows’ research activities are divided between 1) computation modeling of the cardiovascular system based on cardiac MRI and validated by traditional hemodynamics, and 2) investigating the efficacy of a model to transition adolescents and young adults with complex congenital heart disease from pediatric to adult-centered care. See More >>Dr. Phillip Moore is Professor of Clinical Pediatrics (Cardiology) and director of the Congenital Interventional Catheterization Program at UCSF, specializing in minimally invasive catheter treatment of congenital heart disease in both children and adults. His current areas of research include the development of intravascular suturing techniques, single ventricle interventional strategies, and interventional MRI. See More >>Dr. Kathleen Ruppel is Assistant Professor of Pediatrics (Cardiology). Dr. Ruppel’s lab studies the role of G-protein coupled receptor signaling pathways in vascular and cardiac development. See More >>Dr. Deepak Srivastava is the Director of the Gladstone Institute of Cardiovascular Disease, Professor of Pediatrics (Cardiology) and Biochemistry and Biophysics, and Wilma and Adeline Pirag Distinguished Professor in Pediatric Developmental Cardiology at UCSF. Dr. Srivastava has received numerous honors and awards, including endowed chairs at both the University of Texas Southwestern and UCSF, as well as election to the American Society for Clinical Investigation and the Society for Pediatric Research. Dr. Srivastava’s lab studies the molecular events regulating early and late developmental decisions that instruct progenitor cells to adopt a cardiac cell fate and subsequently fashion a functioning heart. See More >>Dr. Sarah Tabbutt is Associate Professor of Clinical Pediatrics (Cardiology and Critical Care) at UCSF and director of the Pediatric Cardiac Intensive Care Unit. Dr. Tabbutt’s research interests include clinical trials in the PCICU, neurodevelopmental outcomes in patients with congenital heart disease, and post-operative management of staged repair in patients with hypoplastic left heart syndrome. See More >>
1) To study the cell cycle withdrawal program in skeletal and cardiac myocytes, the Bernstein lab has developed methods for differentiating rodent and avian myoblasts into myocytes with spontaneous contractile activity, and for establishing and manipulating primary myoblast cultures. Using microarrays, they have identified several regulatory proteins that are differentially expressed in proliferating myoblasts versus post-mitotic myotubes. They have demonstrated that one of these proteins, Stem cell antigen-1 (Sca-1), specifically regulates the proliferation/differentiation transition during skeletal myogenesis. Current efforts in primary myoblasts and mouse models are focused on determining the mechanisms by which Sca-1 specifically controls myoblast proliferation and regulates myogenic precursor cell self-renewal. 2) To examine the regulation of human cardiac fate determination, the lab is identifying human embryonic stem cells (hESCs) that preferentially differentiate into cardiomyocytes, and developing methods for isolating developmentally-synchronized hESC-derived myocardial precursors. This will facilitate efforts to determine the contributions of genetic programming and environmental stimuli to subspecialization of human cardiomyocytes into atrial and ventricular myocardium, and conduction tissue. In collaboration with Dr. Srivastava’s group, they also are examining the role of microRNAs in cardiac fate determination in hESCs. 3) The Bernstein lab has demonstrated that hypertrophic stimuli cause a transient burst of Cdk4 activity, remodeling of the retinoblastoma protein complex, and activation of a subset of E2F-1 target genes in murine myoblasts. This has led them to identify a physiological role for both E2F-1-mediated activation and repression of genes involved in cell growth versus division, respectively. Currently, they are investigating the mechanism(s) by which Cip1/Kip1 and INK4 classes of Cdk-inhibitors facilitate this burst of Cdk4 activity, and the role of chromatin remodeling in the hypertrophic response. 4) Over the past several years, the identification of heterogeneous populations of muscle stem cells in the heart and bone marrow has generated great enthusiasm for new approaches to muscle repair and regeneration. However, these studies also have exposed the limitations of current strategies. Taking cues from the highly plastic, developing human heart, the Bernstein lab is exploring hESC-based therapies for heart failure. Using a mouse model of myocardial injury and cell delivery, they are determining the developmental stage at which hESC-derived myocardial cells engraft in vivo, and examining the effects of hESC transplant therapy on cardiac function. 5) To complement their efforts toward cell-based therapies for heart failure, the Bernstein lab also is investigating better ways to monitor heart failure and the response to therapy in children with single ventricle heart disease, the most difficult congenital heart defect to manage. They have initiated a human research protocol to measure the levels of four proteins found in blood in children with single ventricle compared to children with structurally normal hearts, to determine whether any of these potential biomarkers predict the presence or degree of heart failure in these children. Future efforts will be directed toward using proteomics to establish biomarker arrays for pediatric heart failure. For additional information on the Bernstein lab, please visit the website. Click here for a list of recent publications.
