Stephen Kingsmore, Rady Children’s Institute for Genomic Medicine
Kate Kernan, UPMC
The rapid development of genomic sequencing technologies has decreased the cost of genetic analysis to the extent that it seems plausible that genome-scale sequencing could have widespread availability in pediatric care. Genomic sequencing provides a powerful diagnostic modality for patients who manifest symptoms of monogenic disease and an opportunity to detect health conditions before their development. However, many technical, clinical, ethical, and societal challenges should be addressed before such technology is widely deployed in pediatric practice.
Dr. Kernan’s research is focused on understanding how individual genetic variation contributes to critical illness susceptibility and outcomes in children with severe sepsis. Dr. Kernan’s work has shown that children with pathogenic and likely pathogenic variation in genes known to cause primary immunodeficiencies are at high risk for bacterial infections, evidence of extreme inflammation and requirements for aggressive support therapies. Additional studies of children with innate immune variants, particularly those related to complement disorders, also share unique illness characteristics typical of well described disorders of complement activation such as atypical hemolytic uremic syndrome. Dr. Kernan is an Assistant Professor of Critical Care Medicine at the Children’s Hospital of Pittsburgh of UPMC and a National Institute of Child Health and Human Development Pediatric Critical Care and Trauma Scientist Development Program K12 Scholar. She joined the Department of Critical Care Medicine in 2018 after completing her Pediatric Critical Care Medicine fellowship at UPMC Children’s Hospital of Pittsburgh. She completed residency in Pediatrics at St. Louis Children’s Hospital and graduated with an MD from the University of Pennsylvania, a Master of Fine Arts from New England College, and BA in Biology from the College of the Holy Cross.
Genetic Variation in Primary Immunodeficiency Genes in Children with Severe Pediatric Sepsis
This talk will discuss genetic variation in genes related to primary immunodeficiency and their relationship to severe pediatric sepsis in children admitted to intensive care. My research has shown that children with pathogenic and likely pathogenic variants in genes known to cause primary immunodeficiency have increased odds of bacterial illness, increased inflammation, and increased need for support with extracorporeal membrane oxygenation. In a subset of these children with genetic variation in the innate immune complement pathway, I will demonstrate evidence of genetic and phenotypic relationships to clinical characteristics and organ failure patterns. This represents an opportunity for genetically targeted therapy for critically ill children outside of the neonatal intensive care unit, an example of the possibilities of personalized medicine.
Stephen F. Kingsmore, MD, DSc, is President and CEO of Rady Children's Institute for Genomic Medicine (RCIGM) where he leads a multi-disciplinary team of scientists, physicians, genetic counselors, software engineers and bioinformaticians who are pioneering the use of rapid Whole Genome Sequencing (rWGS®) to enable precise diagnoses for critically ill newborns. In 2021, he led the RCIGM team to set a new record of 13.5 hours for achieving the fastest molecular diagnosis using rWGS, breaking his previous 2018 world record of 19.5 hours. Dr. Kingsmore came to Rady Children’s in 2015 from Children’s Mercy Kansas City, where he was the Director for the Center for Pediatric Genomic Medicine and Executive Director of Medical Panomic, as well as the Dee Lyons/Missouri Endowed Chair in Genomic Medicine at the University of Missouri-Kansas City School of Medicine. He previously served as President and CEO of the National Center for Genome Resources; Chief Operating Officer of Molecular Staging Inc.; Vice President of Research at CuraGen Corporation; Founder of GatorGen; and Assistant Professor at the University of Florida’s School of Medicine. Dr. Kingsmore is board-certified in Internal Medicine and is a Fellow of the Royal College of Pathologists. He received his MB, ChB, BAO and DSc degrees from the Queen’s University Belfast in Ireland. He trained in clinical immunology in Northern Ireland and did his residency in Internal Medicine and fellowship at Duke University Medical Center in North Carolina. In 2012, Dr. Kingsmore was named MedScape Physician of the Year and TIME magazine ranked his first record-breaking time of 50 hours for genome sequencing among the top 10 medical breakthroughs for that year. In 2013, he received the Scripps Genomic Medicine Award and the ILCHUN Prize of the Korean Society for Biochemistry and Molecular Biology.
