Mission: To Leverage Scientific Innovation and Discovery to Cure Children’s Heart Disease

Since the modern genesis of care for congenital heart disease in the 1940s, the driving force for advances in the field has been the development of increasingly complex and sophisticated operations and interventional procedures and applying these procedures to younger and smaller patients. This approach has had a profoundly positive effect on survival and quality of life over the decades. However, it has been directed at repairing but not curing congenital heart disease, and so increasing numbers of our young patients, particularly those who require multiple surgeries, develop heart rhythm abnormalities and heart failure as they enter adult life. The Basic Science and Engineering Initiative of the Children’s Heart Center is a timely partnership with Stanford University’s Basic Science and Engineering Departments, to transform the care of children with heart disease by building a community of researchers across many areas of basic science and engineering dedicated to this problem. Our team currently includes faculty in the Departments of Genetics, Bioengineering, and Pediatrics who are pursuing interdisciplinary approaches to better understand and ultimately modulate heart development.

MOONSHOT GOALS: We aim to lay the foundations in basic science and engineering to build toward long-term solutions to curing children’s heart diseases. Some of these solutions include:

-       Building therapeutic heart tissues from stem cells. Our team’s advances in personalized stem cell biology and complex tissue engineering capabilities, including large-scale construction, multicellular composition, vascularization (i.e. blood flow), and ability to grow with host tissue, will enable the generation and replacement of functional heart valves, heart tissue and even a whole heart at any scale of development.

-       Determine the genetic cause of any individual patient’s congenital heart defect. Heart defects are often caused by defects, or variation, in our DNA. Our team is using innovative experimental genomic technologies and novel computational algorithms to study genetic variation in all cell types in the heart during all stages of development, so that we can determine how particular variants lead to each congenital heart defect.

-       Find methods to modulate heart development in utero. Once we can understand how patient-specific congenital heart disease arises, we can leverage our team’s expertise in advanced genomic screens, stem cell engineering, and surgical bioprinting to develop case-by-case therapies to correct or reverse congenital heart disease even as the fetus develops.

BASIC SCIENCE AND ENGINEERING PROGRAM STRUCTURE: The Director of the BASE initiative is Dr.  Marlene Rabinovitch, Dwight and Vera Dunlevie Professor of Pediatrics (Cardiology), an experienced and internationally renowned physician scientist and vascular biologist with broad knowledge of the clinical and scientific arenas. Our first three BASE scientists include: Dr. Jesse Engreitz, Assistant Professor of Genetics, who studies how variants in noncoding regions of the genome relate to protein coding regions of the genome in each of the multiple cell types in the heart; Dr. Mark Skylar-Scott, Assistant Professor of Bioengineering, who is building heart tissue, valves, and blood vessels using sophisticated bioprinting and bioreactor technologies with human cells and biological substrates; and Dr. Casey Gifford, Assistant Professor of Pediatrics and Genetics (by courtesy), who is investigating patterns of oligogenic inheritance and mapping genetic variants as they relate to different processes in cardiac development. Our partnership with the Basic Science and Engineering Departments at Stanford assures an academic infrastructure to support the career development of our scientists through the dynamic interface with graduate students, training programs, and access to the latest developments in their fields.

We now plan to complement the expertise of the current BASE group with scientists who are innovators in data science, imaging, metabolism, and cell physiology. Their insights will provide the new tools and the knowledge to use them in determining when, where, and how to intervene to normalize heart development and function as early as fetal life.

Our BASE scientists are housed in the state-of-the-art Biomedical Innovations Building on the main School of Medicine Campus within easy walking distance of the Basic Science and Engineering Departments as well as the new hospital and clinical programs. This proximity was specifically built into the program design to promote communication, familiarity, collaboration, and synergy between the basic scientists, engineers, and clinicians. Moreover, our team is able to leverage the rich and highly innovative environment that Stanford provides through existing programs such as BioDesign and BioX, as well as new programs such as the Chan-Zuckerberg Biohub, and the interdisciplinary Chemistry, Engineering, and Medicine for Human Health (ChEM-H) program. There is also the outstanding Silicon Valley environment that encourages and facilitates translation of fundamental discovery to the clinic.

PROGRAM SUPPORT AND COMMITMENT: Dr. Frank Hanley, Executive Director of the Betty Irene Moore Children’s Heart Center, together with Dr. Stephen Roth, Co-Director, have worked closely with the greater Stanford community to obtain the resources, support, and commitments necessary to develop a successful Basic Science and Engineering Program. The leadership of Lucile Packard Children’s Hospital and the Lucile Packard Foundation for Children’s Health (the hospital’s dedicated entity for philanthropic giving and program development) committed to raising $110M to support the BASE Program, of which almost one half has already been secured for the program. The Dean of the School of Medicine, Lloyd Minor, MD, has already committed wet and computational laboratory space, in addition to space for administrators and core facilities, in the newly constructed state-of-the-art Biomedical Innovations Building.

OUR AFFILIATED CLINICAL PROGRAM: The Betty Irene Moore Children’s Heart Center, founded in 2007 under the leadership of Dr. Frank Hanley, Head of Pediatric Cardiac Surgery, has assumed national leadership in the volume and complexity of patients with congenital heart disease treated at the hospital, in providing outstanding and innovative clinical care in a collaborative environment, and in contributing to the advancement of the field through clinical and translational research.  The faculty includes 45 pediatric and adult congenital cardiologists and 22 pediatric cardiac surgeons, anesthesiologists, and radiologists, caring for neonates to adults with the entire spectrum of heart disease. Furthermore, through the Clinical Outcomes and Translational Research Program directed by Doff McElhinney, MD, the Children’s Heart Center offers resources to promote clinically-based research by providing a core of biostatisticians, data managers, and support staff for faculty and postdoctoral fellows. Drs. Doff McElhinney, MD, and Sushma Reddy, MD, whose research focuses on understanding and developing biomarkers for incipient heart failure in children, serve as Clinical Liaisons between the clinical programs in the Children’s Heart Center and the BASE Program. The following are the major clinical programs: 

-       The Single Ventricle Program, under the direction of Sharon Chen, MD, focuses on improving the short- and long-term management of patients with single ventricle physiology, from fetal life to adulthood, and investigates the effects of this physiology on other critical organ systems.

-       The Pulmonary Artery Reconstruction Program, under the direction of Doff McElhinney, MD, investigates the management of patients with structural, congenital, and acquired pulmonary artery abnormalities, and the effects of these abnormalities on heart function.

-       The Cardiovascular Connective Tissue Disorders Program, under the direction of Tom Collins, MD, is focused on improving the management of monogenic disorders that affect connective tissue formation and lead to major abnormalities in the aorta, coronary, and pulmonary arteries.  

-       The Heart Failure and Transplant Program, under the direction of David Rosenthal, MD, focuses on advances in the management of pediatric patients with heart failure, including medical therapy, ventricular assist devices, and transplantation.

-       The Electrophysiology Program, under the direction of Anne Dubin, MD, manages patients with heart rhythm disturbances and has been a leader in developing interventions and pacemaker strategies for children with heart failure.

-       The Pulmonary Vascular Disease Program, under the direction of Jeffrey Feinstein, MD, is one of the leading centers worldwide for improving the diagnosis and treatment of children with pulmonary hypertension and other pulmonary vascular diseases.