Dr. Bruneau’s group has been studying several transcription factors that pattern the developing heart using the mouse as a model organism. As several of these transcription factors have been identified as mutated genes in human CHD, their investigations have served also to understand how CHDs arise. For example, their studies of the T-box transcription factors gene TBX5, which when mutated causes CHDs in the context of Holt-Oram syndrome, have uncovered an important patterning role for Tbx5 in ventricular septation, and in the function of the conduction system. They have also defined biochemical interactions between Tbx5 and its transcriptional partners, the homeodomain transcription factor Nkx2-5 and the Spalt family transcription factor Sall4. Both are also mutated in human CHD, thus establishing an important link between these factors and providing an explanation about why mutations in these distinct genes cause similar CHDs. The Bruneau lab has also been investigating how transcription factors expressed in later stages of heart development are important for setting up critical aspects of heart function. These studies have come from investigating the Iroquois homeobox (Irx) family of transcription factors. Mice lacking single Irx genes have postnatal phenotypes that have illuminated key aspects of postnatal physiology that are eminently relevant to human disease, while combined gene deletions have uncovered more profound effects on heart morpogenesis. One of the most recent and exciting avenues of research in the Bruneau lab is the role of chromatin remodeling complexes in heart formation. They found that a component of the Swi/Snf-like BAF chromatin remodeling complexes, Baf60c, is expressed predominantly in the developing heart and is important for heart development. This has opened up a new avenue for the lab, one that has refocused them on the study of chromatin remodeling in heart development. This is one of the most exciting lines of research in heart development and organogenesis. Since the relationship between chromatin remodeling complexes and DNA-binding TFs is so finely regulated, the Bruneau group hypothesized that in non-cardiac cells it might be rate-limiting, explaining the inability of cardiac TFs to induce cardiac genes in non-cardiac cells. Indeed they have overcome this limitation to induce cardiac genes in non-cardiac cells and ectopic beating heart tissue in transfected cultured mouse embryos. This is the first demonstration that cardiac genes can be activated de novo in non-cardiac cells, and also the first instance of fully induced cardiogenesis in the mouse embryo. Thus, they have demonstrated that the relationship between DNA-binding TFs and chromatin remodeling complexes is at the root of the fine tissue-specific regulation of heart-specific gene expression, and that this could be harnessed to create new cardiomyocytes de novo. For additional information on the Bruneau lab, please visit the website. Click here for a list of recent publications.
More recently, he has investigated the effects of these endothelium-derived vasoactive factors in the injured pulmonary circulation, and have been interested in the potential role of aberrant endothelial function and oxidant stress in the pathophysiology of pulmonary hypertensive disorders. To this end, he has developed animal models of congenital heart disease to investigate the role of endothelial dysfunction in the pathophysiology of pulmonary hypertension secondary to increased pulmonary blood flow. In addition, he has been investigating the endothelial regulation of vascular tone following acute surgically-induced increases in pulmonary blood flow, the alterations in endogenous endothelial function during exogenous NO-cGMP exposure, and the mechanisms of the elevation in pulmonary vascular resistance and increased pulmonary vascular reactivity following cardiopulmonary bypass. Dr. Fineman’s clinical research interests focus on improving the peri-operative care of newborns, infants, and children with congenital heart disease. To this end, he has been investigating the potential use of B-type natriuretic peptide (BNP), a powerful biomarker of cardiac performance, to predict clinical outcomes in these children, with the ultimate goal of using serial BNP measurements to improve the clinical risk stratification, management, and outcomes for infants and neonates with CHD. Click here for a list of recent publications.
For example, MRI studies of premature infants identified a unique pattern of subcortical injury, very different from the injury pattern seen in babies born at term. Analysis of an animal model of very early hypoxic-ischemic brain injury discovered selective vulnerability of subplate neurons, a transient population of neurons required for the formation and plasticity of connections between thalamus and cortex. To understand this vulnerability, the McQuillen group is presently studying purified cultures of subplate neurons to develop novel age-specific neuroprotective therapies. They are using similar MR imaging techniques to study babies with congenital heart disease before and after they undergo surgery to correct their heart defects. Despite tremendous advances in the surgical procedures to repair heart defects, babies with congenital heart disease remain at high risk of brain injury. The McQuillen lab has observed that this brain injury may occur before, during or after surgery. In one example, they identified a life-saving procedure, atrial septostomy, as being associated with brain injury in over 60% of cases. They are currently devising clinical trials to make this necessary procedure safer. The developing brain is unique from the adult brain in both mechanism of injury, but also the capacity for repair and regeneration. These important differences require the development of novel treatments specific for the developing brain. For additional information on the McQuillen lab, please visit the Neonatal Brain Disorders and Cardiac MRI websites. Click here for a list of recent publications.
