Research Highlights
The research focus of the Division continues to be on major infectious disease pathogens including herpes simplex virus (HSV), cytomegalovirus (CMV), influenza virus, rotavirus, Norovirus, and bioterrorism pathogens. A fundamental goal of ongoing research is to translate basic science and animal model findings into prevention and treatment strategies that can improve human health. Below we highlight a few of the many accomplishments of the division.
Clinical/Translational Research: The rotavirus vaccine, developed by Drs. Ward and Bernstein is now licensed in over 80 countries. The Rotarix" vaccine was also prequalified by the WHO, the first for any rotavirus vaccine. This is a significant advance for the accessibility of rotavirus vaccine for developing countries. The availability of this vaccine could eventually save 500,000 lives per year around the world. Evaluation of vaccines for potential bioterrorism agents and newly emerging pathogens such as avian influenza also continued. Multicenter studies of avian influenza vaccines led by Drs. Bernstein and Brady were promising and identified a vakluable adjuvant that increased iommune responsivieness. With the addition of Dr. Subbramanian these evaluations were extended to include determination of cell mediated responses and an examination of shared influenza T cell epitopes. Preclinical studies funded through our NIH contract to evaluate antivirals led by Drs. Cardin and Bernstein have identified promising microbicides and treatments for herpes virus infections. Epidemiologic research led by Dr. Staat included a CDC funded agreement, which established CCHMC as a sentinel site in surveillance for rotavirus and respiratory pathogens. This work is helping to more accurately determine the health burden of these vaccine preventable diseases and assessing the impact of the national immunization program. Research conducted through our International Adoption Center directed by Dr. Staat provided evidence-based data that will improve the care of adopted children.
The Infection Control Program under the direction of Dr. Connelly played a major role in e quality improvement reducing central line associated bacteremias, surgical site infections, and ventilator associated pneumonias.
This year also saw the recruitment of Dr. Steinhoff, who will lead the Center for Global health. His research interest in global vaccines will allow us to immediately extend our vaccine and epidemiologic studies to international arenas. The recruitment of Dr. Stadler, our former ID felow, to both the ID and Hematology/Oncology divisions, will improve the care we provide to immunocompromised children and extend our research efforts.
Basic Research: The ability of herpes simplex virus to remain latent in the nervous system and periodically reactivate to produce infectious viral progeny lies at the heart of its pathogenic potential and mechanism of transmission. Research in Dr. Sawtell's laboratory has led to critical new insights into the mechansisms of repression and activation of key viral promoters within the context of the latent viral genome in sensory neurons in vivo. In addition, new insights into novel viral strategies for manipulating host defense have been identified.
To determine the role of the Cytomegalovirus-encoded viral chemokine receptor homologs in CMV dissemination Dr. Cardin has identified CC chemokines that enhance the migration or chemotaxis of CMV infected monocytes, the major cell type for CMV latency. These studies contributed new information on the role of the viral chemokine receptors during CMV infection. Dr. Cardin is also currently characterizing the role of chemokines and CMV-infected monocytes as risk factors for atherosclerosis, and pneumonia following bone marrow transplantation.
The team led by Dr. Jiang has continued to characterize the host-pathogen interaction and receptors of Noroviruses. They significantly advanced our understanding of receptor binding interfaces by resolving the atomic structures of the viral capsids. They also identified a new subviral particle, the P particle,with the same receptor binding activities and antigenicity as the viral like particles. Thus, the P particle may be a candidate vaccine or therapeutic becasue they are easy to produce and highly stable. Furthermore, they have identified many compounds which can block noroviruses binding and therefore could be developed as antivirals..
Dr. Strasser's work provided important new information on the pathogenesis of hemolytic uremic syndrome and the Shiga like toxins of E. coli O157 that contruibute to this disease.
Clinical Care: Under the direction of Dr. Gerber the number of inpatient consultations reached new highs as did the number of families using our International Adoption Center directed by Dr. Staat . We continue to be a valuable resource for local pediatricians as demonstrated by the number of priority link calls answered by our faculty.
