Where do generalists fit in the exploding field of genetics? Until recently genetics has played a relatively small part in the medical school curriculum. Its research has proceeded at a phenomenal rate along with its implications for enhanced patient care. Generalists’ expanding responsibilities to incorporate this thread of genetics through each patient encounter and acknowledge the role of genetics in every disease has become increasingly apparent. However the emerging gap in physician knowledge has created an enormous need for education in a previously underemphasized area of medical education.

As generalists, we are the gateway (not gatekeepers) to better health. This session is designed to help us understand the emerging importance of viewing each patient through a "genetic lens." Basic genetic concepts, core competencies and new paradigms will be discussed using a collaborative faculty presentation.

Strategies for teaching genetics and incorporating its practice into primary care will include "missed opportunities," case presentations and interactive educational games. Examples of resources, including internet user-friendly sites will be distributed.

Speakers:

The pipeline of new therapies flowing from the bench to the bedside is extremely long and tortuous, with many "valves" that must be opened. Expertise is required in both basic and clinical research to conduct Investigational New Drug-directed early phase human clinical trials or to become skilled in the design and implementation of pre-clinical studies necessary to effectively progress basic observations into human trials. For the academician, the challenges can be legion. This session will begin with an example of the infrastructure required for an academic center to foster translational research. The symposium will then cover three of the major aspects of new drug development. First, we will explore the preclinical selection of appropriate targets and the models in which to test them. Second, we will explore the pharmaceutical pipeline to give participants knowledge of new clinical agents. Third, we will learn about coordinating the early stage clinical trials with regulatory agencies. We will close with an academician¹s perspective of the end of the pipeline based on recent gene therapy trials for hemophilia.

Introduction to Translational Research: Opening the Valves of the Pharmaceutical Pipeline
Timothy Cripe, Cincinnati Children's Hospital Medical Center, Cincinnati, OH

Pediatric Malignancies Provide Unique Cancer Therapy Targets
Jeffrey Toretsky, Lombardi Comprehensive Cancer Center, Washington, DC

Exploiting Genetic Defects for Targeting Oncolytic Viruses to Pediatric Cancers
Timothy Cripe, Cincinnati Children's Hospital Medical Center, Cincinnati, OH

A Comparative and Preclinical Approach Toward Drug Development
Chand Khanna, National Cancer Institute, National Institutes of Health, Bethesda, MD

Developing Drugs in the Era of Targeted Therapy
Pamela S. Cohen, Novartis Pharmaceuticals Corporation, Florham, NJ

Ask Not What CTEP Can Do for You…Moving Agents Through the Pipeline
Barry Anderson, National Cancer Institute, National Institutes of Health, Rockville, MD

Special Delivery: Novel Approaches and Challenges to Gene Delivery
Mark Kay, Stanford University Medical Center, Stanford, CA

Traditional newborn screening has successfully identified and allowed treatment for newborn infants with several inborn errors of metabolism including phenylketonuria, galactosemia and biotinidase deficiency since its advent in the 1960s. Novel methodologies have been developed that allow detection of a large group (>30) of inherited metabolic disorders that have not been screened for by traditional methodologies. Expanded screening has now been introduced in several states and will likely continue to be developed throughout the United States.

This workshop will review traditional approaches to newborn screening and summarize novel methodologies including tandem mass spectroscopy. The experience in public health programs will be described, and the outcome of several years of expanded newborn screening (tandem mass spectroscopy) will be summarized. Prospects for future screening methodologies will be reviewed. This workshop will bring the pediatrician rapidly up to speed on expanded newborn screening and describe the clinical benefits for patients who are identified at an early age.

Expanded Newborn Screening: The North Carolina Experience
Joseph Muenzer, University of North Carolina, Chapel Hill, NC

Newborn Screening and Public Health: Past, Present and Future Perspectives
Ken Pass, Wadsworth Center, NYS Department of Health, Albany, NY

Development of Novel Methodologies for Newborn Screening
David S. Millington, Duke University Medical Center, Research Triangle Park, NC
 

Understanding the function of genes and other parts of the genome is known as functional genomics. The Human Genome Project is just the first step in understanding humans at the molecular level. Now that the sequencing phase of the human and mouse genomes is complete, many questions remain unanswered, including the function and regulation of most of the estimated 30,000–35,000 mouse and human genes. The mouse has a long and rich history in biological research and many consider it a model organism for the study of human development and disease. Over the past few years, exciting progress has been made in developing techniques for chromosome engineering, mutagenesis, mapping and maintenance of mutations and identification of mutant genes in the mouse. Additionally, whole genome sequence analysis of many different species is proving to be incredibly fruitful in identifying critical gene regulatory motifs. In this workshop, we will present a few of the techniques that are being applied to the daunting yet exciting task of functional genomic analysis in the mouse.
 