Dr. Meadows has a collaborative relationship with David Saloner, Ph.D., Liang Ge, Ph.D., and Julius Guccione, Ph.D. to integrate computational models of the aorta (Computational Fluid Dynamics) and of the myocardium (Finite Element Analysis) to investigate ventriculo-arterial coupling. Model parameters are obtained from cardiac MRI; some parameters obtained from standard imaging sequences such as geometry from 3D MRA and volumetrics from cine imaging; other parameters require highly specialized pulse sequences such as 7 and 1-dimensional flow and myocardial tagging techniques. Dr. Meadows is currently using her model to compare ventriculo-arterial coupling in patients with coarctation of the aorta compared to controls and validating her findings with standard hemodynamic data obtained in the catheterization laboratory. The computational model will then be used to predict changes in afterload with the address of recurrent or native obstruction. More broadly, the ultimate goals are to develop and validate a computational model that will permit noninvasive characterization of dynamic afterload and its impact on myocardial performance in healthy and disease states, and to predict response to intervention (catheter-based, surgical, or medical). Such a tool holds particular relevance for the emerging population of adults with complex congenital heart disease (ACHD), in whom ventriculo-arterial coupling remains poorly understood. Dr. Meadows also studies the process of transition in adolescents and young adults with complex Congenital Heart Disease. The impetus for such research is based on the fact that the number of adults with congenital heart disease is growing exponentially. These patients will ultimately transfer from pediatric to adult care. Given the typical absence of formal transition to guide this process, there is often delayed or inappropriate care, improper timing of transfer, and undue emotional and financial stress on patients, families, and the health care system. Dr. Meadows has postulated that a collaborative, interdisciplinary, formal transition program can provide the appropriate developmental, educational, and experiential process necessary to prepare these young adults to take responsibility for their own health and lives. Dr. Meadows has developed and implemented a formal transition program at UCSF to aid in the transition and transfer from pediatric to adult-centered care. She has developed a program of research to formally evaluate its efficacy. Using a quasi-experimental untreated control group study design with pre-test and post-test, she is testing the efficacy of this program by comparing self-care agency, knowledge, and high-risk behavior avoidance with an age and gender matched control group of young adults who transferred directly to an adult congenital heart disease program without participating in formal transition. The goal is for the UCSF congenital heart disease transition program, evaluated herein, to serve as a model for transition programs across the country. Click here for a list of recent publications.
Click here for a list of recent publications.
Click here for a list of recent publications.
Researchers in Dr. Srivastava’s laboratory have elucidated a cascade of transcriptional, translational and signaling events that control the early steps of cardiomyocyte differentiation and expansion. Human genetics has been used to discover the cause of some human cardiac septal defects and valve diseases, and revealed the mechanisms through which mutations in these genes result in anomalies. One of the developmental genes has potent properties for cardioprotection and is moving into clinical trials with patients suffering ischemic damage to the heart. Most recently, Dr. Srivastava has investigated the role of microRNAs in finely regulating the intricate events of cardiogenesis. MicroRNAs are genomically encoded small noncoding RNAs that target mRNA sequences for degradation or translational inhibition. Findings reported by Dr. Srivastava’s group revealed that microRNA1 (miR-1), one of the most conserved of the approximately 400 known microRNAs, was specifically expressed in developing heart and skeletal muscle progenitors and was transcriptionally activated in these regions by well-known regulators of differentiation, including serum response factor (SRF) in the heart, and MyoD along with Mef2 in the skeletal muscle. The Srivastava lab demonstrated that in mice miR-1 can directly regulate Hand2 protein levels and, when over expressed, could decrease cardiomyocyte proliferation in fetal hearts. Regulation of the balance between proliferation and differentiation is consistent with miR-1 being downstream of regulators of muscle differentiation. Correspondingly, they showed that Drosophila embryos lacking miR-1 had a defect in maintaining muscle gene expression and that Drosophila miR-1 was involved in differentiation of early mesodermal cells into cardiac cells in part by regulating the Notch signaling pathway. These findings implicated microRNAs in cardiomyocyte lineage determination and differentiation and have led to studies in the Srivastava lab showing that miRNAs can be used to promote cardiomyocyte formation rather than neuronal differentiation in mouse and human embryonic stem cells. For additional information on the Srivastava lab, please visit the website. Click here for a list of recent publications.