L7 provides software and services that enable synchronized solutions for science + health. L7’s novel Enterprise Science Platform (L7|ESP) is a scientific process and data management solution that enables life science and healthcare companies to connect people, processes, and systems to accelerate discoveries and drive precision healthcare. Prior to L7 Informatics, Dr. Rangadass was the Chief Strategy Officer at NantHealth following its acquisition of Net.Orange, the company he founded to provide an enterprise-wide platform - Clinical Operating System (cOS) to simplify and optimize care delivery processes in health systems.
Lawrence (Lance) Prince, MD, PhD, is the Division Chief for Neonatal and Developmental Medicine at Stanford. Dr. Prince’s research interests include the molecular and cellular mechanisms controlling lung development and the maturation of the fetal and neonatal immune systems. He has a particular clinical interest in managing and treating neonatal lung diseases, especially bronchopulmonary dysplasia (BPD) in babies born extremely preterm. Dr. Prince’s research team focuses primarily on the development of innate immunity during fetal life as it impacts health and disease in preterm infants. The laboratory is investigating how microbes including Group B streptococcus exploit the unique features of neonatal macrophages to avoid immune detection and cause disease, as well as leading a number of clinical and translational investigations.
Neonatal Molecular Precision Medicine and Disease Resilience
While the complications of extreme prematurity can be devastating, many patient have excellent outcomes. In studying the molecular basis for the chronic lung disease bronchopulmonary dysplasia, we identified programs of gene expression correlating with disease protection or resilience. We hope that future genomic studies will help identify therapies that will help achieve normal human development.
Dr. Martin Reese is Co-Founder, CEO, and President at Fabric Genomics (formerly Omicia). He is a pioneer in the field of genomics and bioinformatics, and has led and co-founded various companies such as ValiGen and Neomorphic. He co-created the two machine-learning algorithms VAAST and Phevor, which are key components of Fabric Genomics’ software platform and an essential part of the bioinformatics pipelines at institutions such as Rady Children’s Institute for Genomics, Genomics England, and LabCorp. Dr. Reese speaks all over the world about algorithms for genomics, machine-learning, AI, deep phenotyping, genomic medicine, and precision medicine. He holds a Master’s Degree in Medical Informatics from the University of Heidelberg and a Ph.D. in Genetics, jointly from the University of Hohenheim and The University of California, Berkeley.
Dr. Hegde is the SVP and Chief Scientific Officer, Global Laboratory Services, PerkinElmer and Adjunct Professor at Georgia Institute of Technology. Previously, she was the Executive Director of Emory Genetics Laboratory and Professor of Genetics and Pediatrics at Emory University. The focus of her work is the development and implementation of high-throughput omics based strategies for discovery and clinical testing. She has over 25 years’ experience in clinical diagnostics, which includes laboratory administration, regulation, management, reimbursement, and interpretation of genomic variation. She serves on scientific boards and has been invited to present her work globally. Currently, she is on the board of American Board of Genetics and Genomics Foundation (ACMGF). She received a B.Sc. and a M.Sc. from the University of Bombay, India, and a Ph.D. from the University of Auckland, New Zealand. She completed post-doctoral studies at Baylor College of Medicine and is board certified in Clinical Molecular Genetics.
Omics Based Technologies in Neonatal Care
Newborn screening is public health program which has had significant impact early detection of rare diseases. Since its implementation significant technological advances have led us to genome sequencing and use of omics based technologies. This date driven presentation will demonstrate the utility of these tools in neonatal and pediatric care
Paul Kruszka is a board-certified clinical geneticist who uses genomic and precision medicine to enhance the delivery of health care to individuals with rare diseases. Prior to working at GeneDx, Dr. Kruszka spent a decade at the National Institutes of Health conducting genomic research and taking care of individuals with rare genetic diseases. Dr. Kruszka is credited with the clinical and molecular delineation of multiple novel genetic conditions. Dr. Kruszka attended medical school at the University of Michigan and completed a family medicine residency at the University of Virginia and a clinical genetics residency at the National Human Genome Research Institute at the National Institutes of Health.
High Throughput Neonatal Sequencing: The New Standard of Care
Until recently, neonatal sequencing investigations have been limited to small academic studies. In this report we review over 1500 cases of rapid exomes and genomes in critically ill infants. This data, which includes diagnostic rates and clinical indications lay the groundwork for future sequencing guidelines and standard of care.