This mini course will set the stage for several discussions of particular issues of major importance and interest. What is "preparedness" and what are the real risks of continuing terrorism in the United States? What is the current status of preparedness in the U.S. hospital and public health systems? How do children differ from adults in terms of response to weapons of mass destruction (chemical, biological and radiological)? How do these differences matter in disaster planning? Are the needs of children being incorporated in local, state and federal disaster plans? Smallpox, anthrax and other biological threats: Where do we stand? What do we do? Nuclear power plants, nuclear weapons, dirty bombs and potassium iodide: What do we know? The mental health consequences of terrorism: What have we learned since 9/11, how do we prepare children for an increasingly vulnerable world, building resiliency and sustaining a positive vision. The new pediatric agenda: What do we have to teach students, residents and pediatricians about the pediatric aspects of terrorism planning. Children and exposure to weapons of mass destruction: science and the essential research agenda.

Introduction
Paul H. Saenger, Albert Einstein College of Medicine, Montefiore Medical Center, Bronx, NY

Welcome and Context
Irwin Redlener, National Center for Disaster Preparedness, Columbia University Mailman School of Public Health, New York, NY

Pediatric Preparedness for Terrorism and Disasters
David S. Markenson, Columbia University Mailman School of Public Health, New York, NY

Biological Weapons of Terror: What Pediatricians Need to Know
Theodore J. Cieslak, U.S. Army Research Institute of Infectious Diseases, Ft. Detrick, MD

Helping Children and Families Cope with Terrorism
David J. Schonfeld, Yale University School of Medicine, New Haven, CT

Radiologic Terrorism, Children and the Question of Potassium Iodide
Thomas P. Foley, University of Pittsburgh, Children's Hospital of Pittsburgh, Pittsburgh, PA

Anorexia nervosa is an eating disorder characterized by a relentless and obsessive pursuit of thinness that most commonly develops in adolescent females. The severe restriction of calories and compulsive exercising that can occur in this chronic condition may result in life-threatening weight loss. In addition to the serious medical complications associated with semi-starvation and severe energy deficits, there are often significant psychological and social problems that may precede or follow, as well as complicate the treatment during, the active phase of the illness. Practitioners and researchers in pediatrics and adolescent medicine in the field of eating disorders have generally focused on the acute and the chronic medical complications associated with anorexia nervosa. Although no organ is spared the effects of chronic malnutrition that occur with this condition, two that have the potential of long-term biological morbidity are the skeletal and reproductive systems. The long-term clinical outcomes of continued morbidity in these organs are osteoporosis and amenorrhea with reproductive failure, respectively. The latest research findings and their clinical implications relative to these organ systems will be discussed, and future research directions will be explored. In addition to the biological effects of anorexia nervosa, we shall address the biological vulnerability to developing anorexia nervosa, based on genetic predisposition. Emerging data from research studies and their clinical implications will be presented.

Overview
Richard E. Kreipe, University of Rochester School of Medicine, Golisano Children's Hospital at Strong, Rochester, NY

Morbidity of the Skeletal System in Anorexia Nervosa
Neville H. Golden, Schneider Children's Hospital, New Hyde Park, NY

Morbidity of the Reproductive System in Anorexia Nervosa
S. Jean Emans, Harvard Medical School, Children's Hospital Boston, Boston, MA

Genetic Susceptibility to Anorexia Nervosa
Wade Berrettini, University of Pennsylvania, Institute of Neurological Sciences, Center for Neurobiology and Behavior, Philadelphia, PA

Discussion
 

Congenital heart defects are present in nearly 1% of all newborns and continue to be a significant cause of death in infancy. A major goal for clinicians and basic scientists has been to understand the sources of these relatively common developmental errors. With the completion of the sequencing of the human genome, molecular genetic efforts directed at finding genes for monogenetic traits have accelerated dramatically. This topic symposium is directed toward exploring the state of the art understanding of the molecular basis of certain syndromic forms of congenital heart defects as well as their implications for non-syndromic heart disease. The discussion will focus on four syndromes (Holt-Oram, heterotaxy, DiGeorge/velocardiofacial, and Noonan syndromes) for which disease genes have been discovered and insights into disease pathogenesis are available.