Click here for a list of recent publications.
Research Resources and Programs The Molecular Medicine Training Program The Molecular Medicine Training Program offers post-residency research training positions for physicians in the fields of Internal Medicine, Pediatrics, Dermatology, Laboratory Medicine and Pathology, who are committed to a career in basic or translational biomedical research. The goal of this program is to provide advanced training in the experimental study of the molecular and cellular basis of disease. This is done through individual laboratory research, lectures, seminars and journal clubs. In addition, through an individual advisory/mentoring system, the program provides guidance and advice about the practicalities of pursuing a career at the interface of science and medicine. Fellows enrolled in the program frequently take courses offered by the Graduate Division at UCSF. The program sponsors a weekly conference on disease-related science for members still in clinical residency or fellowship. This series includes research presentations by UCSF physician-scientists in both basic and clinical departments, as well as a journal club highlighting recent published advances in disease-related science. While official entry into the Molecular Medicine Training Program occurs at intern selection or during the first year of residency training at UCSF, any post-residency trainee is welcome to participate in the lectures, seminars and journal clubs offered by the program. The Pathway to Discovery in Molecular Medicine The Pathway to Discovery in Molecular Medicine program was developed in 2007 by the UCSF School of Medicine as a training opportunity and career-support framework in which students, residents and fellows are helped to envision a “career path forward” in academic medicine that combines clinical practice and disease-oriented laboratory research. For students, the primary goal is to provide a foundation of course work and an intensive laboratory research experience with a carefully chosen mentor and role model. For post-graduate trainees, the primary goal is to “keep the flame of research interest burning” as they complete their graduate clinical training and embark on basic laboratory research training. The core elements of the Pathway include a Summer Camp held in August to introduce trainees to basic techniques in cell and molecular research, including wet lab and bioinformatics approaches, didactic coursework in Cell Biology, Genetics and Macromolecules, elective coursework in a wide ranging set of biomedical topics, supervised research, and career mentoring. Fellows may take advantage of all aspects of the pathway. Advanced Training in Clinical Research Advanced Training in Clinical Research is a three academic quarter program intended for post-doctoral fellows and faculty members who desire rigorous training in the methods and conduct of clinical research. This includes instruction in the epidemiologic and biostatistical methods used in observational and experimental clinical research as well as training in the oral and written presentation of clinical research. In addition to required coursework, scholars are expected to develop and implement their research projects throughout the year and will have access to program faculty for methodologic guidance. Trainees achieving program objectives are granted a Certificate of Program Completion. UCSF Clinical Translational Science Institute (CTSI)/Pediatric Clinical Research Center The Pediatric Clinical Research Center (PCRC) is a child-oriented research organization within the institution-wide UCSF Clinical and Translational Sciences Institute (CTSI). As part of the unified infrastructure of the CTSI Clinical Research Centers, the PCRC is dedicated to clinical investigation focused on infants and children. The PCRC encompasses three research units: 1) a discrete, five-bed inpatient facility located within the UCSF Children’s Hospital staffed by professional research nurses; 2) an adjacent outpatient clinic which provides nursing and infrastructure for outpatient studies; and 3) a specialized research outreach team to carry out studies in the Intensive Care Nursery and Pediatric Heart Center. The PCRC is supported by a full-time child developmental psychologist, bionutrition services, a specialized core laboratory, a biostatistician to assist with study design and a computer systems manager. Members of the PCRC Advisory Committee are available to assist with study planning, and the PCRC Protocol Coordinator is a source for general information. Current CTSI/PCRC protocols being conducted by our faculty include:
Applying to the Pediatric Cardiology Physician-Investigator Pathway Fellowship applicants interested in this pathway should forward:
to Dr. Harold Bernstein at the time of application submission. Additional questions about the pathway should also be directed to Dr. Bernstein.
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Dr. Bernstein’s laboratory studies the mechanisms regulating cell division, and how such processes play a role in cardiovascular biology and disease. To this end their work has focused on three main areas of basic investigation: 1) mechanisms of cell cycle withdrawal during muscle differentiation; 2) cardiac fate determination in myogenic stem cells, and; 3) the role of cell cycle machinery in cellular hypertrophy. In addition, they recently have initiated two new areas of translational and clinical research that apply their understanding of how muscle cells behave to the development of new diagnostic and therapeutic approaches to heart failure: 4) human embryonic stem cell-based therapies for heart failure; and 5) identification of biomarkers of heart failure in patients with congenital heart disease.
