Cardiovascular Research

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Director: Vaughn A. Starnes, MD

Emerging Initiative

More than 200 children in the United States are waiting for a heart transplant to live.  Many of these children may die waiting for a donated organ. 

Scientists at our hospital are exploring the use of xenografts, hearts from animals such as pigs to help sustain patients until human organs are available.  But using xenografts requires genetic modification to avoid the patient rejecting the heart.  Through research, rejection time has been extended to as long as six months (as compared to a few hours). 

Researchers are now asking:  "Can this period be stretched further?"

Mary Kearns-Jonker, PhD is tackling this question in two ways:

• conducting research to understand the immune response that is responsible for xenograft rejection
• examining techniques that induce tolerance to xenografts

In an ongoing mouse-model study, she has introduced into the bone marrow a gene that encourages its immune system to accept xenograft cells. The results are promising: mice receiving genetically modified bone marrow permanently accept heart grafts. If techniques like these can be successfully applied in humans, then xenografts might serve as more than temporary solutions to organ need—they may become semipermanent transplants, sustaining the lives of children for many years. 

Research Focus

The program is a joint partnership between the Research Institute and the Heart Institute led by Dr. Vaughn Starnes, who contributes significantly to its vision and financial support.  The goal of the Cardiovascular Research Program is to support and advance the pediatric and adult cardiac and vascular programs through basic and applied research activities. The basic science research activities take place in the laboratories on the 4th floor of The Saban Research Institute, and the clinical research is carried out at Childrens Hospital Los Angeles and in the laboratories at the USC Health Science Campus (HSC).

At the Saban Research Institute of Childrens Hospital Los Angeles, Cardiovascular research is carried out by independent principal investigators: 

• Dr. Starnes
• Dr. Kearns-Jonker

The three areas studied include:

1. Heart Valve Biomechanics and Tissue Engineering
2. Molecular Aspects of Organ Graft Rejection
3. Mechanisms of Graft Fibrosis

The immediate goals of the Program are to establish the world-class presence of heart valve research in The Saban Research Institute, and to expand research in tissue engineering and computational modeling, and to identify new synergies within the group for continuing our pioneering work in basic and applied cardiovascular research.

Accomplishments

Xenotransplantation
Principal Investigator:  Dr. Mary Kearns-Jonker
Organs derived from pigs (xenografts) represent a solution to the severe organ shortage that currently plagues human organ transplantation. The Xenotransplantation Laboratory led by Dr. Kearns-Jonker is studying the immunology of xenograft rejection and the application of gene therapy to induce transplantation tolerance.  Ongoing research projects include (i) analysis of immunoglobulin genes used by organ recipients to target transplanted xenografts, (ii) analysis of the molecular structure of xenoantibody-antigen binding, making use of site-directed mutagenesis and computer  modeling, (iii) development of treatment strategies to prevent graft rejection, including the application of anti-idiotypic antibodies and small molecular inhibitors designed to specifically target the xenoantibody binding site, and (iv) the application of gene therapy to induce transplant tolerance.  Success in any of these research projects will offer greater quality of life to organ transplant recipients, as they will reduce the severe side-effects associated with currently available immunosuppression therapies.  The xenotransplantation laboratory recently reported the successful application of gene therapy using lentiviral vectors to induce chimerism and long"term heart graft survival in a mouse model. The long-term goals of this work are to apply gene therapy to induce transplantation tolerance.

Clinical Research
Principal Investigator:  Dr. Vaughn Starnes
Clinical Research is performed within The Heart Institute and directed primarily by Drs. Vaughn Starnes, the Chair of Cardiothoracic Surgery at Childrens Hospital Los Angeles and at USC, and by his Dept. members Drs. Mark Barr, and Winfield Wells.  Dr. Starnes is involved in a number of clinical trials, such as barrier films to prevent adhesions during open-heart surgery (with Dr. Wells) and the use of Viagra to treat pulmonary hypertension (with colleagues in Cardiology).  Dr. Barr is to advance organ preservation technologies and to develop new strategies for the treatment and prevention of chronic rejection in heart and lung transplant patients.

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