Overview
D. Woodrow Benson, Children's Hospital Medical Center, Cincinnati, OH

Holt-Oram Syndrome and TBX5
Craig Basson, Cornell University Medical College, New York, NY

Molecular Basis of Heterotaxy Syndromes
Martina Brueckner, Yale University School of Medicine, New Haven, CT

DiGeorge/Velocardiofacial Syndromes and 22q11
Elizabeth Goldmuntz, Children's Hospital of Philadelphia, University of Pennsylvania, Philadelphia, PA

Noonan and Related Syndromes and PTPN11
Bruce D. Gelb, Mt. Sinai School of Medicine, New York, NY

Discussion
 

Children who are victims of violent behavior or merely observers of violence may learn destructive or self-destructive patterns of behavior. Violence is a major public health problem. This symposium will focus on breaking the cycle of violence and will showcase speakers who are working on violence prevention in the pediatric emergency department, school and community. The speakers will demonstrate what can be done by physicians who see the importance of this issue and the ways in which we can make a difference.

Violence Prevention in Primary Care: Moving from Public Health to Private Practice
Robert D. Sege, Tufts-New England Medical Center, Boston, MA

Beyond Treat and Street: Violence Prevention in the Emergency Department
Joel Fein, The Children’s Hospital of Philadelphia, PA

Efforts in the Community
Sheryl A. Ryan, University of Rochester School of Medicine, Rochester, NY

The National Children’s Study is a national prospective, longitudinal study of environmental effects, including physical, chemical, biological and psychosocial effects, on child health and development. The goal of the study is to improve the health and well-being of children. The study will examine these environmental effects on the health and development of more than 100,000 children across the United States, following them from before birth until age 21. The study is led by a consortium of federal agency partners: the U.S. Department of Health and Human Services, including the National Institute of Child Health and Human Development (NICHD); the National Institute of Environmental Health Sciences (NIEHS); the Centers for Disease Control and Prevention (CDC); and the U.S. Environmental Protection Agency (EPA). For additional information, visit the website at http://www.nationalchildrensstudy.gov/.

The National Children’s Study—An Overview
Duane Alexander, NICHD, National Institutes of Health, Bethesda, MD

The National Children’s Study—Methods
Peter C. Scheidt, National Institutes of Health, Bethesda, MD

Children’s Health and Environmental Exposures: The Most Important Unanswered but Answerable Questions
Michael Weitzman, The AAP Center for Child Health Research at the University of Rochester, Rochester, NY

The neuroendocrine and genetic control of puberty remains one of the fundamental mysteries in human biology. Recent advances derived from sequencing the human genome have enabled the identification of novel genes affecting human puberty via clinical investigations of single patients or families with human disorders that were simply not possible even three years ago. Using these techniques, clinical investigators have been able to identify and chart several genetic defects affecting reproductive development and translate these insights into an improved understanding of how the brain controls puberty in the human. The lecture will focus upon several of these major advances and describe a new gene recently discovered that controls puberty.

William F. Crowley, Harvard Medical School, Massachusetts General Hospital, Boston, MA

The application of imaging technologies to solving questions in biology and medicine is revolutionizing medicine by accelerating analyses in situ and in vivo and providing new perspectives on biological processes as diverse as development, neoplasia and injury repair. In this plenary session, three internationally recognized speakers will focus on developmental processes and discuss how these new imaging technologies are providing dynamic insights into the genetic and epigenetic mechanisms that underpin hematopoiesis and vascular development.

Introduction
Lisa M. Guay-Woodford, University of Alabama at Birmingham, Birmingham, AL

Dynamic Imaging of Fluid Forces in Developing Mouse Vasculature
Mary Dickinson, Beckman Institute–Caltech, Pasadena, CA

Microscopic Imaging of Angiogenesis
Donald M. McDonald, University of California, San Francisco, CA

Watching Hematopoietic Stem Cell Engraftment and Hematopoiesis in Living Animals
Christopher H. Contag, Stanford University School of Medicine, Stanford, CA

Questions from the audience
 

This program will focus on emerging trends in hematopoietic stem cell transplantation for children with primary immunodeficiencies. Topics to be covered will include the use of alternative donor sources such as unrelated cord blood, new approaches with lower intensity pre-transplant conditioning regimens and an update on transplant outcomes for some of the more common primary immunodeficiencies such as SCID, WAS and HLH.

