Candida albicans is an important cause of invasive infections in the premature neonate. Although the neonate is generally considered as an immunocompromised host, the mechanisms of anti-fungal host defense are poorly defined. Specific antibodies have a role in cell mediated resistance to infection. The long range goal of this proposal is to understand the mechanisms by which specific antibodies may augment host resistance to Candida infection in the immunocompromised neonate. These studies should provide the basis for the development of reagents suitable for passive immunization and additional therapies for these serious infections in patients at risk. The principal investigator is in the first year of a faculty appointment in Pediatrics at Brown University. He earned his M.D. and his Ph.D. in microbiology from the University of Rochester and completed his clinical training as a neonatologist. His graduate and fellowship research was focused on mechanisms of microbial pathogenesis from the perspective of the microbe, and his mentors were basic scientists. This proposal addresses antimicrobial mechanisms from the perspective of the neonatal host. The goals of this sponsored award are twofold. The primary aim is to take advantage of the rich research and training environment at Brown University and its connections with the greater New England region to gain experience in immunobiology. This goal will be achieved through coursework, seminars, and direct mentoring of the research plan with successful and established immunologists.
The second aim i s to gain expertise in the challenges of maturing as a physician-scientist through a close and sustained interaction in a mentored relationship. The structure and personnel included in this proposal will support the candidate in his long term goal of becoming an established scientist focused on the population to whom he has made his clinical commitment as a physician. As such, he will be in an ideal position to orchestrate the translation of basic science to the benefit of patients.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Clinical Investigator Award (CIA) (K08)
Project #
5K08AI064919-04
Application #
7356464
Study Section
Microbiology and Infectious Diseases B Subcommittee (MID)
Program Officer
Duncan, Rory A
Project Start
2005-03-15
Project End
2009-02-28
Budget Start
2008-03-01
Budget End
2009-02-28
Support Year
4
Fiscal Year
2008
Total Cost
$102,600
Indirect Cost
Name
Women and Infants Hospital-Rhode Island
Department
Type
DUNS #
069851913
City
Providence
State
RI
Country
United States
Zip Code
02905
Al-Rawi, Nada; Laforce-Nesbitt, Sonia S; Bliss, Joseph M (2010) Deletion of Candida albicans SPT6 is not lethal but results in defective hyphal growth. Fungal Genet Biol 47:288-96
Linden, Jennifer R; Maccani, Matthew A; Laforce-Nesbitt, Sonia S et al. (2010) High efficiency opsonin-independent phagocytosis of Candida parapsilosis by human neutrophils. Med Mycol 48:355-64
Destin, Kisha G; Linden, Jennifer R; Laforce-Nesbitt, Sonia S et al. (2009) Oxidative burst and phagocytosis of neonatal neutrophils confronting Candida albicans and Candida parapsilosis. Early Hum Dev 85:531-5
Laforce-Nesbitt, Sonia S; Sullivan, Mark A; Hoyer, Lois L et al. (2008) Inhibition of Candida albicans adhesion by recombinant human antibody single-chain variable fragment specific for Als3p. FEMS Immunol Med Microbiol 54:195-202
Bliss, Joseph M; Laforce-Nesbitt, Sonia S (2006) Toxicity to Candida albicans mediated by human serum and peripheral blood mononuclear cells. FEMS Immunol Med Microbiol 46:452-60