Major Research Domains

Research Affiliates

Core Services
  Behavioral
  Science Core

  Genetics Core

  Infant Primate
  Research
  Laboratory

  Instrument
  Development
  Laboratory

  Neuroscience Core

Research Emphasis Area on Infectious Disease and Immunology

Coordinator: Craig Rubens, M.D., Ph.D.

The Research Emphasis Area on Infectious Disease and Immunology focuses on congenital and perinatal infections that have profound effects on pregnancy outcome. Congenital and perinatal infections are associated with birth defects and poor developmental outcomes in infants. Several microbial pathogens cause in utero infections, which are associated with significant congenital defects, prematurity, postpartum sequelae, and /or stillbirth delivery. Likewise, perinatal infections are associated with severe neonatal morbidity and mortality, and may result in significant neurologic sequelae--such as clinical blindness, seizures, spasticity disorders, and developmental and learning disabilities.

This REA is designed to focus on both the basic biological understanding of the pathogenesis of these infections, their relationship to the development of the immune response and its inability to prevent these infections in utero or immediately postpartum, their role in preterm labor, preterm birth, and fetal loss, and on the improvements in the clinical approach to prevention and/or treatment of these infections.

The first focus is on understanding the pathogenesis of congenital viral infections-including cytomegalovirus (CMV), human immunodeficiency virus (HIV), and herpes virus infections (HSV). These include understanding the basic molecular mechanisms these viruses use to infect the human host and evade immune defenses. In addition, studies are addressing identification of patients at risk for developing poor fetal outcomes. Techniques involve include basic cellular, molecular biology and epidemiological analysis.
The second focus involves understanding the development of the immune response during and after pregnancy. Understanding the molecular mechanisms involved in both the cellular and humoral responses are critical for understanding the failure of the pregnancy milieu to prevent and/or contain infections that lead to a devastating outcome. Techniques involved in studying the immune response include state-of-the-art microscopy, molecular and cell biology, and genomic and proteomic analysis. Significant successes have been achieved through utilizing these technologies to enhance our understanding of the ontogeny of the cellular immune response, providing valuable insights into the development of the immune system in the fetus and neonate.
The third focus is on the pathogenesis of bacterial perinatal infections. Bacteria, like group B streptococci, are a major cause of placental membrane infections leading to prematurity. Understanding the environmental milieu of pregnancy in the reproductive canal is critical to understanding the factors important in prematurity. In addition, a clear understanding of the microbial factors important for successful infection of the placental membranes and the in utero compartment, specifically the amniotic fluid cavity and the fetus, is involved. Scientific approaches include genomic, proteomic, and in vitro and in vivo models of infection. Microbiological methods are utilized to investigate the changing microbial environment of the reproductive system during pregnancy.
The forth focus of this REA involves identifying and testing new clinical therapies and/or prevention strategies to improve the outcome of congenital and perinatal infections. This focus utilizes clinical investigation techniques to prevent HIV infection, bacterial infections, or treatment of congenital infections--such as CMV--to improve infant outcomes. The development of new immunization practices involving the pregnant host has recently been added to this focus.
In collaboration with members of the CHDD, Seattle Children’s Hospital’s Office for Preventing Prematurity and Stillbirth is conducting a two-part initiative funded by the Bill and Melinda Gates Foundation, comprised of: 1) identifying published and unpublished data, and performing a gap analysis on the current status of preterm and stillbirths around the world, and 2) hosting an international summit, which will be held in Seattle in 2009, organized by Seattle Children’s and funded in part by the Gates Foundation. The project and summit are coordinated efforts that build upon a strong foundation of collaboration and partnerships between Seattle Children’s Hospital and the Departments of Pediatrics, Obstetrics and Gynecology, and Global Health at the University of Washington. The goal is to identify common themes many of which involve infectious etiologies, relevant to stillbirths and preterm births to identify opportunities to advance our understanding of this global public health crisis. This effort is a collaborative undertaking by multiple investigators from around the world who have specific investigational expertise in countries heavily impacted by preterm labor and stillbirth.

Faculty Investigators

Craig Rubens, M.D., Ph.D., Professor, Pediatrics, Coordinator
Kristina Adams Waldorf, M.D., Assistant Professor, Obstetrics and Gynecology
Michael Bamshad, M.D., Professor, Pediatrics
Ed Clark, Ph.D., Professor, Microbiology
Lawrence Corey, M.D., Professor, Laboratory Medicine and Medicine
Karen Edwards, Ph.D., Associate Professor, Epidemiology
Jan Englund, M.D., Associate Professor, Pediatrics
David Eschenbach, M.D., Professor and Chair, Obstetrics and Gynecology
David Fredricks, M.D., Associate Professor, Medicine
Adam Geballe, M.D., Professor, Medicine
Chris Gleason, M.D., Professor, Pediatrics
Michael Gravett, M.D., Professor, Obstetrics and Gynecology
Tom Hansen, M.D., Professor, Pediatrics
William Henderson, M.D., Professor, Medicine
Sandra Juul, M.D., Ph.D., Associate Professor, Neonatology
John McGuire, M.D., Assistant Professor, Pediatrics
Ann Melvin, M.D., M.P.H., Associate Professor, Pediatrics
J. Lee Nelson, M.D., Professor, Medicine
William Parks, Ph.D., Professor, Medicine
Dorothy Patton, Ph.D., Professor, Obstetrics and Gynecology
Lakshmi Rajagopal, PhD., Assistant Professor, Pediatrics
David Rawlings, M.D., Associate Professor, Pediatrics
Charles “Skip” Smith, Ph.D., Professor, Pediatrics
Christopher Wilson, M.D., Professor and Chair, Immunology; Professor, Pediatrics
Mark Wurfel, M.D., Ph.D., Assistant Professor, Medicine

University of Washington • Center on Human Development and Disability Box 357920 • Seattle WA 98195-7920 USA • 206-543-7701 •chdd@u.washington.edu