Hematopoietic Stem Cell Transplant for Primary Immunodeficiency Disorders: Update of Outcomes and Unrelated Cord Blood
Alexandra H. Filipovich, Children's Hospital Medical Center, Cincinnati, OH

Nonmyeloablative Stem Cell Transplant for Congenital Immunodeficiencies
Kanchana Rao, Great Ormand Street Hospital for Children, London, United Kingdom

Hematopoietic Stem Cell Transplant for Hemophagocytic Lymphohistiocytosis: Results from the Multi-institutional National Marrow Donor Program HLH Protocol
K. Scott Baker, University of Minnesota, Minneapolis, MN

In 1991 recombinant human glucocerebrosidase was approved by the FDA and introduced into clinical practice for the treatment of type 1 Gaucher disease. Since then over 3,000 children and adults with this disease have received this enzyme replacement therapy (ERT) and have experienced arrest of the progression of their disease and reversal of many of the signs and symptoms of Gaucher disease.

The success of this experience has encouraged the development of other ERT products for the treatment of lysosomal storage diseases and treatments for Fabry disease and Mucopolysaccharidosis 1were FDA approved in April 2003. In this topic symposium we will review the effects of ERT for these three disorders: Gaucher disease, Fabry disease and Mucopolysaccharidosis 1. In addition, we will review progress in the development of ERTs for other lysosomal storage disorders.

Gaucher Disease: 10 Years Experience with Enzyme Replacement Therapy
Joel Charrow, Feinberg School of Medicine, Northwestern University, Chicago, IL

Enzyme Replacement Therapy for Fabry Disease
Christine Eng, Baylor College of Medicine, Houston, TX

Treatment of MPS I with Enzyme Replacement Therapy
Joseph Muenzer, University of North Carolina, Chapel Hill, NC

This session will provide insight into the epigenetic mechanisms responsible for gene expression and its impact during development resulting in programming. These mechanisms may underlie interactions between different nutritional and environmental influences on gene expression. Various examples will be discussed, and the life-long impact of these processes on the phenotype described. This session will provide insight into the relationship between fetal/neonatal events and long-term effects that manifest as chronic adulthood diseases. The speakers will present various aspects of this phenomenon and its physiological outcome.

Evolution of Imprinted Disease Susceptibility Genes
Randy L. Jirtle, Duke University Medical Center, Durham, NC

The Contribution of Genomic Imprinting and Epigenetics to Phenotype
Arthur L. Beaudet, Baylor College of Medicine, Houston, TX

Maternal Care, DNA Methylation and the Development of Individual Differences in Stress Reactivity
Michael Meaney, McGill University, Montreal, Canada
 

Vaccines have an important function in preventing birth defects. The most obvious one is rubella vaccine and its application for the purpose of preventing congenital rubella syndrome (CRS) will be discussed. In addition, prospects of the development of other relevant vaccines will be presented. These will include: cytomegalovirus, parvovirus, herpes simplex and malaria. The first three, because they affect the fetus directly; the last, because of its adverse effect on pregnancy that results in small-for-gestational-age newborns.

Elimination of Rubella from the Americas by the Year 2010
Mirta Roses Periago, Director of PAHO, Panamerican Health Organization (PAHO), Washington, DC

Prevention of CRS by Universal Application of the Rubella Vaccine
Susan E. Reef, Center for Disease Control, Atlanta, GA

Prospects for a Vaccine Against Cytomegalovirus
Stanley A. Plotkin, Aventis Pasteur and the University of Pennsylvania, Doylestown, PA

Prospects for a Vaccine Against Herpes Simplex
Richard J. Whitley, University of Alabama at Birmingham, Children's Hospital, Birmingham, AL

Prospects for a Vaccine Against Parvovirus B-19
Neal S. Young, National Institutes of Health, Bethesda, MD

Prospects for a Vaccine Against Malaria
N. Regina Rabinovich, Bill & Melinda Gates Foundation, Seattle, WA

Discussion

Genetic studies in humans have expanded our understanding of pediatric sudden death. This session will explore the genetic mechanism, pathophysiology and potential treatments of three genetic causes of sudden death in children.