Organogenesis requires the integration of transcriptional inputs to coordinate complex gene expression programs in differentiating cells. Lineage-committed precursor cells differentiate into a completely new cell type, thus requiring the de novo deployment of an entire cell-specific gene expression program. Concomitantly, organs also undergo morphogenesis to form more complex structures as development proceeds. The Bruneau lab studies these processes using the developing heart as a model. In the heart, several important transcription factors (TFs) are mutated in human inherited congenital heart disease (CHD), so their study is also important for deciphering the etiology of CHD. Transcription factors must function within the confines of densely packed chromatin, and while the role of chromatin in transcriptional regulation is beginning to be understood, there is a significant chasm between the biochemistry of chromatin remodeling complexes, and their roles in organogenesis. The Bruneau lab lab seeks to integrate mouse models, cell biology, and biochemistry to understand 1. How transcription factors regulate cellular and physiological aspect of heart development, 2. How chromatin remodeling complexes function in vivo to orchestrate cell type-specific gene expression programs and organogenesis. Linking these two major goals is the desire to understand the fundamental basis of lineage-specific gene expression.
Dr. Fineman has an established research program studying the regulation of pulmonary blood flow and pulmonary vascular resistance in the fetal, transitional, and postnatal circulations. In particular, he investigates the role of the vascular endothelium in maintaining pulmonary vascular tone in health and disease states. Utilizing an integrated physiologic, biochemical, molecular, and anatomic approach, he has extensively studied the effects of nitric oxide (an endothelium-derived relaxing factor) and endothelin-1 (ET-1) on the normal circulation of the fetal and newborn lamb, as well as the transitional circulation.
The final trimester of pregnancy and initial months following birth are critical periods for the formation and refinement of connections in the developing human brain. Early brain injury has devastating consequences for brain development, resulting in lifelong disability including cerebral palsy, blindness, epilepsy and learning disability. To understand and ultimately prevent these adverse consequences, the McQuillen lab has developed laboratory models of early brain injury and is using advanced magnetic resonance brain imaging in clinical studies of selected patients at high risk for early brain injury. Using this multi-faceted approach, they take observations from patients to propose and test mechanisms in laboratory models. Mechanisms suggest therapies that once validated form the basis of future clinical trials, the outcome measures of which can be the same tools used to make the initial observation.
Dr. Meadows’ research activities draw upon the use of existing, and the development of novel MRI technologies to address clinical questions facing adults with congenital heart disease. More specifically, current research activities are aimed at developing a computational model to evaluate the pulsatile components of afterload and characterize ventriculo-arterial coupling. The research is driven by the hypotheses are that the pulsatile components of afterload vary with disease, that the resultant imbalance in ventriculo-arterial coupling contributes to heart failure, that interventions may lead to restoration of balance or worsening of the imbalance, and that computational modeling can be used as a tool to predict the course of a particular intervention.
Dr. Moore directs the Congenital Interventional Catheterization Program at UCSF. His current areas of research include the development of intravascular suturing techniques, single ventricle interventional strategies, and interventional MRI. He is the principal investigator on several active clinical protocols, including the Amplatzer Duct Occluder II Clinical Study, the Coarctation of the Aorta Stent Trial (COAST), the Congenital Cardiac Data Registry, the Safety and Efficacy of the Cutting Balloon to Treat Resistant Pullmonary Artery Stenosis, and the Starflex Septal Occludder in Atrial Septal Defect: Long Term Status of Patients Following Closure of ASD (SALSA). He also is co-investigator on several other clinical trials in pediatric cardiology patients.
Dr. Ruppel’s lab studies the role of G-protein coupled receptor signaling pathways in vascular and cardiac development.
Dr. Srivastava’s research interests include understanding the causes of heart disease and using knowledge of cardiac developmental pathways to devise novel therapeutics for human cardiac disorders. Specifically, his laboratory studies the molecular events regulating early and late developmental decisions that instruct progenitor cells to adopt a cardiac cell fate and subsequently fashion a functioning heart. These pathways may be useful in preventing congenital defects and treating acquired heart disease, particularly with cardiac-specific differentiation of embryonic stem cells. Dr. Srivastava is also interested in identifying the causes of human cardiovascular disease by applying modern genetic technologies for the study of complex traits.
Dr. Tabbutt is Associate Professor of Clinical Pediatrics (Cardiology and Critical Care) at UCSF and director of the Pediatric Cardiac Intensive Care Unit. Dr. Tabbutt’s research interests include clinical trials in the PCICU, neurodevelopmental outcomes in patients with congenital heart disease, and post-operative management of staged repair in patients with hypoplastic left heart syndrome.