Pediatric Infectious Diseases and Immunology Research

Mark R. Schleiss, MD

With respect to the research program of Dr. Schleiss, his basic science clinical work is broadly devoted to the study of human and animal cytomegaloviruses. Congenital infection with CMV is a major public health problem in the United States today, and is responsible for substantial morbidity in newborns. Dr. Schleiss has NIH and March of Dimes funding to pursue studies of the biology of CMV in three major areas: vaccines, immunopathogenesis, and placental infection. One grant focuses on testing hypotheses about vaccine-mediated protection against congenital CMV infection. Using a variety of vaccine expression strategies, including purified protein subunit and DNA vaccines, his lab is evaluating the extent of protection of the maternal-placental-fetal unit against CMV infection and disease, using animal models. These studies integrate molecular virology (cloning and gene expression) with immunological endpoints (humoral and cell-mediated immunity) to attempt to understand in greater detail the aspects of the maternal immune response that are critical in protection of the fetus. Major humoral immune targets include the viral envelope glycoproteins. The second area of research is to study viral immune modulation genes as they relate to the biology and pathogenesis of CMV infection in vivo. CMVs are remarkable in encoding a plethora of putative immune modulation genes, including homologs of cellular G-protein coupled receptor, chemokines, and cytokines. The role of these genes in the in vivo pathogenesis of infection is unclear. Using a molecular genetic approach, Dr. Schleiss, in collaboration with Dr. McGregor, has developed techniques, using viral genomes cloned as infectious bacterial artificial chromosomes (BACs) in E. coli, to perform targeted mutagenesis of viral genes. Systemic mutagenesis of viral immune modulation genes will allow assessment of their function in inflammation, transplacental transmission, and immune evasion. In the third area of research currently being conducted in Dr. Schleiss’s lab, Dr. Schleiss is examining the patterns of transcriptional dysregulation induced following cytomegalovirus infection of placental trophoblasts. Microarray analysis is being performed to test the hypothesis that viral immune modulation genes are responsible for alterations in trophoblast genetic programming, which in turn may facilitate viral transmission to the fetus.

Patricia Ferrieri, MD

Dr. Ferrieri’s research emphasis has been in the following areas: the pathogenesis of infections with group B streptococci (GBS) and host immunity to streptococcal antigens, specifically surface-localized proteins. Earlier research focused on the isolation, biochemical, and immunological characterization of GBS antigens and human and animal immune responses to these antigens and the role of antibodies in protection against infection, as studied in animal models of neonatal sepsis and meningitis. Other studies during this period have included novel approaches in the typing of nontypeable isolates of group B streptococci and molecular characterization of them with recent, additional polysaccharide biochemical characterization carried out in collaboration with the Channing Laboratory, Harvard Medical School. Molecular epidemiological work has continued with the application of pulsed-field gel electrophoresis (PFGE) to nontypeable GBS as well as defined serotypes of established polysaccharide capsule. A new rapid PFGE method for group B Streptococcus isolates has been described from her laboratory, as well as improved methods to upregulate capsular polysaccharide of putative nontypeable GBS isolates from epidemiological studies. The studies of Dr. Ferrieri and others of the surface-localized proteins have particular translational value because of the consideration of conjugating these proteins to purified GBS polysaccharides for vaccine development.

Edward L. Kaplan, MD

Dr. Kaplan is Professor in the Divisions of Pediatric Infectious Disease and of Pediatric Cardiology, and is an internationally recognized authority in his field. As Head of the World Health Organization Collaborating Center for Reference and Research on Streptococci, Dr. Kaplan is primarily interested in the study of group A streptococcal infections and their sequelae. Currently, the laboratory addresses the epidemiology, microbiology, immunology of group A streptococcal applied research. Laboratory opportunities have concentrated on understanding more comprehensively the shifting prevalence of group A streptococcal strains and their M serotypes (emm types when genotyped) by correlation of classical laboratory techniques for characterizing group A streptococci with newer molecular techniques, such as using DNA sequencing of the N terminus or variable region of the M protein. His laboratory is an active participant in an international network of reference laboratories focusing on group A streptococcal infections as well as their sequelae. Currently, active clinical laboratory collaborations between his laboratory and other countries include those in Europe, Eastern Europe, Asia, Egypt, North Africa, and South America. A program to further delineate possible genetic predisposition to development of rheumatic fever has been carried out in collaboration with the Post-graduate Institute for Medical Education and Research in India. With these major collaborations, his laboratory has received many post-graduate students for training in applied research and laboratory techniques. Some of our trainees who have studied in his laboratory have coordinated their research training with obtaining a Master’s Degree in the School of Public Health. In collaboration with the University of Rochester, the lab focuses on tic disorder or obsessive-compulsive disorders occurring in associated with streptococcal infection