Introduction
James Bristow, University of California, San Francisco, CA

Fatty Acid Oxidation Disorders and Sudden Death
Arnold W. Strauss, Vanderbilt Children's Hospital, Nashville, TN

Cardiac Channelopathies and Pediatric Sudden Death
Jeffrey A. Towbin, Baylor College of Medicine, Houston, TX

Familial Hypertrophic Cardiomyopathy and Sudden Death
Christine Seidman, Howard Hughes Medical Institute, Brigham and Women's Hospital, Boston, MA
 

Worldwide, more than 1,500 children per day become infected with HIV through mother-to-child transmission. Currently there are 2.7 million children living with HIV infection across the globe, >90% of whom reside in developing countries. While there have been enormous successes in the prevention and treatment of pediatric AIDS in the United States and Europe, it remains an open question as to how effectively these public health gains can be replicated in the poor countries of the world, which bear the greatest burden of disease. Efforts to develop an HIV vaccine appropriate for preventing infection among the world's children and adolescents are finally under way on a global scale. We will discuss these issues and accompanying controversies as they apply to the children of the developing world.

AIDS in Children—A Global Public Health Crisis
David L. Pugatch, Hasbro Children's Hospital and Brown Medical School, Providence, RI

Preventing Mother-to-Child Transmission of HIV in Developing Countries—Successes, Failures and Challenges
Catherine M. Wilfert, Elizabeth Glaser Pediatric AIDS Foundation, Santa Monica, CA and Washington, DC

HIV Treatment for Children—Can the Successes of Rich Countries Be Duplicated in Resource-Poor Settings?
Mark W. Kline, Baylor College of Medicine, Houston, TX

Finding an AIDS Vaccine That Works for the World's Children
Richard A. Koup, Vaccine Research Center, National Institutes of Health, Bethesda, MD

In 1929, a visionary band of 25 pediatric physician-scientists, spurred by their passion for science and their commitment to children, founded the Society for Pediatric Research. In the intervening 75 years, pediatric investigators have wrought a breathtaking suite of therapeutic breakthroughs—from the care of premature neonates, to effective immunoprotection from childhood disease, to novel therapeutic strategies for childhood leukemia. More recently, the completion of the Human Genome Project has identified new opportunities to delineate the impact of genetic variation on childhood disease expression.

Four leaders in Pediatric Research will celebrate the accomplishments of the past 75 years and share their perspectives about the challenges that lay before us.

Introduction
Gail J. Demmler, President, Society for Pediatric Research

The Problem of Prematurity: The Impact of Surfactant and the Challenge of Long-Term Morbidity
Samuel Hawgood, University of California Medical Center, San Francisco, CA

The Problem of Childhood Infectious Diseases: The Impact of Vaccine Development and the Challenge of Emerging Infections
Margaret K. Hostetter, Yale University School of Medicine, New Haven, CT

The Problem of Childhood Leukemia: The Impact of Combination Chemotherapy and the Challenge of Neuro-cognitive Morbidity
Alan L. Schwartz, Washington University Medical Center, St. Louis, MO

The Problem of Genetic Disease: The Impact of the Human Genome Project and the Challenge of Translation to Innovative Therapy
Edward R. B. McCabe, David Geffen School of Medicine at UCLA, Los Angeles, CA

Sequencing of the human genome has led to extraordinary acceleration in the pace of genomics research. The large sequencing capacity developed during sequencing of the human genome is now being applied to other genomes and re-sequencing of humans. This session will explore the remarkable utility of sequence comparison for understanding gene regulation and function as well as new understanding of the basis of common human diseases.

Multiple Genome Sequence Comparisons To Understand Gene Regulation
Eddy Rubin, Lawrence Berkeley National Laboratory, Berkeley, CA

Human Sequence Variation and Disease Gene Identification
David R. Cox, Perlegen Sciences, Mountain View, CA

Large-Scale Resequencing of Candidate Genes in Congenital Heart Disease
Deepak Srivastava, The University of Texas Southwestern Medical Center, Dallas, TX

The potential applications for using regenerated cells and tissues to treat injury and disease are unlimited. Early stem research concentrated on the hematopoietic stem cells of the bone marrow, but stem cells are now known to exist in most organs of the body. Furthermore, it may be possible to return mature, differentiated cells to a undifferentiated, stem-like state. This symposium will first provide an overview of non-hematopoietic stem cells, then focus on two rapidly-progressing areas of research—those of regenerating nervous tissue and liver.

Neural Stem Cells: Developmental Insights May Suggest Therapeutic Options
Evan Y. Snyder

Hepatic Stem Cells and the Potential of Liver Repopulation for Cell Therapy
Sanjeev Gupta, Albert Einstein College of Medicine, Bronx, NY